S0727 Gemcitabine Hydrochloride and Erlotinib Hydrochloride With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery
Study Details
Study Description
Brief Summary
This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine hydrochloride and erlotinib hydrochloride and to see how well they work compared with giving gemcitabine hydrochloride and erlotinib hydrochloride alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving erlotinib hydrochloride and gemcitabine hydrochloride together with monoclonal antibody therapy may kill more tumor cells.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To assess the appropriate dose of IMC-A12 (cixutumumab) to use in combination with gemcitabine (gemcitabine hydrochloride) and erlotinib (erlotinib hydrochloride). (Phase I)
- To assess progression-free survival in patients with metastatic pancreatic cancer treated with IMC-A12 plus gemcitabine and erlotinib compared to those treated with gemcitabine plus erlotinib alone. (Phase II) III. To assess overall survival in each of the two treatment arms in this group of patients. (Phase II) IV. To assess the total response probability (confirmed and unconfirmed, complete and partial responses) in each of the two treatment arms in the subset of this group of patients with measurable disease. (Phase II) V. To assess the qualitative and quantitative toxicities in each of the two treatment arms in this group of patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of cixutumumab followed by a randomized, phase II study.
Patients are initially enrolled into the phase I portion of the study to determine the recommended phase II dose (RPTD) of cixutumumab. Once the RPTD is determined, patients are enrolled into the phase II portion of the study.
PHASE I (LIMITED INSTITUTIONS): Patients receive erlotinib hydrochloride orally (PO) once daily on days 1-28, gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE II (ALL SWOG MEMBERS): Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive erlotinib hydrochloride, gemcitabine hydrochloride, and cixutumumab at the RPTD as in phase I.
ARM II: Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Previously collected tumor tissue is obtained for gene expression analyses by RT-PCR, RNA isolation, and cDNA synthesis. Blood samples are collected periodically for correlative studies. Samples are assessed for the potential relationship between gene expression levels, germline polymorphisms, Ras and P13K mutations and progression-free survival and overall survival.
After completion of study treatment, patients are followed every 6 months for up to 3 years.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm I (erlotinib, gemcitabine, cixutumumab) Patients receive erlotinib hydrochloride PO once daily on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
Biological: cixutumumab
Given IV
Other Names:
Drug: erlotinib hydrochloride
Given PO
Other Names:
Drug: gemcitabine hydrochloride
Given IV
Other Names:
|
Active Comparator: Arm II (erlotinib, gemcitabine) Patients receive erlotinib hydrochloride and gemcitabine hydrochloride as in arm I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: erlotinib hydrochloride
Given PO
Other Names:
Drug: gemcitabine hydrochloride
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose Determination [28 days]
Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite).
- Progression-Free Survival [Up to 3 years]
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
Secondary Outcome Measures
- Overall Survival [Up to 3 years]
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
- Response [Up to 3 years]
Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
- Toxicity [Up to 3 years]
Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically confirmed pancreatic adenocarcinoma
-
Stage IV disease (any T, any N, M1 [distant metastases])
-
Unresectable disease
-
Histologic diagnosis based on a metastatic site must be compatible with pancreatic cancer
-
Measurable and/or nonmeasurable disease
-
No endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer
-
No macroscopic residual disease post-resection as the only site of disease
-
No clinically significant ascites
-
No known brain metastases
-
Patients with neurologic signs or symptoms must undergo brain imaging studies AND studies must be negative for disease
-
Zubrod performance status 0-1
-
ANC ≥ 1,500/mcL
-
Platelet count ≥ 100,000/mcL
-
Hemoglobin ≥ 9 g/dL
-
Leukocytes ≥ 3,000/mcL
-
Total bilirubin normal
-
SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)
-
Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
-
Fasting serum glucose < 120 mg/dL or below the ULN
-
Patients with diabetes mellitus who meet this criterion must be on a stable dietary or therapeutic regimen for this condition
-
INR ≤ 1.5 and PTT ≤ 5 seconds above ULN
-
Not pregnant or nursing
-
Fertile patients must use effective contraception
-
Willing to submit previously collected tumor tissue specimens
-
No history of allergic reaction attributed to compounds of similar chemical or biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
-
No active acute or chronic infections requiring antibiotics
-
No significant ongoing cardiac problems, including any of the following:
-
Myocardial infarction within the past 6 months
-
Uncontrolled hypertension
-
Unstable angina
-
Uncontrolled arrhythmia
-
Congestive heart failure
-
No known HIV infection
-
No other prior malignancy, except for the following:
-
Adequately treated basal cell or squamous cell skin cancer
