S1313, PEGPH20 in Treating Patients With Newly Diagnosed Metastatic Pancreatic Cancer
Sponsor
Southwest Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01959139
Collaborator
National Cancer Institute (NCI) (NIH), Halozyme Therapeutics (Industry)
126
154
3
101.9
0.8
0
Study Details
Study Description
Brief Summary
This partially randomized phase I/II trial studies the side effects and best dose of pegylated recombinant human hyaluronidase (PEGPH20) when given together with combination chemotherapy and to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed pancreatic cancer that has spread to other places in the body. Pegylated recombinant human hyaluronidase may help chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether combination chemotherapy is more effective with or without pegylated recombinant human hyaluronidase in treating pancreatic cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To assess the safety of modified leucovorin calcium, fluorouracil, irinotecan hydrochloride and oxaliplatin (mFOLFIRINOX) in combination with PEGPH20 and select the optimal dose of PEGPH20 for the phase II portion in patients with metastatic pancreatic adenocarcinoma. (Phase I) II. To assess the overall survival of patients with metastatic pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with mFOLFIRINOX alone. (Phase II)
SECONDARY OBJECTIVES:
-
To assess progression free survival (PFS) in patients receiving mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population.
-
To assess objective tumor response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population.
-
To determine the frequency, severity, and tolerability of adverse events of mFOLFIRINOX with PEGPH20.
TERTIARY OBJECTIVES:
-
To explore the correlation of maximum decrease in cancer antigen (CA) 19-9 levels and time to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response.
-
To explore the correlation of plasma hyaluronan (HA) and tumor expression of HA with overall survival, progression-free survival and response.
OUTLINE: This is a phase I, dose de-escalation study of pegylated recombinant human hyaluronidase followed by a randomized phase II study.
PHASE I: Patients receive pegylated recombinant human hyaluronidase intravenously (IV) over 10 minutes on day 1*; oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2; and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and fluorouracil IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pegylated recombinant human hyaluronidase IV over 10 minutes on day 1* and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and fluorouracil as in Arm
- Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
*NOTE: Some patients also receive pegylated recombinant human hyaluronidase on day 3 or 4 of courses 1 and 2.
After completion of study treatment, patients are followed up for 3 years.
Study Design
Study Type:
Interventional
Actual Enrollment
:
126 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
S1313, A Phase IB/II Randomized Study of Modified FOLFIRINOX + Pegylated Recombinant Human Hyaluronidase (PEGPH20) Versus Modified FOLFIRINOX Alone in Patients With Good Performance Status Metastatic Pancreatic Adenocarcinoma
Study Start Date
:
Jan 1, 2014
Actual Primary Completion Date
:
Apr 1, 2019
Anticipated Study Completion Date
:
Jul 1, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Phase II: mFOLFIRINOX Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. |
Drug: Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
Other Names:
Drug: Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
Other Names:
Drug: Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
Other Names:
Drug: 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours
Other Names:
|
| Experimental: Phase II: mFOLFIRINOX + PEGPH20 Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. |
Drug: PEGPH20
3 ug/kg on Day 1, IV over 15 minutes
Other Names:
Drug: Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
Other Names:
Drug: Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
Other Names:
Drug: Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
Other Names:
Drug: 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours
Other Names:
|
| Experimental: Phase I PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours |
Drug: PEGPH20
3 ug/kg on Day 1, IV over 15 minutes
Other Names:
Drug: Oxaliplatin
85 mg/m^2, on Day 2, IV over 2 hours
Other Names:
Drug: Leucovorin
400 mg/m^2, on Day 2, IV over 2 hours
Other Names:
Drug: Irinotecan
180 mg/m^2, on Day 2, IV over 1.5 hours
Other Names:
Drug: 5-fluorouracil
2,400 mg/m^2, Days 2-4, IV over 46 hours
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX [2 cycles of 14 days]
Assess safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion. MTD of PEGPH20 in combination with mFOLFORINOX was evaluated by testing decreasing doses of PEGPH20 from 3mcg/kg on Day 1 and Day 3/4, to 3mcg/kg on Day 1 only and to 1.6 mcg/kg on Day 1 only. MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 17%. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 4 absolute neutrophil count (ANC) anemia or thrombocytopenia; grade 4 ANC lasting > 7 days; grade ≥ 3 febrile neutropenia; grade ≥ 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), total bilirubin, and creatinine; delay in starting the 2nd cycle of mFOLFIRINOX by > 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4. Note: the third and lowest dose level was not reached.
- Phase II: Overall Survival [From date of registration to date of death due to any cause, assessed up to 3 years]
Time from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact. Assessed using the logrank test.
Secondary Outcome Measures
- Progression Free Survival (PFS) (Phase II) [From date of registration to date of death due to any cause, assessed up to 3 years]
Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact.
- Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial) [Up to 3 years]
Objective tumor response rate (complete response, unconfirmed complete response, partial response, unconfirmed partial response) in patients with measurable disease were assessed in each arm and compared between arms using Chi-squared test. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions
- Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [Duration of treatment and follow up until death or 3 years post registration]
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living e.g. bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event
Other Outcome Measures
- Cancer Antigen (CA) 19-9 Levels [Within 2 years of the end of the study]
Explore correlation of maximum decrease in CA 19-9 levels to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response.