-
Carcinoma in situ of the cervix
-
Adequately treated stage I or II cancer from which the patient is currently in complete remission
-
Any other cancer from which the patient has been disease-free for 5 years
-
At least 14 days since prior surgery
-
At least 28 days since prior radiotherapy for palliation to metastatic sites
-
Patient must have other untreated metastatic sites that would qualify them for this protocol
-
At least 6 months since prior adjuvant chemotherapy
-
No prior chemotherapy, hormonal therapy, immunotherapy, or chemoradiotherapy for advanced or locally advanced pancreatic cancer, including drugs that target either EGFR or IGFR
-
No plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer
-
No prior gemcitabine hydrochloride
-
No prior chimerized or murine monoclonal antibody therapy
-
No concurrent CYP3A4 inducers including, but not limited to, any of the following:
-
Rifampicin
-
Rifabutin
-
Rifapentine
-
Phenytoin
-
Carbamazepine
-
Phenobarbital
-
Hypericum perforatum (St. John's wort)
-
No concurrent CYP3A4 inhibitors including, but not limited to, any of the following:
-
Atazanavir
-
Clarithromycin
-
Indinavir
-
Itraconazole
-
Ketoconazole
-
Nefazodone
-
Nelfinavir
-
Ritonavir
-
Saquinavir
-
Telithromycin
-
Troleandomycin
-
Voriconazole
-
Concurrent prophylactic low-dose coumadin or low molecular weight heparin allowed provided coagulation criteria are met
-
Full-dose anticoagulation allowed provided coagulation criteria are met and are under strict control and monitoring
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | NEA Baptist Memorial Hospital | Jonesboro | Arkansas | United States | 72401 |
2 | Alta Bates Summit Medical Center-Herrick Campus | Berkeley | California | United States | 94704 |
3 | Mills - Peninsula Hospitals | Burlingame | California | United States | 94010 |
4 | East Bay Radiation Oncology Center | Castro Valley | California | United States | 94546 |
5 | Eden Hospital Medical Center | Castro Valley | California | United States | 94546 |
6 | Valley Medical Oncology Consultants-Castro Valley | Castro Valley | California | United States | 94546 |
7 | City of Hope Medical Center | Duarte | California | United States | 91010 |
8 | Valley Medical Oncology Consultants-Fremont | Fremont | California | United States | 94538 |
9 | Glendale Memorial Hospital and Health Center | Glendale | California | United States | 91204 |
10 | Marin General Hospital | Greenbrae | California | United States | 94904 |
11 | Sutter Health Western Division Cancer Research Group | Greenbrae | California | United States | 94904 |
12 | University of Southern California | Los Angeles | California | United States | 90033-0804 |
13 | Contra Costa Regional Medical Center | Martinez | California | United States | 94553-3156 |
14 | El Camino Hospital | Mountain View | California | United States | 94040 |
15 | Highland General Hospital | Oakland | California | United States | 94602 |
16 | Alta Bates Summit Medical Center - Summit Campus | Oakland | California | United States | 94609 |
17 | Bay Area Breast Surgeons Inc | Oakland | California | United States | 94609 |
18 | Bay Area Tumor Institute | Oakland | California | United States | 94609 |
19 | Larry G Strieff MD Medical Corporation | Oakland | California | United States | 94609 |
20 | Tom K Lee Inc | Oakland | California | United States | 94609 |
21 | University of California Medical Center At Irvine-Orange Campus | Orange | California | United States | 92868 |
22 | Valley Care Health System - Pleasanton | Pleasanton | California | United States | 94588 |
23 | Valley Medical Oncology Consultants | Pleasanton | California | United States | 94588 |
24 | California Pacific Medical Center | San Francisco | California | United States | 94118 |
25 | Doctors Medical Center- JC Robinson Regional Cancer Center | San Pablo | California | United States | 94806 |
26 | Sutter Solano Medical Center | Vallejo | California | United States | 94589 |
27 | Poudre Valley Hospital | Fort Collins | Colorado | United States | 80524 |
28 | Piedmont Hospital | Atlanta | Georgia | United States | 30309 |
29 | Atlanta Regional CCOP | Atlanta | Georgia | United States | 30342 |
30 | Northside Hospital | Atlanta | Georgia | United States | 30342 |
31 | Saint Joseph's Hospital of Atlanta | Atlanta | Georgia | United States | 30342 |
32 | Well Star Cobb Hospital | Austell | Georgia | United States | 30106 |
33 | John B Amos Cancer Center | Columbus | Georgia | United States | 31904 |
34 | Dekalb Medical Center | Decatur | Georgia | United States | 30033 |
35 | Gwinnett Medical Center | Lawrenceville | Georgia | United States | 30045 |
36 | Wellstar Kennestone Hospital | Marietta | Georgia | United States | 30060 |
37 | Southern Regional Medical Center | Riverdale | Georgia | United States | 30274 |
38 | Harbin Clinic Medical Oncology and Clinical Research | Rome | Georgia | United States | 30165 |
39 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31403 |
40 | Saint Joseph's-Candler Health System | Savannah | Georgia | United States | 31405 |
41 | South Georgia Medical Center | Valdosta | Georgia | United States | 31603 |
42 | Cancer Care Center of Decatur | Decatur | Illinois | United States | 62526 |
43 | Decatur Memorial Hospital | Decatur | Illinois | United States | 62526 |
44 | Crossroads Cancer Center | Effingham | Illinois | United States | 62401 |
45 | Menorah Medical Center | Overland Park | Kansas | United States | 66209 |
46 | Saint Luke's South Hospital | Overland Park | Kansas | United States | 66213 |
47 | Shawnee Mission Medical Center | Shawnee Mission | Kansas | United States | 66204 |
48 | Christus Saint Frances Cabrini Hospital | Alexandria | Louisiana | United States | 71301 |
49 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
50 | Boston Medical Center | Boston | Massachusetts | United States | 02118 |
51 | Bronson Battle Creek | Battle Creek | Michigan | United States | 49017 |
52 | Mecosta County Medical Center | Big Rapids | Michigan | United States | 49307 |
53 | Wayne State University | Detroit | Michigan | United States | 48202 |
54 | Grand Rapids Clinical Oncology Program | Grand Rapids | Michigan | United States | 49503 |
55 | Saint Mary's Health Care | Grand Rapids | Michigan | United States | 49503 |
56 | Spectrum Health at Butterworth Campus | Grand Rapids | Michigan | United States | 49503 |
57 | Mercy Health Partners-Mercy Campus | Muskegon | Michigan | United States | 49444 |
58 | William Beaumont Hospital | Royal Oak | Michigan | United States | 48073 |
59 | Munson Medical Center | Traverse City | Michigan | United States | 49684 |
60 | Metro Health Hospital | Wyoming | Michigan | United States | 49519 |
61 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
62 | Truman Medical Center | Kansas City | Missouri | United States | 64108 |
63 | Saint Luke's Cancer Institute | Kansas City | Missouri | United States | 64111 |
64 | Saint Luke's Hospital of Kansas City | Kansas City | Missouri | United States | 64111 |
65 | Saint Joseph Health Center | Kansas City | Missouri | United States | 64114 |
66 | North Kansas City Hospital | Kansas City | Missouri | United States | 64116 |
67 | Heartland Hematology and Oncology Associates Incorporated | Kansas City | Missouri | United States | 64118 |
68 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
69 | Saint Luke's East - Lee's Summit | Lee's Summit | Missouri | United States | 64086 |
70 | Liberty Hospital | Liberty | Missouri | United States | 64068 |
71 | Liberty Radiation Oncology Clinic | Liberty | Missouri | United States | 64068 |
72 | Heartland Regional Medical Center | Saint Joseph | Missouri | United States | 64506 |
73 | Saint Joseph Oncology Inc | Saint Joseph | Missouri | United States | 64507 |
74 | Saint Louis University Hospital | Saint Louis | Missouri | United States | 63110 |
75 | Montana Cancer Consortium CCOP | Billings | Montana | United States | 59101 |
76 | Northern Rockies Radiation Oncology Center | Billings | Montana | United States | 59101 |
77 | Saint Vincent Healthcare | Billings | Montana | United States | 59101 |
78 | Hematology-Oncology Centers of the Northern Rockies PC | Billings | Montana | United States | 59102 |
79 | Billings Clinic | Billings | Montana | United States | 59107-7000 |
80 | Bozeman Deaconess Cancer Center | Bozeman | Montana | United States | 59715 |
81 | Bozeman Deaconess Hospital | Bozeman | Montana | United States | 59715 |
82 | Saint James Community Hospital and Cancer Treatment Center | Butte | Montana | United States | 59701 |
83 | Benefis Healthcare- Sletten Cancer Institute | Great Falls | Montana | United States | 59405 |
84 | Berdeaux, Donald MD (UIA Investigator) | Great Falls | Montana | United States | 59405 |
85 | Great Falls Clinic | Great Falls | Montana | United States | 59405 |
86 | Northern Montana Hospital | Havre | Montana | United States | 59501 |
87 | Saint Peter's Community Hospital | Helena | Montana | United States | 59601 |
88 | Glacier Oncology PLLC | Kalispell | Montana | United States | 59901 |
89 | Kalispell Medical Oncology | Kalispell | Montana | United States | 59901 |
90 | Kalispell Regional Medical Center | Kalispell | Montana | United States | 59901 |
91 | Community Medical Hospital | Missoula | Montana | United States | 59801 |
92 | Montana Cancer Specialists | Missoula | Montana | United States | 59802 |
93 | Saint Patrick Hospital - Community Hospital | Missoula | Montana | United States | 59802 |
94 | Guardian Oncology and Center for Wellness | Missoula | Montana | United States | 59804 |
95 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87106 |
96 | Arnot Ogden Medical Center | Elmira | New York | United States | 14905 |
97 | Highland Hospital | Rochester | New York | United States | 14620 |
98 | Interlakes Foundation Inc-Rochester | Rochester | New York | United States | 14623 |
99 | University of Rochester | Rochester | New York | United States | 14642 |
100 | Randolph Hospital | Asheboro | North Carolina | United States | 27203 |
101 | Carolinas Medical Center | Charlotte | North Carolina | United States | 28203 |
102 | Presbyterian Hospital | Charlotte | North Carolina | United States | 28204 |
103 | Wayne Memorial Hospital | Goldsboro | North Carolina | United States | 27534 |
104 | Cone Health Cancer Center | Greensboro | North Carolina | United States | 27403 |
105 | Margaret R Pardee Memorial Hospital | Hendersonville | North Carolina | United States | 28791 |
106 | Annie Penn Memorial Hospital | Reidsville | North Carolina | United States | 27320 |
107 | Akron General Medical Center | Akron | Ohio | United States | 44307 |
108 | Veterans Administration Medical Center - Cincinnati | Cincinnati | Ohio | United States | 45220 |
109 | University of Cincinnati | Cincinnati | Ohio | United States | 45267 |
110 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
111 | The Don and Sybil Harrington Cancer Center | Amarillo | Texas | United States | 79106 |
112 | University of Texas Medical Branch at Galveston | Galveston | Texas | United States | 77555-0565 |