- Plasma Expression of Hyaluronan (HA) [Within 2 years of end of study]
- Tumor Expression of HA [Within 2 years of end of study]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
-
Patients must have newly diagnosed, untreated metastatic histologically or cytologically documented pancreatic adenocarcinoma; patients must not have known history of brain metastases
-
Patients must have measurable metastatic disease; computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess measurable disease must have been completed within 28 days prior to registration; CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration; CT scans or MRIs must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
-
Patients must not have had any prior treatment with oxaliplatin or irinotecan within 3 years prior to registration; patients must not have had prior chemotherapy in metastatic setting; prior abdominal radiation therapy is not allowed
-
Patients must have a Zubrod performance status of 0-1
-
Absolute neutrophil count (ANC) >= 1,500/mcL
-
Platelets >= 100,000/mcL
-
Hemoglobin >= 9 g/dL
-
Total bilirubin =< institutional upper limit of normal (IULN)
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 X IULN in the absence of liver metastases or =< 5.0 x IULN with liver metastasis
-
Serum albumin >= 3 g/dL
-
Serum creatinine =< ULN within 14 days prior to registration OR calculated creatinine clearance > 50 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration
-
Patients must have international normalized ratio (INR) =< 1.2 within 14 days prior to registration; patients must not be receiving warfarin for therapeutic use, have history of cerebrovascular accident (CVA), history of transient ischemic attack (TIA) requiring intervention or treatment, pre-existing carotid artery disease requiring intervention or treatment, or current use of megestrol acetate (use within 10 days of registration)
-
Patients must not be receiving chronic treatment (equivalent of prednisone > 10 mg/day) with systemic steroids or other immuno-suppressive agent
-
Patients must not have liver disease such a cirrhosis, chronic active hepatitis or chronic persistent hepatitis
-
Patients must not have active bleeding or a pathological condition that is associated with a high risk of bleeding
-
Patients with a known history of human immunodeficiency virus (HIV) must not be on active treatment for HIV
-
Patients must have no non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
-
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
-
Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
-
Patients must have tumor (paraffin block or slides) available for submission and be willing to submit tumor and blood samples
-
Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
-
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
-
Patients planning to enroll in the phase I portion of this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anchorage Associates in Radiation Medicine | Anchorage | Alaska | United States | 98508 |
| 2 | Alaska Breast Care and Surgery LLC | Anchorage | Alaska | United States | 99508 |
| 3 | Alaska Women's Cancer Care | Anchorage | Alaska | United States | 99508 |
| 4 | Katmai Oncology Group | Anchorage | Alaska | United States | 99508 |
| 5 | Providence Alaska Medical Center | Anchorage | Alaska | United States | 99508 |
| 6 | University of Arizona Cancer Center-North Campus | Tucson | Arizona | United States | 85719 |
| 7 | The University of Arizona Medical Center-University Campus | Tucson | Arizona | United States | 85724 |
| 8 | Sutter Auburn Faith Hospital | Auburn | California | United States | 95602 |
| 9 | Sutter Cancer Centers Radiation Oncology Services-Auburn | Auburn | California | United States | 95603 |
| 10 | Alta Bates Summit Medical Center-Herrick Campus | Berkeley | California | United States | 94704 |
| 11 | Providence Saint Joseph Medical Center/Disney Family Cancer Center | Burbank | California | United States | 91505 |
| 12 | Mills - Peninsula Hospitals | Burlingame | California | United States | 94010 |
| 13 | Sutter Cancer Centers Radiation Oncology Services-Cameron Park | Cameron Park | California | United States | 95682 |
| 14 | Eden Hospital Medical Center | Castro Valley | California | United States | 94546 |
| 15 | City of Hope Corona | Corona | California | United States | 92879 |
| 16 | UC Irvine Health Cancer Center-Newport | Costa Mesa | California | United States | 92627 |
| 17 | Sutter Davis Hospital | Davis | California | United States | 95616 |
| 18 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 19 | Los Angeles County-USC Medical Center | Los Angeles | California | United States | 90033 |
| 20 | USC / Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
| 21 | Fremont - Rideout Cancer Center | Marysville | California | United States | 95901 |
| 22 | Memorial Medical Center | Modesto | California | United States | 95355 |
| 23 | Palo Alto Medical Foundation-Camino Division | Mountain View | California | United States | 94040 |
| 24 | Palo Alto Medical Foundation-Gynecologic Oncology | Mountain View | California | United States | 94040 |
| 25 | Sutter Cancer Research Consortium | Novato | California | United States | 94945 |
| 26 | UC Irvine Health/Chao Family Comprehensive Cancer Center | Orange | California | United States | 92868 |
| 27 | Palo Alto Medical Foundation Health Care | Palo Alto | California | United States | 94301 |
| 28 | Sutter Cancer Centers Radiation Oncology Services-Roseville | Roseville | California | United States | 95661 |
| 29 | Sutter Roseville Medical Center | Roseville | California | United States | 95661 |
| 30 | Sutter General Hospital | Sacramento | California | United States | 95816 |
| 31 | University of California Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 32 | California Pacific Medical Center-Pacific Campus | San Francisco | California | United States | 94115 |
| 33 | Palo Alto Medical Foundation-Santa Cruz | Santa Cruz | California | United States | 95065 |
| 34 | Sutter Pacific Medical Foundation | Santa Rosa | California | United States | 95403 |
| 35 | Palo Alto Medical Foundation-Sunnyvale | Sunnyvale | California | United States | 94086 |
| 36 | Gene Upshaw Memorial Tahoe Forest Cancer Center | Truckee | California | United States | 96161 |
| 37 | Sutter Cancer Centers Radiation Oncology Services-Vacaville | Vacaville | California | United States | 95687 |
| 38 | Sutter Solano Medical Center/Cancer Center | Vallejo | California | United States | 94589 |
| 39 | City of Hope West Covina | West Covina | California | United States | 91790 |
| 40 | Smilow Cancer Hospital-Derby Care Center | Derby | Connecticut | United States | 06418 |
| 41 | Smilow Cancer Hospital Care Center-Fairfield | Fairfield | Connecticut | United States | 06824 |
| 42 | Medical Oncology and Hematology Group PC-Guilford | Guilford | Connecticut | United States | 06437 |
| 43 | Smilow Cancer Hospital Care Center at Saint Francis | Hartford | Connecticut | United States | 06105 |
| 44 | Smilow Cancer Center/Yale-New Haven Hospital | New Haven | Connecticut | United States | 06510 |
| 45 | Yale University | New Haven | Connecticut | United States | 06520 |
| 46 | Yale-New Haven Hospital North Haven Medical Center | North Haven | Connecticut | United States | 06473 |
| 47 | Smilow Cancer Hospital-Orange Care Center | Orange | Connecticut | United States | 06477 |
| 48 | Charlotte Hungerford Hospital Center for Cancer Care | Torrington | Connecticut | United States | 06790 |
| 49 | Smilow Cancer Hospital Care Center-Trumbull | Trumbull | Connecticut | United States | 06611 |
| 50 | Smilow Cancer Hospital-Waterbury Care Center | Waterbury | Connecticut | United States | 06708 |
| 51 | Saint Luke's Mountain States Tumor Institute | Boise | Idaho | United States | 83712 |
| 52 | Saint Luke's Mountain States Tumor Institute - Fruitland | Fruitland | Idaho | United States | 83619 |
| 53 | Saint Luke's Mountain States Tumor Institute - Meridian | Meridian | Idaho | United States | 83642 |
| 54 | Saint Luke's Mountain States Tumor Institute - Nampa | Nampa | Idaho | United States | 83686 |
| 55 | Saint Luke's Mountain States Tumor Institute-Twin Falls | Twin Falls | Idaho | United States | 83301 |
| 56 | Saint Joseph Medical Center | Bloomington | Illinois | United States | 61701 |
| 57 | Illinois CancerCare-Bloomington | Bloomington | Illinois | United States | 61704 |
| 58 | Illinois CancerCare-Canton | Canton | Illinois | United States | 61520 |
| 59 | Memorial Hospital of Carbondale | Carbondale | Illinois | United States | 62902 |
| 60 | Illinois CancerCare-Carthage | Carthage | Illinois | United States | 62321 |
| 61 | Centralia Oncology Clinic | Centralia | Illinois | United States | 62801 |
| 62 | Cancer Care Center of Decatur | Decatur | Illinois | United States | 62526 |
| 63 | Decatur Memorial Hospital | Decatur | Illinois | United States | 62526 |
| 64 | Crossroads Cancer Center | Effingham | Illinois | United States | 62401 |
| 65 | Illinois CancerCare-Eureka | Eureka | Illinois | United States | 61530 |
| 66 | Illinois CancerCare-Galesburg | Galesburg | Illinois | United States | 61401 |
| 67 | Western Illinois Cancer Treatment Center | Galesburg | Illinois | United States | 61401 |
| 68 | Illinois CancerCare-Kewanee Clinic | Kewanee | Illinois | United States | 61443 |
| 69 | Illinois CancerCare-Macomb | Macomb | Illinois | United States | 61455 |
| 70 | Illinois CancerCare-Ottawa Clinic | Ottawa | Illinois | United States | 61350 |
| 71 | Radiation Oncology of Northern Illinois | Ottawa | Illinois | United States | 61350 |
| 72 | Illinois CancerCare-Pekin | Pekin | Illinois | United States | 61554 |
| 73 | OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center | Pekin | Illinois | United States | 61554 |
| 74 | Methodist Medical Center of Illinois | Peoria | Illinois | United States | 61603 |
| 75 | Illinois CancerCare-Peoria | Peoria | Illinois | United States | 61615 |
| 76 | OSF Saint Francis Radiation Oncology at Peoria Cancer Center | Peoria | Illinois | United States | 61615 |
| 77 | OSF Saint Francis Medical Center | Peoria | Illinois | United States | 61637 |
| 78 | Illinois CancerCare-Peru | Peru | Illinois | United States | 61354 |
| 79 | Valley Radiation Oncology | Peru | Illinois | United States | 61354 |
| 80 | Illinois CancerCare-Princeton | Princeton | Illinois | United States | 61356 |
| 81 | Central Illinois Hematology Oncology Center | Springfield | Illinois | United States | 62702 |
| 82 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 83 | Springfield Clinic | Springfield | Illinois | United States | 62702 |
| 84 | Memorial Medical Center | Springfield | Illinois | United States | 62781 |
| 85 | Cancer Care Specialists of Illinois-Swansea | Swansea | Illinois | United States | 62226 |
| 86 | Kansas Institute of Medicine Cancer and Blood Center | Lenexa | Kansas | United States | 66219 |
| 87 | Minimally Invasive Surgery Hospital | Lenexa | Kansas | United States | 66219 |
| 88 | Menorah Medical Center | Overland Park | Kansas | United States | 66209 |
| 89 | Saint Luke's South Hospital | Overland Park | Kansas | United States | 66213 |
| 90 | Kansas City NCI Community Oncology Research Program | Prairie Village | Kansas | United States | 66208 |
| 91 | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
| 92 | Weisberg Cancer Treatment Center | Farmington Hills | Michigan | United States | 48334 |
| 93 | Parkland Health Center-Bonne Terre | Bonne Terre | Missouri | United States | 63628 |
| 94 | Saint Francis Medical Center | Cape Girardeau | Missouri | United States | 63703 |
| 95 | Southeast Cancer Center | Cape Girardeau | Missouri | United States | 63703 |
| 96 | Centerpoint Medical Center LLC | Independence | Missouri | United States | 64057 |
| 97 | Capital Region Medical Center-Goldschmidt Cancer Center | Jefferson City | Missouri | United States | 65109 |
| 98 | Saint Luke's Hospital of Kansas City | Kansas City | Missouri | United States | 64111 |
| 99 | Heartland Hematology and Oncology Associates Incorporated | Kansas City | Missouri | United States | 64118 |
| 100 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
| 101 | Saint Luke's East - Lee's Summit | Lee's Summit | Missouri | United States | 64086 |
| 102 | Liberty Radiation Oncology Center | Liberty | Missouri | United States | 64068 |
| 103 | Heartland Regional Medical Center | Saint Joseph | Missouri | United States | 64506 |
| 104 | Missouri Baptist Medical Center | Saint Louis | Missouri | United States | 63131 |
| 105 | Sainte Genevieve County Memorial Hospital | Sainte Genevieve | Missouri | United States | 63670 |
| 106 | Missouri Baptist Sullivan Hospital | Sullivan | Missouri | United States | 63080 |
| 107 | Missouri Baptist Outpatient Center-Sunset Hills | Sunset Hills | Missouri | United States | 63127 |
| 108 | Randolph Hospital | Asheboro | North Carolina | United States | 27203 |
| 109 | Cone Health Cancer Center at Alamance Regional | Burlington | North Carolina | United States | 27215 |
| 110 | Southeastern Medical Oncology Center-Clinton | Clinton | North Carolina | United States | 28328 |
| 111 | Southeastern Medical Oncology Center-Goldsboro | Goldsboro | North Carolina | United States | 27534 |
| 112 | Wayne Memorial Hospital | Goldsboro | North Carolina | United States | 27534 |
| 113 | Cone Health Cancer Center | Greensboro | North Carolina | United States | 27403 |
| 114 | Hendersonville Hematology and Oncology at Pardee | Hendersonville | North Carolina | United States | 28791 |
| 115 | Margaret R Pardee Memorial Hospital | Hendersonville | North Carolina | United States | 28791 |
| 116 | Southeastern Medical Oncology Center-Jacksonville | Jacksonville | North Carolina | United States | 28546 |
| 117 | Cone Heath Cancer Center at Mebane | Mebane | North Carolina | United States | 27302 |
| 118 | Annie Penn Memorial Hospital | Reidsville | North Carolina | United States | 27320 |
| 119 | Southeastern Medical Oncology Center-Wilson | Wilson | North Carolina | United States | 27893 |
| 120 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 121 | Saint Charles Health System | Bend | Oregon | United States | 97701 |
| 122 | Clackamas Radiation Oncology Center | Clackamas | Oregon | United States | 97015 |
| 123 | Providence Oncology and Hematology Care Southeast | Clackamas | Oregon | United States | 97015 |
| 124 | Bay Area Hospital | Coos Bay | Oregon | United States | 97420 |
| 125 | Providence Newberg Medical Center | Newberg | Oregon | United States | 97132 |
| 126 | Providence Willamette Falls Medical Center | Oregon City | Oregon | United States | 97045 |
| 127 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
| 128 | Providence Saint Vincent Medical Center | Portland | Oregon | United States | 97225 |
| 129 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 130 | Providence Regional Cancer System-Aberdeen | Aberdeen | Washington | United States | 98520 |
| 131 | Cancer Care Center at Island Hospital | Anacortes | Washington | United States | 98221 |
| 132 | PeaceHealth Saint Joseph Medical Center | Bellingham | Washington | United States | 98225 |