113 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
114 | Ben Taub General Hospital | Houston | Texas | United States | 77030 |
115 | Methodist Hospital | Houston | Texas | United States | 77030 |
116 | Saint Luke's Episcopal Hospital | Houston | Texas | United States | 77030 |
117 | Veterans Administration Medical Center | Houston | Texas | United States | 77030 |
118 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
119 | American Fork Hospital | American Fork | Utah | United States | 84003 |
120 | Sandra L Maxwell Cancer Center | Cedar City | Utah | United States | 84720 |
121 | Logan Regional Hospital | Logan | Utah | United States | 84321 |
122 | Intermountain Medical Center | Murray | Utah | United States | 84157 |
123 | McKay-Dee Hospital Center | Ogden | Utah | United States | 84403 |
124 | Utah Valley Regional Medical Center | Provo | Utah | United States | 84604-3337 |
125 | Dixie Medical Center Regional Cancer Center | Saint George | Utah | United States | 84770 |
126 | Intermountain Health Care | Salt Lake City | Utah | United States | 84103 |
127 | Utah Cancer Specialists-Salt Lake City | Salt Lake City | Utah | United States | 84106 |
128 | LDS Hospital | Salt Lake City | Utah | United States | 84143 |
129 | Memorial Hospital Of Martinsville | Martinsville | Virginia | United States | 24115 |
130 | PeaceHealth Saint Joseph Medical Center | Bellingham | Washington | United States | 98225 |
131 | Harrison Bremerton Hematology and Oncology | Bremerton | Washington | United States | 98310 |
132 | Columbia Basin Hematology and Oncology PLLC | Kennewick | Washington | United States | 99336 |
133 | Skagit Valley Hospital | Mount Vernon | Washington | United States | 98274 |
134 | Harrison Poulsbo Hematology and Oncology | Poulsbo | Washington | United States | 98370 |
135 | Harborview Medical Center | Seattle | Washington | United States | 98104 |
136 | Minor and James Medical PLLC | Seattle | Washington | United States | 98104 |
137 | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
138 | Group Health Cooperative | Seattle | Washington | United States | 98112 |
139 | Swedish Medical Center-First Hill | Seattle | Washington | United States | 98122-4307 |
140 | The Polyclinic | Seattle | Washington | United States | 98122 |
141 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
142 | Cancer Care Northwest - Spokane South | Spokane | Washington | United States | 99202 |
143 | Evergreen Hematology and Oncology PS | Spokane | Washington | United States | 99218 |
144 | Wenatchee Valley Medical Center | Wenatchee | Washington | United States | 98801 |
145 | Rocky Mountain Oncology | Casper | Wyoming | United States | 82609 |
146 | Welch Cancer Center | Sheridan | Wyoming | United States | 82801 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Philip Philip, Southwest Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00797
- NCI-2009-00797
- CDR0000586427
- SWOG-S0727
- S0727
- S0727
- U10CA032102
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine |
---|---|---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. |
Period Title: Overall Study | |||
STARTED | 10 | 60 | 64 |
Eligible and Began Protocol Therapy | 9 | 57 | 59 |
COMPLETED | 0 | 0 | 0 |
NOT COMPLETED | 10 | 60 | 64 |
Baseline Characteristics
Arm/Group Title | Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine | Total |
---|---|---|---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. | Total of all reporting groups |
Overall Participants | 9 | 57 | 59 | 125 |
Age (years) [Median (Full Range) ] | ||||
Median (Full Range) [years] |
61
|
63
|
64
|
63
|
Sex: Female, Male (Count of Participants) | ||||
Female |
3
33.3%
|
34
59.6%
|
25
42.4%
|
62
49.6%
|
Male |
6
66.7%
|
23
40.4%
|
34
57.6%
|
63
50.4%
|
Race/Ethnicity, Customized (participants) [Number] | ||||
White |
5
55.6%
|
44
77.2%
|
51
86.4%
|
100
80%
|
Black |
2
22.2%
|
10
17.5%
|
6
10.2%
|
18
14.4%
|
Asian |
1
11.1%
|
2
3.5%
|
2
3.4%
|
5
4%
|
Unknown |
1
11.1%
|
1
1.8%
|
0
0%
|
2
1.6%
|
Race/Ethnicity, Customized (participants) [Number] | ||||
Hispanic |
1
11.1%
|
3
5.3%
|
5
8.5%
|
9
7.2%
|
Non-Hispanic |
8
88.9%
|
53
93%
|
47
79.7%
|
108
86.4%
|
Unknown |
0
0%
|
1
1.8%
|
7
11.9%
|
8
6.4%
|
Outcome Measures
Title | Overall Survival |
---|---|
Description | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
Time Frame | Up to 3 years |
Outcome Measure Data
Analysis Population Description |
---|
Eligible patients in the Phase II portion of the study. |
Arm/Group Title | Erlotinib + Gemcitabine + IMC-A12 | Erlotinib + Gemcitabine |
---|---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. |
Measure Participants | 57 | 59 |
Median (95% Confidence Interval) [months] |
7.0
|
6.5
|
Title | Maximum Tolerated Dose Determination |
---|---|
Description | Maximum dose of IMC-A12 (in combination with erlotinib and gemcitabine) at which 3/10 or fewer patients have dose-limiting toxicities (DLT). Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0). DLT apply only during cycle 1 and should be drug-related (possible, probable, or definite). |
Time Frame | 28 days |
Outcome Measure Data
Analysis Population Description |
---|
Phase I patients receiving at least three doses of the assigned dose during Cycle 1 or whom developed a DLT. |
Arm/Group Title | Ph I: Erlotinib + Gemcitabine + IMC-A12 |
---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. |
Measure Participants | 10 |
Number [mg/kg IMC-A12] |
6
|
Title | Response |
---|---|