| 133 | Providence Regional Cancer System-Centralia | Centralia | Washington | United States | 98531 |
| 134 | Swedish Medical Center-Edmonds | Edmonds | Washington | United States | 98026 |
| 135 | Providence Regional Cancer Partnership | Everett | Washington | United States | 98201 |
| 136 | Swedish Cancer Institute-Issaquah | Issaquah | Washington | United States | 98029 |
| 137 | Kadlec Clinic Hematology and Oncology | Kennewick | Washington | United States | 99336 |
| 138 | Seattle Cancer Care Alliance at EvergreenHealth | Kirkland | Washington | United States | 98034 |
| 139 | Providence Regional Cancer System-Lacey | Lacey | Washington | United States | 98503 |
| 140 | PeaceHealth Saint John Medical Center | Longview | Washington | United States | 98632 |
| 141 | Minor and James Medical PLLC | Seattle | Washington | United States | 98104 |
| 142 | Pacific Gynecology Specialists | Seattle | Washington | United States | 98104 |
| 143 | Swedish Medical Center-Ballard Campus | Seattle | Washington | United States | 98107 |
| 144 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109 |
| 145 | Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109 |
| 146 | Group Health Cooperative-Seattle | Seattle | Washington | United States | 98112 |
| 147 | Swedish Medical Center-First Hill | Seattle | Washington | United States | 98122-4307 |
| 148 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
| 149 | Providence Regional Cancer System-Shelton | Shelton | Washington | United States | 98584 |
| 150 | Rockwood Clinic Cancer Treatment Center-Valley | Spokane Valley | Washington | United States | 99216 |
| 151 | Rockwood Cancer Treatment Center-DHEC-Downtown | Spokane | Washington | United States | 99204 |
| 152 | PeaceHealth Southwest Medical Center | Vancouver | Washington | United States | 98664 |
| 153 | Providence Saint Mary Regional Cancer Center | Walla Walla | Washington | United States | 99362 |
| 154 | Providence Regional Cancer System-Yelm | Yelm | Washington | United States | 98597 |
Sponsors and Collaborators
- Southwest Oncology Group
- National Cancer Institute (NCI)
- Halozyme Therapeutics
Investigators
- Study Chair: Ramesh K Ramanathan, M.D., Virginia G. Piper Cancer Center
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01959139
Other Study ID Numbers:
- S1313
- NCI-2013-01776
- U10CA180888
- S1313
First Posted:
Oct 9, 2013
Last Update Posted:
Dec 1, 2021
Last Verified:
Nov 1, 2021
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 126 participants were enrolled to this study, however, 1 withdrew consent and 3 were ineligible. |
| Arm/Group Title | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: mFOLFIRINOX + PEGPH20 |
|---|---|---|---|---|
| Arm/Group Description | PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours | PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours |
| Period Title: Phase I: Cohort 1 | ||||
| STARTED | 5 | 0 | 0 | 0 |
| COMPLETED | 5 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: Phase I: Cohort 1 | ||||
| STARTED | 0 | 6 | 0 | 0 |
| COMPLETED | 0 | 6 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: Phase I: Cohort 1 | ||||
| STARTED | 0 | 0 | 56 | 55 |
| Assessed for AEs | 0 | 0 | 54 | 51 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 56 | 55 |
Baseline Characteristics
| Arm/Group Title | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: mFOLFIRINOX + PEGPH20 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours | PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Total of all reporting groups |
| Overall Participants | 5 | 6 | 56 | 55 | 122 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
65.4
|
60.2
|
60.5
|
63.9
|
62.2
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
60%
|
2
33.3%
|
25
44.6%
|
31
56.4%
|
61
50%
|
| Male |
2
40%
|
4
66.7%
|
31
55.4%
|
24
43.6%
|
61
50%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
16.7%
|
4
7.1%
|
7
12.7%
|
12
9.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
20%
|
1
16.7%
|
4
7.1%
|
1
1.8%
|
7
5.7%
|
| White |
3
60%
|
4
66.7%
|
46
82.1%
|
43
78.2%
|
96
78.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
20%
|
0
0%
|
2
3.6%
|
4
7.3%
|
7
5.7%
|
| Zubrod performance status (Count of Participants) | |||||
| 0 |
2
40%
|
5
83.3%
|
31
55.4%
|
32
58.2%
|
70
57.4%
|
| 1 |
3
60%
|
1
16.7%
|
25
44.6%
|
23
41.8%
|
52
42.6%
|
| Primary site (Count of Participants) | |||||
| Head of pancreas |
2
40%
|
4
66.7%
|
16
28.6%
|
19
34.5%
|
41
33.6%
|
| Body of pancreas |
1
20%
|
0
0%
|
16
28.6%
|
16
29.1%
|
33
27%
|
| Tail of pancreas |
2
40%
|
1
16.7%
|
15
26.8%
|
11
20%
|
29
23.8%
|
| Pancreas, NOS |
0
0%
|
1
16.7%
|
9
16.1%
|
9
16.4%
|
19
15.6%
|
| Sites of involvement (Count of Participants) | |||||
| Primary tumor/pancreas |
4
80%
|
4
66.7%
|
51
91.1%
|
49
89.1%
|
108
88.5%
|
| Regional lymph nodes |
3
60%
|
3
50%
|
22
39.3%
|
16
29.1%
|
44
36.1%
|
| Distant lymph nodes |
0
0%
|
3
50%
|
6
10.7%
|
5
9.1%
|
14
11.5%
|
| Lung |
1
20%
|
1
16.7%
|
18
32.1%
|
14
25.5%
|
34
27.9%
|
| Liver |
4
80%
|
3
50%
|
45
80.4%
|
42
76.4%
|
94
77%
|
| Peritoneum |
1
20%
|
1
16.7%
|
12
21.4%
|
11
20%
|
25
20.5%
|
| Other |
1
20%
|
1
16.7%
|
12
21.4%
|
9
16.4%
|
23
18.9%
|
| Serum cancer antigen (CA) 19-9 (Count of Participants) | |||||
| < 37 |
1
20%
|
1
16.7%
|
10
17.9%
|
7
12.7%
|
19
15.6%
|
| >= 37 |
4
80%
|
5
83.3%
|
46
82.1%
|
48
87.3%
|
103
84.4%
|
| Prior treatment for pancreatic cancer (Count of Participants) | |||||
| Chemotherapy |
0
0%
|
1
16.7%
|
3
5.4%
|
4
7.3%
|
8
6.6%
|
| Surgery |
0
0%
|
1
16.7%
|
2
3.6%
|
7
12.7%
|
10
8.2%
|
Outcome Measures
| Title | Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX |
|---|---|
| Description | Assess safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion. MTD of PEGPH20 in combination with mFOLFORINOX was evaluated by testing decreasing doses of PEGPH20 from 3mcg/kg on Day 1 and Day 3/4, to 3mcg/kg on Day 1 only and to 1.6 mcg/kg on Day 1 only. MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 17%. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 4 absolute neutrophil count (ANC) anemia or thrombocytopenia; grade 4 ANC lasting > 7 days; grade ≥ 3 febrile neutropenia; grade ≥ 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), total bilirubin, and creatinine; delay in starting the 2nd cycle of mFOLFIRINOX by > 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4. Note: the third and lowest dose level was not reached. |
| Time Frame | 2 cycles of 14 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All analyzable patients who experienced a dose limiting toxicity attributable to PEGPH20 and/or mFOLFIRINOX in the first cycle |
| Arm/Group Title | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 | All Phase 1 Participants |
|---|---|---|---|
| Arm/Group Description | PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours | PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Phase I participants that received PEGPH20 at the assigned dose for cycle 1. |
| Measure Participants | 5 | 6 | 11 |
| Number [ug/kg] |
0
|
3
|
3
|
| Title | Phase II: Overall Survival |
|---|---|
| Description | Time from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact. Assessed using the logrank test. |
| Time Frame | From date of registration to date of death due to any cause, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eligible and analyzable participants |
| Arm/Group Title | Phase II: mFOLFIRINOX | Phase II: mFOLFIRINOX + PEGPH20 |
|---|---|---|
| Arm/Group Description | Participants receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours |
| Measure Participants | 56 | 55 |
| Median (95% Confidence Interval) [months] |
14.4
|
7.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4, Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.01 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 2.07 | |
| Confidence Interval |
(2-Sided) 95% 1.28 to 3.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression Free Survival (PFS) (Phase II) |
|---|---|
| Description | Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Participants last known to be alive without report of progression are censored at date of last contact. |
| Time Frame | From date of registration to date of death due to any cause, assessed up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eligible and analyzable participants |
| Arm/Group Title | Phase II: mFOLFIRINOX | Phase II: mFOLFIRINOX + PEGPH20 |
|---|---|---|
| Arm/Group Description | Participants receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours |
| Measure Participants | 56 | 55 |
| Median (95% Confidence Interval) [months] |
6.2
|
4.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4, Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.01 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.74 | |
| Confidence Interval |
(2-Sided) 95% 1.14 to 2.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial) |
|---|---|
| Description | Objective tumor response rate (complete response, unconfirmed complete response, partial response, unconfirmed partial response) in patients with measurable disease were assessed in each arm and compared between arms using Chi-squared test. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with measurable disease |
| Arm/Group Title | Phase II: mFOLFIRINOX | Phase II: mFOLFIRINOX + PEGPH20 |
|---|---|---|
| Arm/Group Description | Participants receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours 5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours |
| Measure Participants | 56 | 55 |
| Number (95% Confidence Interval) [percent of participants] |
45
900%
|
33
550%
|
| Title | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
|---|---|
| Description | Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living e.g. bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event |
| Time Frame | Duration of treatment and follow up until death or 3 years post registration |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who received at least one dose of protocol treatment. Only 105 participants in the phase II trial were assessed for AEs, as 6 participants did not receive protocol treatment. |
| Arm/Group Title | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: PEGPH20 + mFOLFIRINOX |
|---|---|---|---|---|
| Arm/Group Description | PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes__Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours | PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes__Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.__Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.__PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes__Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours |
| Measure Participants | 5 | 6 | 54 | 51 |
| Abdominal pain |
0
0%
|
0
0%
|
1
1.8%
|
3
5.5%
|
| Acute kidney injury |
1
20%
|
0
0%
|
0
0%
|
0
0%
|
| Alanine aminotransferase increased |
1
20%
|
1
16.7%
|
0
0%
|
3
5.5%
|
| Alkaline phosphatase increased |
0
0%
|
1
16.7%
|
0
0%
|
2
3.6%
|
| Anemia |
0
0%
|
0
0%
|
4
7.1%
|
2
3.6%
|
| Anorexia |
0
0%
|
0
0%
|
2
3.6%
|
3
5.5%
|
| Arthralgia |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Ascites |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Aspartate aminotransferase increased |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Blood bilirubin increased |
1
20%
|
0
0%
|
0
0%
|
1
1.8%
|
| Creatinine increased |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Dehydration |
1
20%
|
1
16.7%
|
7
12.5%
|
4
7.3%
|
| Depression |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Diarrhea |
1
20%
|
0
0%
|
10
17.9%
|
12
21.8%
|
| Esophagitis |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Fatigue |
2
40%
|
1
16.7%
|
6
10.7%
|
11
20%
|
| Febrile neutropenia |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Gallbladder obstruction |
1
20%
|
0
0%
|
0
0%
|
0
0%
|
| Gastrointestinal disorders - Other, specify |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| General disorders and admin site conditions- Other |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Generalized muscle weakness |
0
0%
|
0
0%
|
1
1.8%
|
3
5.5%
|
| Hyperglycemia |
0
0%
|
0
0%
|
1
1.8%
|
1
1.8%
|
| Hypertension |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Hypokalemia |
1
20%
|
1
16.7%
|
3
5.4%
|
4
7.3%
|
| Hyponatremia |
1
20%
|
1
16.7%
|
1
1.8%
|
3
5.5%
|
| Hypophosphatemia |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Hypotension |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
| Infections and infestations - Other, specify |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Infusion related reaction |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Leukocytosis |
0
0%
|
0
0%
|
2
3.6%
|
1
1.8%
|
| Lung infection |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Lymphocyte count decreased |
0
0%
|
0
0%
|
1
1.8%
|
4
7.3%
|
| Mucositis oral |
1
20%
|
0
0%
|
0
0%
|
4
7.3%
|
| Myalgia |
1
20%
|
0
0%
|
0
0%
|
2
3.6%
|
| Nausea |
1
20%
|
0
0%
|
8
14.3%
|
12
21.8%
|
| Neutrophil count decreased |
0
0%
|
0
0%
|
4
7.1%
|
3
5.5%
|
| Pain |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Paresthesia |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Peripheral motor neuropathy |
0
0%
|
0
0%
|
1
1.8%
|
1
1.8%
|
| Peripheral sensory neuropathy |
0
0%
|
2
33.3%
|
2
3.6%
|
5
9.1%
|
| Peritoneal infection |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Platelet count decreased |
0
0%
|
1
16.7%
|
2
3.6%
|
3
5.5%
|
| Portal vein thrombosis |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Pulmonary hypertension |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Resp, thoracic and mediastinal disorders - Other |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Sepsis |
1
20%
|
0
0%
|
1
1.8%
|
1
1.8%
|
| Skin infection |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Small intestine infection |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Spasticity |
0
0%
|
0
0%
|
0
0%
|
1
1.8%
|
| Thromboembolic event |
0
0%
|
0
0%
|
1
1.8%
|
5
9.1%
|
| Ventricular tachycardia |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| Vomiting |
1
20%
|
1
16.7%
|
8
14.3%
|
10
18.2%
|
| Weight loss |
0
0%
|
0
0%
|
1
1.8%
|
0
0%
|
| White blood cell decreased |
0
0%
|
0
0%
|
2
3.6%
|
2
3.6%
|
| Title | Cancer Antigen (CA) 19-9 Levels |
|---|---|
| Description | Explore correlation of maximum decrease in CA 19-9 levels to maximum decrease in CA 19-9 levels with overall survival, progression-free survival and response. |
| Time Frame | Within 2 years of the end of the study |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Plasma Expression of Hyaluronan (HA) |
|---|---|
| Description | |
| Time Frame | Within 2 years of end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Tumor Expression of HA |
|---|---|
| Description | |
| Time Frame | Within 2 years of end of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Duration of treatment and follow up until death or 3 years post registration | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Only 105 participants in the phase II trial were assessed for AEs, as 6 participants did not receive protocol therapy. | |||||||
| Arm/Group Title | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: PEGPH20 + mFOLFIRINOX | ||||