Description | Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. |
Time Frame | Up to 3 years |
Outcome Measure Data
Analysis Population Description |
---|
Eligible patients in the Phase II portion of the study with measurable disease and adequate response assessment. |
Arm/Group Title | Erlotinib + Gemcitabine + IMC-A12 | Erlotinib + Gemcitabine |
---|---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. |
Measure Participants | 51 | 53 |
Number (95% Confidence Interval) [percentage of participants] |
13.7
152.2%
|
15.3
26.8%
|
Title | Toxicity |
---|---|
Description | Number of patients with Grade 3 through 5 adverse events that are related to study drug. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Time Frame | Up to 3 years |
Outcome Measure Data
Analysis Population Description |
---|
Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included. |
Arm/Group Title | Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine |
---|---|---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. |
Measure Participants | 9 | 57 | 57 |
ALT, SGPT (serum glutamic pyruvic transaminase) |
0
0%
|
9
15.8%
|
4
6.8%
|
AST, SGOT |
0
0%
|
6
10.5%
|
3
5.1%
|
Acidosis (metabolic or respiratory) |
0
0%
|
1
1.8%
|
0
0%
|
Adult respiratory distress syndrome (ARDS) |
0
0%
|
0
0%
|
1
1.7%
|
Albumin, serum-low (hypoalbuminemia) |
0
0%
|
3
5.3%
|
0
0%
|
Alkaline phosphatase |
0
0%
|
4
7%
|
3
5.1%
|
Allergic reaction/hypersensitivity |
1
11.1%
|
0
0%
|
0
0%
|
Anorexia |
1
11.1%
|
7
12.3%
|
6
10.2%
|
Bilirubin (hyperbilirubinemia) |
0
0%
|
5
8.8%
|
0
0%
|
Calcium, serum-low (hypocalcemia) |
0
0%
|
1
1.8%
|
1
1.7%
|
Cardiac troponin I (cTnI) |
0
0%
|
3
5.3%
|
0
0%
|
Cardiac-ischemia/infarction |
0
0%
|
0
0%
|
1
1.7%
|
Cardiopulmonary arrest, cause unknown (non-fatal) |
0
0%
|
0
0%
|
1
1.7%
|
Dehydration |
3
33.3%
|
6
10.5%
|
5
8.5%
|
Diarrhea |
2
22.2%
|
3
5.3%
|
2
3.4%
|
Dizziness |
0
0%
|
1
1.8%
|
0
0%
|
Dysphagia (difficulty swallowing) |
0
0%
|
0
0%
|
1
1.7%
|
Dyspnea (shortness of breath) |
0
0%
|
2
3.5%
|
4
6.8%
|
Edema: limb |
0
0%
|
0
0%
|
1
1.7%
|
Edema: trunk/genital |
0
0%
|
0
0%
|
1
1.7%
|
Fatigue (asthenia, lethargy, malaise) |
4
44.4%
|
16
28.1%
|
12
20.3%
|
GGT (gamma-glutamyl transpeptidase) |
0
0%
|
1
1.8%
|
0
0%
|
Glucose, serum-high (hyperglycemia) |
2
22.2%
|
16
28.1%
|
1
1.7%
|
Hemoglobin |
0
0%
|
9
15.8%
|
8
13.6%
|
Hypotension |
0
0%
|
3
5.3%
|
1
1.7%
|
Hypoxia |
0
0%
|
1
1.8%
|
2
3.4%
|
Inf (clin/microbio) w/Gr 3-4 neuts - Blood |
0
0%
|
0
0%
|
1
1.7%
|
Inf (clin/microbio) w/Gr 3-4 neuts - UTI |
0
0%
|
0
0%
|
1
1.7%
|
Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree |
0
0%
|
1
1.8%
|
0
0%
|
Inf w/normal ANC or Gr 1-2 neutrophils - Blood |
1
11.1%
|
0
0%
|
1
1.7%
|
Inf w/normal ANC or Gr 1-2 neutrophils - Lung |
0
0%
|
1
1.8%
|
2
3.4%
|
Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas |
0
0%
|
0
0%
|
1
1.7%
|
Inf w/normal ANC or Gr 1-2 neutrophils - Skin |
0
0%
|
1
1.8%
|
0
0%
|
Inf w/normal ANC or Gr 1-2 neutrophils - UTI |
0
0%
|
0
0%
|
1
1.7%
|
Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig |
0
0%
|
1
1.8%
|
0
0%
|
Infection-Other (Specify) |
0
0%
|
1
1.8%
|
0
0%
|
Left ventricular systolic dysfunction |
0
0%
|
1
1.8%
|
0
0%
|
Leukocytes (total WBC) |
1
11.1%
|
9
15.8%
|
5
8.5%
|
Liver dysfunction/failure (clinical) |
0
0%
|
0
0%
|
1
1.7%
|
Lymphatics-Other (Specify) |
0
0%
|
0
0%
|
1
1.7%
|
Lymphopenia |
1
11.1%
|
4
7%
|
5
8.5%
|
Magnesium, serum-low (hypomagnesemia) |
0
0%
|
1
1.8%
|
0
0%
|
Mucositis/stomatitis (functional/symp) - Oral cav |
0
0%
|
1
1.8%
|
0
0%
|
Muscle weakness, not d/t neuropathy - Extrem-lower |
0
0%
|
1
1.8%
|
0
0%
|
Muscle weakness, not d/t neuropathy - body/general |
0
0%
|
5
8.8%
|
3
5.1%
|
Nausea |
4
44.4%
|
9
15.8%
|
6
10.2%
|
Neuropathy: sensory |
0
0%
|
1
1.8%
|
0
0%
|
Neutrophils/granulocytes (ANC/AGC) |
3
33.3%
|
21
36.8%
|
10
16.9%
|
Obstruction, GI - Duodenum |
0
0%
|
0
0%
|
1
1.7%
|
Opportunistic inf associated w/gt=Gr 2 lymphopenia |
1
11.1%
|
0
0%
|
0
0%
|
PTT (Partial thromboplastin time) |
0
0%
|
1
1.8%
|
0
0%
|
Pain - Abdomen NOS |
0
0%
|
0
0%
|
1
1.7%
|
Pain - Eye |
0
0%
|
1
1.8%
|
0
0%
|
Pain - Head/headache |
0
0%
|
1
1.8%
|
0
0%
|
Pain - Muscle |
0
0%
|
0
0%
|
1
1.7%
|
Pancreas, exocrine enzyme deficiency |
0
0%
|
1
1.8%
|
0
0%
|
Pancreatic endocrine: glucose intolerance |
0
0%
|
6
10.5%
|
0
0%
|
Pericardial effusion (non-malignant) |
0
0%
|
0
0%
|
1
1.7%
|
Personality/behavioral |
0
0%
|
1
1.8%
|
0
0%
|
Platelets |
2
22.2%
|
16
28.1%
|
7
11.9%
|
Pleural effusion (non-malignant) |
0
0%
|
0
0%
|
1
1.7%
|
Pneumonitis/pulmonary infiltrates |
0
0%
|
1
1.8%
|
2
3.4%
|
Potassium, serum-low (hypokalemia) |
0
0%
|
1
1.8%
|
1
1.7%
|
Pulmonary/Upper Respiratory-Other (Specify) |
0
0%
|
1
1.8%
|
1
1.7%
|
Rash/desquamation |
0
0%
|
0
0%
|
1
1.7%
|
Rash: acne/acneiform |
0
0%
|
3
5.3%
|
2
3.4%
|
Rash: erythema multiforme |
0
0%
|
1
1.8%
|
0
0%
|
SVT and nodal arrhythmia - Atrial fibrillation |
0
0%
|
1
1.8%
|
0
0%
|
Sodium, serum-low (hyponatremia) |
1
11.1%
|
5
8.8%
|
1
1.7%
|
Stricture/stenosis (incl anastomotic), Stomach |
0
0%
|
0
0%
|
1
1.7%
|
Syncope (fainting) |
0
0%
|
3
5.3%
|
0
0%
|
Thrombosis/embolism (vascular access-related) |
0
0%
|
1
1.8%
|
0
0%
|
Thrombosis/thrombus/embolism |
0
0%
|
4
7%
|
1
1.7%
|
Tremor |
0
0%
|
1
1.8%
|
0
0%
|
Uric acid, serum-high (hyperuricemia) |
0
0%
|
1
1.8%
|
0
0%
|
Ventricular arrhythmia - Ventricular fibrillation |
0
0%
|
1
1.8%
|
0
0%
|
Vision-blurred vision |
0
0%
|
1
1.8%
|
0
0%
|
Vision-photophobia |
0
0%
|
1
1.8%
|
0
0%
|
Vomiting |
2