| Arm/Group Description | PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes__Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours | PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes__Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.__Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | Participants receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.__PEGPH20: 3 ug/kg on Day 1, IV over 15 minutes__Oxaliplatin: 85 mg/m^2, on Day 2, IV over 2 hours__Leucovorin: 400 mg/m^2, on Day 2, IV over 2 hours__Irinotecan: 180 mg/m^2, on Day 2, IV over 1.5 hours__5-fluorouracil: 2,400 mg/m^2, Days 2-4, IV over 46 hours | ||||
All Cause Mortality |
||||||||
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: PEGPH20 + mFOLFIRINOX | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 5/6 (83.3%) | 49/56 (87.5%) | 50/55 (90.9%) | ||||
Serious Adverse Events |
||||||||
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: PEGPH20 + mFOLFIRINOX | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/5 (60%) | 4/6 (66.7%) | 9/54 (16.7%) | 36/51 (70.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 2/51 (3.9%) | ||||
| Cardiac disorders | ||||||||
| Cardiac arrest | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Left ventricular systolic dysfunction | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Abdominal pain | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 6/51 (11.8%) | ||||
| Ascites | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Colitis | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Constipation | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 1/51 (2%) | ||||
| Diarrhea | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 7/51 (13.7%) | ||||
| Duodenal obstruction | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Duodenal ulcer | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Dysphagia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Enterocolitis | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Esophagitis | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Gastrointestinal disorders-Other | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Ileus | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Lower gastrointestinal hemorrhage | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Mucositis oral | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Nausea | 2/5 (40%) | 0/6 (0%) | 1/54 (1.9%) | 9/51 (17.6%) | ||||
| Rectal hemorrhage | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Small intestinal obstruction | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Vomiting | 2/5 (40%) | 1/6 (16.7%) | 2/54 (3.7%) | 9/51 (17.6%) | ||||
| General disorders | ||||||||
| Death NOS | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Fatigue | 1/5 (20%) | 1/6 (16.7%) | 0/54 (0%) | 5/51 (9.8%) | ||||
| Fever | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Infusion related reaction | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Pain | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Hepatobiliary disorders | ||||||||
| Gallbladder obstruction | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Hepatobiliary disorders-Other | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Infections and infestations | ||||||||
| Device related infection | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Lung infection | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Peritoneal infection | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Sepsis | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 2/51 (3.9%) | ||||
| Skin infection | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Small intestine infection | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Urinary tract infection | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Alkaline phosphatase increased | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Aspartate aminotransferase increased | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Blood bilirubin increased | 1/5 (20%) | 1/6 (16.7%) | 0/54 (0%) | 1/51 (2%) | ||||
| Lymphocyte count decreased | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Neutrophil count decreased | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Platelet count decreased | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Weight loss | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 2/51 (3.9%) | ||||
| Dehydration | 1/5 (20%) | 1/6 (16.7%) | 0/54 (0%) | 4/51 (7.8%) | ||||
| Hyperglycemia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 2/51 (3.9%) | ||||
| Hypoalbuminemia | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Hypocalcemia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Hypokalemia | 1/5 (20%) | 1/6 (16.7%) | 0/54 (0%) | 3/51 (5.9%) | ||||
| Hyponatremia | 1/5 (20%) | 1/6 (16.7%) | 0/54 (0%) | 2/51 (3.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Generalized muscle weakness | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 3/51 (5.9%) | ||||
| Myalgia | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 1/51 (2%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Neoplasms benign, malignant and unspecified - Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 2/51 (3.9%) | ||||
| Nervous system disorders | ||||||||
| Transient ischemic attacks | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Psychiatric disorders | ||||||||
| Delirium | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Dyspnea | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 3/51 (5.9%) | ||||
| Pneumothorax | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Pulmonary hypertension | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Resp, thoracic and mediastinal disorders - Other | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Thromboembolic event | 1/5 (20%) | 1/6 (16.7%) | 4/54 (7.4%) | 11/51 (21.6%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 and Day 3/4 | Phase I: mFOLFIRINOX + PEGPH20, 3 ug/kg on Day 1 Only | Phase II: mFOLFIRINOX | Phase II: PEGPH20 + mFOLFIRINOX | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/5 (80%) | 6/6 (100%) | 52/54 (96.3%) | 50/51 (98%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 1/5 (20%) | 4/6 (66.7%) | 36/54 (66.7%) | 37/51 (72.5%) | ||||
| Blood and lymphatic system disorders - Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Febrile neutropenia | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Leukocytosis | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 2/51 (3.9%) | ||||
| Cardiac disorders | ||||||||
| Cardiac disorders-Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Chest pain - cardiac | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Palpitations | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Sinus tachycardia | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 3/51 (5.9%) | ||||
| Ventricular tachycardia | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear pain | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 3/51 (5.9%) | ||||
| Hearing impaired | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Vertigo | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Endocrine disorders | ||||||||
| Endocrine disorders-Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Hyperthyroidism | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Hypothyroidism | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Eye disorders | ||||||||
| Blurred vision | 2/5 (40%) | 1/6 (16.7%) | 6/54 (11.1%) | 2/51 (3.9%) | ||||
| Dry eye | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Eye disorders-Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 3/51 (5.9%) | ||||
| Eye pain | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 2/51 (3.9%) | ||||
| Floaters | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/5 (0%) | 1/6 (16.7%) | 2/54 (3.7%) | 2/51 (3.9%) | ||||
| Abdominal pain | 2/5 (40%) | 3/6 (50%) | 27/54 (50%) | 22/51 (43.1%) | ||||
| Anal hemorrhage | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Anal pain | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Ascites | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 2/51 (3.9%) | ||||
| Bloating | 1/5 (20%) | 1/6 (16.7%) | 4/54 (7.4%) | 6/51 (11.8%) | ||||
| Colitis | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Colonic obstruction | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Constipation | 3/5 (60%) | 4/6 (66.7%) | 20/54 (37%) | 16/51 (31.4%) | ||||
| Diarrhea | 4/5 (80%) | 4/6 (66.7%) | 41/54 (75.9%) | 38/51 (74.5%) | ||||
| Dry mouth | 1/5 (20%) | 0/6 (0%) | 2/54 (3.7%) | 5/51 (9.8%) | ||||
| Duodenal ulcer | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Dyspepsia | 1/5 (20%) | 0/6 (0%) | 8/54 (14.8%) | 5/51 (9.8%) | ||||
| Dysphagia | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 4/51 (7.8%) | ||||
| Enterocolitis | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Esophageal pain | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Esophagitis | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Flatulence | 0/5 (0%) | 1/6 (16.7%) | 8/54 (14.8%) | 0/51 (0%) | ||||
| Gastritis | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Gastroesophageal reflux disease | 1/5 (20%) | 1/6 (16.7%) | 1/54 (1.9%) | 3/51 (5.9%) | ||||
| Gastrointestinal disorders-Other | 1/5 (20%) | 0/6 (0%) | 4/54 (7.4%) | 4/51 (7.8%) | ||||
| Gastrointestinal pain | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Gastroparesis | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Hemorrhoidal hemorrhage | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Hemorrhoids | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Mucositis oral | 1/5 (20%) | 1/6 (16.7%) | 10/54 (18.5%) | 11/51 (21.6%) | ||||
| Nausea | 2/5 (40%) | 4/6 (66.7%) | 39/54 (72.2%) | 39/51 (76.5%) | ||||
| Obstruction gastric | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Oral dysesthesia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Oral pain | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 3/51 (5.9%) | ||||
| Rectal hemorrhage | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Small intestinal obstruction | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Stomach pain | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Vomiting | 0/5 (0%) | 1/6 (16.7%) | 26/54 (48.1%) | 23/51 (45.1%) | ||||
| General disorders | ||||||||
| Chills | 0/5 (0%) | 0/6 (0%) | 6/54 (11.1%) | 1/51 (2%) | ||||
| Edema face | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Edema limbs | 2/5 (40%) | 2/6 (33.3%) | 10/54 (18.5%) | 20/51 (39.2%) | ||||
| Edema trunk | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Fatigue | 4/5 (80%) | 5/6 (83.3%) | 42/54 (77.8%) | 40/51 (78.4%) | ||||
| Fever | 0/5 (0%) | 1/6 (16.7%) | 7/54 (13%) | 2/51 (3.9%) | ||||
| Flu like symptoms | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Gait disturbance | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| General disorders and admin site conditions - Other | 0/5 (0%) | 0/6 (0%) | 4/54 (7.4%) | 4/51 (7.8%) | ||||
| Infusion related reaction | 1/5 (20%) | 0/6 (0%) | 7/54 (13%) | 8/51 (15.7%) | ||||
| Localized edema | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Malaise | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 1/51 (2%) | ||||
| Non-cardiac chest pain | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 3/51 (5.9%) | ||||
| Pain | 1/5 (20%) | 2/6 (33.3%) | 12/54 (22.2%) | 10/51 (19.6%) | ||||
| Hepatobiliary disorders | ||||||||
| Portal vein thrombosis | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Immune system disorders | ||||||||
| Allergic reaction | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Infections and infestations | ||||||||
| Bladder infection | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Bronchial infection | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Enterocolitis infectious | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Eye infection | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Hepatic infection | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Infections and infestations-Other | 0/5 (0%) | 0/6 (0%) | 6/54 (11.1%) | 3/51 (5.9%) | ||||
| Mucosal infection | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 2/51 (3.9%) | ||||
| Otitis media | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Pelvic infection | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Pharyngitis | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Sinusitis | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Upper respiratory infection | 0/5 (0%) | 2/6 (33.3%) | 2/54 (3.7%) | 3/51 (5.9%) | ||||
| Urinary tract infection | 0/5 (0%) | 0/6 (0%) | 5/54 (9.3%) | 4/51 (7.8%) | ||||
| Vaginal infection | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Bruising | 1/5 (20%) | 0/6 (0%) | 3/54 (5.6%) | 2/51 (3.9%) | ||||
| Fall | 0/5 (0%) | 0/6 (0%) | 4/54 (7.4%) | 5/51 (9.8%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/5 (40%) | 3/6 (50%) | 18/54 (33.3%) | 19/51 (37.3%) | ||||
| Alkaline phosphatase increased | 2/5 (40%) | 3/6 (50%) | 24/54 (44.4%) | 24/51 (47.1%) | ||||
| Aspartate aminotransferase increased | 2/5 (40%) | 2/6 (33.3%) | 17/54 (31.5%) | 18/51 (35.3%) | ||||
| Blood bilirubin increased | 1/5 (20%) | 0/6 (0%) | 3/54 (5.6%) | 3/51 (5.9%) | ||||
| Creatinine increased | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Electrocardiogram QT corrected interval prolonged | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| GGT increased | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| INR increased | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 2/51 (3.9%) | ||||
| Investigations-Other | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 4/51 (7.8%) | ||||
| Lymphocyte count decreased | 1/5 (20%) | 0/6 (0%) | 8/54 (14.8%) | 7/51 (13.7%) | ||||
| Lymphocyte count increased | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Neutrophil count decreased | 0/5 (0%) | 2/6 (33.3%) | 9/54 (16.7%) | 6/51 (11.8%) | ||||
| Platelet count decreased | 2/5 (40%) | 2/6 (33.3%) | 27/54 (50%) | 22/51 (43.1%) | ||||
| Weight loss | 0/5 (0%) | 3/6 (50%) | 18/54 (33.3%) | 27/51 (52.9%) | ||||
| White blood cell decreased | 1/5 (20%) | 2/6 (33.3%) | 10/54 (18.5%) | 9/51 (17.6%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 3/5 (60%) | 3/6 (50%) | 25/54 (46.3%) | 26/51 (51%) | ||||
| Dehydration | 0/5 (0%) | 1/6 (16.7%) | 15/54 (27.8%) | 6/51 (11.8%) | ||||
| Hypercalcemia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 4/51 (7.8%) | ||||
| Hyperglycemia | 1/5 (20%) | 2/6 (33.3%) | 22/54 (40.7%) | 24/51 (47.1%) | ||||
| Hyperkalemia | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Hypermagnesemia | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Hypernatremia | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Hypertriglyceridemia | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Hypoalbuminemia | 2/5 (40%) | 3/6 (50%) | 24/54 (44.4%) | 26/51 (51%) | ||||
| Hypocalcemia | 0/5 (0%) | 1/6 (16.7%) | 5/54 (9.3%) | 24/51 (47.1%) | ||||
| Hypoglycemia | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 1/51 (2%) | ||||
| Hypokalemia | 1/5 (20%) | 5/6 (83.3%) | 28/54 (51.9%) | 19/51 (37.3%) | ||||
| Hypomagnesemia | 0/5 (0%) | 0/6 (0%) | 6/54 (11.1%) | 4/51 (7.8%) | ||||