22.2%
|
5
8.8%
|
1
1.7%
|
Weight loss |
0
0%
|
2
3.5%
|
0
0%
|
Title | Progression-Free Survival |
---|---|
Description | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. |
Time Frame | Up to 3 years |
Outcome Measure Data
Analysis Population Description |
---|
Eligible patients in the Phase II portion of the study. |
Arm/Group Title | Erlotinib + Gemcitabine + IMC-A12 | Erlotinib + Gemcitabine |
---|---|---|
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. |
Measure Participants | 57 | 59 |
Median (95% Confidence Interval) [months] |
3.6
|
3.6
|
Adverse Events
Time Frame | Up to 3 years | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine | |||
Arm/Group Description | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15, and IMC-A12 6 mg/kg IV days 1, 8, 15 and 22. One cycle = 28 days. | Erlotinib 100 mg PO once daily, Gemcitabine 1,000 mg/m^2 IV days 1, 8 and 15. One cycle = 28 days. | |||
All Cause Mortality |
||||||
Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/9 (55.6%) | 34/57 (59.6%) | 33/57 (57.9%) | |||
Blood and lymphatic system disorders | ||||||
Hemoglobin | 0/9 (0%) | 6/57 (10.5%) | 2/57 (3.5%) | |||
Lymphatics-Other (Specify) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Cardiac disorders | ||||||
Atrioventricular block - first degree | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Cardiac-ischemia/infarction | 0/9 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | |||
Left ventricular systolic dysfunction | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Pericardial effusion (non-malignant) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
SVT and nodal arrhythmia - Atrial fibrillation | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Ventricular arrhythmia - Ventricular fibrillation | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Gastrointestinal disorders | ||||||
Ascites (non-malignant) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Constipation | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Diarrhea | 1/9 (11.1%) | 1/57 (1.8%) | 0/57 (0%) | |||
Distention/bloating, abdominal | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Gastrointestinal-Other (Specify) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Hemorrhage, GI - Duodenum | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Hemorrhage, GI - Rectum | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Hemorrhage, GI - Upper GI NOS | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Ileus, GI (functional obstruction of bowel) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Incontinence, anal | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Nausea | 3/9 (33.3%) | 3/57 (5.3%) | 3/57 (5.3%) | |||
Obstruction, GI - Duodenum | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Obstruction, GI - Small bowel NOS | 1/9 (11.1%) | 0/57 (0%) | 1/57 (1.8%) | |||
Obstruction, GI - Stomach | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Pain - Abdomen NOS | 0/9 (0%) | 9/57 (15.8%) | 3/57 (5.3%) | |||
Vomiting | 2/9 (22.2%) | 4/57 (7%) | 3/57 (5.3%) | |||
General disorders | ||||||
Death not associated with CTCAE term - Death NOS | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Edema: limb | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Fatigue (asthenia, lethargy, malaise) | 1/9 (11.1%) | 3/57 (5.3%) | 4/57 (7%) | |||
Hepatobiliary disorders | ||||||
Hepatobiliary/Pancreas-Other (Specify) | 0/9 (0%) | 2/57 (3.5%) | 0/57 (0%) | |||
Liver dysfunction/failure (clinical) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Portal vein flow | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Stricture/stenosis (incl anastomotic)-Biliary tree | 0/9 (0%) | 0/57 (0%) | 2/57 (3.5%) | |||
Immune system disorders | ||||||
Allergic reaction/hypersensitivity | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Infections and infestations | ||||||
Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 1/9 (11.1%) | 0/57 (0%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 0/9 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Pancreas | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Perit cav | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 0/9 (0%) | 2/57 (3.5%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils -Up aerodig | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils-Foreign bod | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Infection with unknown ANC - Blood | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Injury, poisoning and procedural complications | ||||||
Fracture | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Thrombosis/embolism (vascular access-related) | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Investigations | ||||||
ALT, SGPT (serum glutamic pyruvic transaminase) | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
AST, SGOT | 0/9 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | |||
Alkaline phosphatase | 0/9 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | |||
Amylase | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Bilirubin (hyperbilirubinemia) | 0/9 (0%) | 5/57 (8.8%) | 2/57 (3.5%) | |||
Cardiac troponin I (cTnI) | 0/9 (0%) | 2/57 (3.5%) | 1/57 (1.8%) | |||
Creatinine | 1/9 (11.1%) | 1/57 (1.8%) | 0/57 (0%) | |||
Lipase | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Lymphopenia | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Pancreas, exocrine enzyme deficiency | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Platelets | 0/9 (0%) | 2/57 (3.5%) | 0/57 (0%) | |||
Weight loss | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Metabolism and nutrition disorders | ||||||
Acidosis (metabolic or respiratory) | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Albumin, serum-low (hypoalbuminemia) | 0/9 (0%) | 3/57 (5.3%) | 0/57 (0%) | |||
Anorexia | 0/9 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | |||
Calcium, serum-low (hypocalcemia) | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Dehydration | 4/9 (44.4%) | 6/57 (10.5%) | 5/57 (8.8%) | |||
Glucose, serum-high (hyperglycemia) | 0/9 (0%) | 4/57 (7%) | 1/57 (1.8%) | |||
Potassium, serum-low (hypokalemia) | 0/9 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | |||
Sodium, serum-low (hyponatremia) | 0/9 (0%) | 3/57 (5.3%) | 0/57 (0%) | |||
Uric acid, serum-high (hyperuricemia) | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Arthritis (non-septic) | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Muscle weakness, not d/t neuropathy - body/general | 0/9 (0%) | 5/57 (8.8%) | 1/57 (1.8%) | |||
Pain - Back | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Pain - Muscle | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Death - Disease progression NOS | 1/9 (11.1%) | 9/57 (15.8%) | 10/57 (17.5%) | |||
Pain - Tumor pain | 0/9 (0%) | 3/57 (5.3%) | 1/57 (1.8%) | |||
Nervous system disorders | ||||||
CNS cerebrovascular ischemia | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Dizziness | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Neuropathy: motor | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Syncope (fainting) | 0/9 (0%) | 2/57 (3.5%) | 0/57 (0%) | |||
Psychiatric disorders | ||||||
Confusion | 1/9 (11.1%) | 2/57 (3.5%) | 0/57 (0%) | |||
Mood alteration - agitation | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Personality/behavioral | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Psychosis (hallucinations/delusions) | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Renal and urinary disorders | ||||||
Incontinence, urinary | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Adult respiratory distress syndrome (ARDS) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Dyspnea (shortness of breath) | 0/9 (0%) | 2/57 (3.5%) | 5/57 (8.8%) | |||
Hypoxia | 0/9 (0%) | 1/57 (1.8%) | 3/57 (5.3%) | |||
Pleural effusion (non-malignant) | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Pneumonitis/pulmonary infiltrates | 0/9 (0%) | 1/57 (1.8%) | 3/57 (5.3%) | |||
Pulmonary/Upper Respiratory-Other (Specify) | 0/9 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | |||
Skin and subcutaneous tissue disorders | ||||||
Rash/desquamation | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Rash: acne/acneiform | 0/9 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Skin breakdown/decubitus ulcer | 0/9 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
Vascular disorders | ||||||
Hypotension | 0/9 (0%) | 2/57 (3.5%) | 3/57 (5.3%) | |||
Thrombosis/thrombus/embolism | 0/9 (0%) | 5/57 (8.8%) | 3/57 (5.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
Ph I: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine + IMC-A12 | Ph II: Erlotinib + Gemcitabine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/9 (100%) | 56/57 (98.2%) | 57/57 (100%) | |||
Blood and lymphatic system disorders | ||||||
Hemoglobin | 8/9 (88.9%) | 38/57 (66.7%) | 39/57 (68.4%) | |||
Cardiac disorders | ||||||
Cardiac Arrhythmia-Other (Specify) | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Cardiac-ischemia/infarction | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
SVT and nodal arrhythmia - Atrial tachycardia/PAT | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
SVT and nodal arrhythmia - Sinus bradycardia | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Ear and labyrinth disorders | ||||||
Auditory/Ear-Other (Specify) | 2/9 (22.2%) | 0/57 (0%) | 0/57 (0%) | |||
Eye disorders | ||||||
Dry eye syndrome | 1/9 (11.1%) | 4/57 (7%) | 0/57 (0%) | |||
Ocular/Visual-Other (Specify) | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Vision-blurred vision | 0/9 (0%) | 5/57 (8.8%) | 4/57 (7%) | |||
Vision-flashing lights/floaters | 3/9 (33.3%) | 3/57 (5.3%) | 0/57 (0%) | |||
Gastrointestinal disorders | ||||||
Constipation | 7/9 (77.8%) | 33/57 (57.9%) | 27/57 (47.4%) | |||
Diarrhea | 5/9 (55.6%) | 32/57 (56.1%) | 27/57 (47.4%) | |||
Distention/bloating, abdominal | 0/9 (0%) | 0/57 (0%) | 3/57 (5.3%) | |||
Dry mouth/salivary gland (xerostomia) | 1/9 (11.1%) | 6/57 (10.5%) | 5/57 (8.8%) | |||
Flatulence | 0/9 (0%) | 3/57 (5.3%) | 5/57 (8.8%) | |||
Gastrointestinal-Other (Specify) | 0/9 (0%) | 3/57 (5.3%) | 5/57 (8.8%) | |||
Heartburn/dyspepsia | 3/9 (33.3%) | 10/57 (17.5%) | 4/57 (7%) | |||
Hemorrhage, GI - Abdomen NOS | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Hemorrhoids | 1/9 (11.1%) | 4/57 (7%) | 0/57 (0%) | |||
Malabsorption | 0/9 (0%) | 0/57 (0%) | 3/57 (5.3%) | |||
Mucositis/stomatitis (clinical exam) - Oral cavity | 1/9 (11.1%) | 17/57 (29.8%) | 0/57 (0%) | |||
Mucositis/stomatitis (functional/symp) - Oral cav | 2/9 (22.2%) | 10/57 (17.5%) | 4/57 (7%) | |||
Nausea | 9/9 (100%) | 43/57 (75.4%) | 34/57 (59.6%) | |||
Obstruction, GI - Small bowel NOS | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Pain - Abdomen NOS | 5/9 (55.6%) | 17/57 (29.8%) | 21/57 (36.8%) | |||
Pain - Oral cavity | 0/9 (0%) | 4/57 (7%) | 0/57 (0%) | |||
Pain - Rectum | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Pain - Stomach | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Vomiting | 6/9 (66.7%) | 26/57 (45.6%) | 25/57 (43.9%) | |||