| Hyponatremia | 0/5 (0%) | 1/6 (16.7%) | 17/54 (31.5%) | 18/51 (35.3%) | ||||
| Hypophosphatemia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Metabolism and nutrition disorders - Other, specify | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/5 (20%) | 1/6 (16.7%) | 6/54 (11.1%) | 7/51 (13.7%) | ||||
| Arthritis | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Back pain | 2/5 (40%) | 2/6 (33.3%) | 13/54 (24.1%) | 8/51 (15.7%) | ||||
| Bone pain | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Buttock pain | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Chest wall pain | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Flank pain | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 1/51 (2%) | ||||
| Generalized muscle weakness | 1/5 (20%) | 0/6 (0%) | 11/54 (20.4%) | 6/51 (11.8%) | ||||
| Muscle weakness lower limb | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 1/51 (2%) | ||||
| Musculoskeletal and connective tiss disorder - Other | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 6/51 (11.8%) | ||||
| Myalgia | 4/5 (80%) | 3/6 (50%) | 6/54 (11.1%) | 19/51 (37.3%) | ||||
| Pain in extremity | 0/5 (0%) | 1/6 (16.7%) | 3/54 (5.6%) | 4/51 (7.8%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Neoplasms benign, malignant and unspecified - Other | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Nervous system disorders | ||||||||
| Ataxia | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Cognitive disturbance | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Concentration impairment | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Depressed level of consciousness | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Dizziness | 0/5 (0%) | 2/6 (33.3%) | 9/54 (16.7%) | 9/51 (17.6%) | ||||
| Dysarthria | 1/5 (20%) | 0/6 (0%) | 3/54 (5.6%) | 2/51 (3.9%) | ||||
| Dysesthesia | 1/5 (20%) | 0/6 (0%) | 1/54 (1.9%) | 2/51 (3.9%) | ||||
| Dysgeusia | 3/5 (60%) | 3/6 (50%) | 12/54 (22.2%) | 13/51 (25.5%) | ||||
| Facial muscle weakness | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Facial nerve disorder | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Headache | 1/5 (20%) | 2/6 (33.3%) | 9/54 (16.7%) | 5/51 (9.8%) | ||||
| Memory impairment | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Nervous system disorders-Other | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 2/51 (3.9%) | ||||
| Paresthesia | 2/5 (40%) | 0/6 (0%) | 10/54 (18.5%) | 7/51 (13.7%) | ||||
| Peripheral motor neuropathy | 1/5 (20%) | 1/6 (16.7%) | 2/54 (3.7%) | 6/51 (11.8%) | ||||
| Peripheral sensory neuropathy | 4/5 (80%) | 4/6 (66.7%) | 32/54 (59.3%) | 24/51 (47.1%) | ||||
| Presyncope | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Sinus pain | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Spasticity | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Syncope | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Tremor | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 1/51 (2%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/5 (0%) | 1/6 (16.7%) | 10/54 (18.5%) | 5/51 (9.8%) | ||||
| Confusion | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 1/51 (2%) | ||||
| Depression | 0/5 (0%) | 0/6 (0%) | 7/54 (13%) | 4/51 (7.8%) | ||||
| Insomnia | 1/5 (20%) | 2/6 (33.3%) | 9/54 (16.7%) | 10/51 (19.6%) | ||||
| Personality change | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Psychiatric disorders-Other | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Renal and urinary disorders | ||||||||
| Hematuria | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 2/51 (3.9%) | ||||
| Proteinuria | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 2/51 (3.9%) | ||||
| Renal calculi | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Urinary frequency | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Urinary incontinence | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Urinary retention | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Urinary tract obstruction | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Urinary tract pain | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Reproductive system and breast disorders | ||||||||
| Menorrhagia | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Vaginal discharge | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Allergic rhinitis | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Cough | 0/5 (0%) | 1/6 (16.7%) | 6/54 (11.1%) | 6/51 (11.8%) | ||||
| Dyspnea | 0/5 (0%) | 1/6 (16.7%) | 5/54 (9.3%) | 6/51 (11.8%) | ||||
| Epistaxis | 1/5 (20%) | 0/6 (0%) | 5/54 (9.3%) | 3/51 (5.9%) | ||||
| Hiccups | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 4/51 (7.8%) | ||||
| Hoarseness | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 3/51 (5.9%) | ||||
| Laryngopharyngeal dysesthesia | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Nasal congestion | 0/5 (0%) | 1/6 (16.7%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Pleural effusion | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Pleuritic pain | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Pneumonitis | 0/5 (0%) | 1/6 (16.7%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Postnasal drip | 1/5 (20%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Productive cough | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 0/51 (0%) | ||||
| Resp, thoracic and mediastinal disorders - Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Sore throat | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 4/51 (7.8%) | ||||
| Voice alteration | 0/5 (0%) | 2/6 (33.3%) | 0/54 (0%) | 5/51 (9.8%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/5 (0%) | 1/6 (16.7%) | 12/54 (22.2%) | 10/51 (19.6%) | ||||
| Dry skin | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 5/51 (9.8%) | ||||
| Hyperhidrosis | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Nail discoloration | 0/5 (0%) | 0/6 (0%) | 0/54 (0%) | 1/51 (2%) | ||||
| Palmar-plantar erythrodysesthesia syndrome | 1/5 (20%) | 0/6 (0%) | 0/54 (0%) | 0/51 (0%) | ||||
| Pruritus | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 2/51 (3.9%) | ||||
| Rash acneiform | 1/5 (20%) | 1/6 (16.7%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Rash maculo-papular | 0/5 (0%) | 0/6 (0%) | 7/54 (13%) | 5/51 (9.8%) | ||||
| Skin and subcutaneous tissue disorders - Other | 0/5 (0%) | 0/6 (0%) | 4/54 (7.4%) | 1/51 (2%) | ||||
| Skin hyperpigmentation | 0/5 (0%) | 0/6 (0%) | 2/54 (3.7%) | 1/51 (2%) | ||||
| Skin ulceration | 0/5 (0%) | 1/6 (16.7%) | 0/54 (0%) | 0/51 (0%) | ||||
| Urticaria | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Vascular disorders | ||||||||
| Flushing | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 1/51 (2%) | ||||
| Hematoma | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
| Hot flashes | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 5/51 (9.8%) | ||||
| Hypertension | 1/5 (20%) | 0/6 (0%) | 9/54 (16.7%) | 8/51 (15.7%) | ||||
| Hypotension | 0/5 (0%) | 1/6 (16.7%) | 5/54 (9.3%) | 2/51 (3.9%) | ||||
| Thromboembolic event | 0/5 (0%) | 0/6 (0%) | 3/54 (5.6%) | 1/51 (2%) | ||||
| Vascular disorders-Other | 0/5 (0%) | 0/6 (0%) | 1/54 (1.9%) | 0/51 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | SWOG Statistician |
|---|---|
| Organization | SWOG Statistical Center |
| Phone | 2066674623 |
| mduong@fredhutch.org |
Responsible Party:
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01959139
Other Study ID Numbers:
- S1313
- NCI-2013-01776
- U10CA180888
- S1313
First Posted:
Oct 9, 2013
Last Update Posted:
Dec 1, 2021
Last Verified:
Nov 1, 2021