General disorders | ||||||
Edema: limb | 1/9 (11.1%) | 12/57 (21.1%) | 16/57 (28.1%) | |||
Fatigue (asthenia, lethargy, malaise) | 8/9 (88.9%) | 47/57 (82.5%) | 43/57 (75.4%) | |||
Fever in absence of neutropenia, ANC lt1.0x10e9/L | 3/9 (33.3%) | 5/57 (8.8%) | 15/57 (26.3%) | |||
Pain - Chest/thorax NOS | 0/9 (0%) | 3/57 (5.3%) | 0/57 (0%) | |||
Pain-Other (Specify) | 0/9 (0%) | 7/57 (12.3%) | 3/57 (5.3%) | |||
Rigors/chills | 1/9 (11.1%) | 5/57 (8.8%) | 7/57 (12.3%) | |||
Immune system disorders | ||||||
Allergic reaction/hypersensitivity | 0/9 (0%) | 0/57 (0%) | 3/57 (5.3%) | |||
Allergy/Immunology-Other (Specify) | 0/9 (0%) | 3/57 (5.3%) | 0/57 (0%) | |||
Infections and infestations | ||||||
Inf w/normal ANC or Gr 1-2 neutrophils - Ab NOS | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Skin | 2/9 (22.2%) | 3/57 (5.3%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - UTI | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Infection-Other (Specify) | 0/9 (0%) | 3/57 (5.3%) | 3/57 (5.3%) | |||
Opportunistic inf associated w/gt=Gr 2 lymphopenia | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Injury, poisoning and procedural complications | ||||||
Bruising (in absence of Gr 3-4 thrombocytopenia) | 2/9 (22.2%) | 0/57 (0%) | 0/57 (0%) | |||
Investigations | ||||||
ALT, SGPT (serum glutamic pyruvic transaminase) | 8/9 (88.9%) | 34/57 (59.6%) | 30/57 (52.6%) | |||
AST, SGOT | 8/9 (88.9%) | 36/57 (63.2%) | 31/57 (54.4%) | |||
Alkaline phosphatase | 5/9 (55.6%) | 35/57 (61.4%) | 25/57 (43.9%) | |||
Bilirubin (hyperbilirubinemia) | 3/9 (33.3%) | 18/57 (31.6%) | 18/57 (31.6%) | |||
Creatinine | 3/9 (33.3%) | 9/57 (15.8%) | 8/57 (14%) | |||
INR (of prothrombin time) | 0/9 (0%) | 4/57 (7%) | 7/57 (12.3%) | |||
Leukocytes (total WBC) | 4/9 (44.4%) | 29/57 (50.9%) | 29/57 (50.9%) | |||
Lymphopenia | 1/9 (11.1%) | 8/57 (14%) | 10/57 (17.5%) | |||
Metabolic/Laboratory-Other (Specify) | 0/9 (0%) | 5/57 (8.8%) | 4/57 (7%) | |||
Neutrophils/granulocytes (ANC/AGC) | 6/9 (66.7%) | 30/57 (52.6%) | 20/57 (35.1%) | |||
PTT (Partial thromboplastin time) | 0/9 (0%) | 3/57 (5.3%) | 4/57 (7%) | |||
Platelets | 9/9 (100%) | 42/57 (73.7%) | 36/57 (63.2%) | |||
Weight loss | 3/9 (33.3%) | 27/57 (47.4%) | 25/57 (43.9%) | |||
Metabolism and nutrition disorders | ||||||
Albumin, serum-low (hypoalbuminemia) | 2/9 (22.2%) | 25/57 (43.9%) | 18/57 (31.6%) | |||
Anorexia | 5/9 (55.6%) | 35/57 (61.4%) | 31/57 (54.4%) | |||
Calcium, serum-high (hypercalcemia) | 2/9 (22.2%) | 0/57 (0%) | 0/57 (0%) | |||
Calcium, serum-low (hypocalcemia) | 2/9 (22.2%) | 18/57 (31.6%) | 14/57 (24.6%) | |||
Dehydration | 2/9 (22.2%) | 12/57 (21.1%) | 11/57 (19.3%) | |||
Glucose, serum-high (hyperglycemia) | 9/9 (100%) | 27/57 (47.4%) | 29/57 (50.9%) | |||
Glucose, serum-low (hypoglycemia) | 0/9 (0%) | 7/57 (12.3%) | 4/57 (7%) | |||
Magnesium, serum-low (hypomagnesemia) | 2/9 (22.2%) | 5/57 (8.8%) | 5/57 (8.8%) | |||
Pancreatic endocrine: glucose intolerance | 0/9 (0%) | 7/57 (12.3%) | 0/57 (0%) | |||
Phosphate, serum-low (hypophosphatemia) | 2/9 (22.2%) | 4/57 (7%) | 0/57 (0%) | |||
Potassium, serum-high (hyperkalemia) | 2/9 (22.2%) | 11/57 (19.3%) | 4/57 (7%) | |||
Potassium, serum-low (hypokalemia) | 1/9 (11.1%) | 10/57 (17.5%) | 15/57 (26.3%) | |||
Sodium, serum-low (hyponatremia) | 3/9 (33.3%) | 19/57 (33.3%) | 19/57 (33.3%) | |||
Musculoskeletal and connective tissue disorders | ||||||
Muscle weakness, not d/t neuropathy - Extrem-lower | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Muscle weakness, not d/t neuropathy - body/general | 2/9 (22.2%) | 10/57 (17.5%) | 9/57 (15.8%) | |||
Pain - Back | 2/9 (22.2%) | 13/57 (22.8%) | 8/57 (14%) | |||
Pain - Extremity-limb | 0/9 (0%) | 3/57 (5.3%) | 0/57 (0%) | |||
Pain - Joint | 3/9 (33.3%) | 7/57 (12.3%) | 3/57 (5.3%) | |||
Pain - Muscle | 1/9 (11.1%) | 3/57 (5.3%) | 0/57 (0%) | |||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Pain - Tumor pain | 3/9 (33.3%) | 6/57 (10.5%) | 7/57 (12.3%) | |||
Nervous system disorders | ||||||
Dizziness | 2/9 (22.2%) | 8/57 (14%) | 7/57 (12.3%) | |||
Neuropathy: sensory | 1/9 (11.1%) | 9/57 (15.8%) | 4/57 (7%) | |||
Ocular/Visual-Other (Specify) | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Pain - Head/headache | 1/9 (11.1%) | 6/57 (10.5%) | 0/57 (0%) | |||
Syncope (fainting) | 0/9 (0%) | 3/57 (5.3%) | 0/57 (0%) | |||
Taste alteration (dysgeusia) | 3/9 (33.3%) | 21/57 (36.8%) | 16/57 (28.1%) | |||
Tremor | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Psychiatric disorders | ||||||
Confusion | 1/9 (11.1%) | 3/57 (5.3%) | 0/57 (0%) | |||
Insomnia | 2/9 (22.2%) | 10/57 (17.5%) | 12/57 (21.1%) | |||
Mood alteration - agitation | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Mood alteration - anxiety | 1/9 (11.1%) | 11/57 (19.3%) | 8/57 (14%) | |||
Mood alteration - depression | 3/9 (33.3%) | 8/57 (14%) | 5/57 (8.8%) | |||
Renal and urinary disorders | ||||||
Hemorrhage, GU - Urinary NOS | 0/9 (0%) | 0/57 (0%) | 3/57 (5.3%) | |||
Renal failure | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Urinary frequency/urgency | 0/9 (0%) | 5/57 (8.8%) | 0/57 (0%) | |||
Urinary retention (including neurogenic bladder) | 0/9 (0%) | 0/57 (0%) | 4/57 (7%) | |||
Respiratory, thoracic and mediastinal disorders | ||||||
Allergic rhinitis | 0/9 (0%) | 4/57 (7%) | 0/57 (0%) | |||
Cough | 2/9 (22.2%) | 12/57 (21.1%) | 8/57 (14%) | |||
Dyspnea (shortness of breath) | 2/9 (22.2%) | 15/57 (26.3%) | 20/57 (35.1%) | |||
Hemorrhage, pulmonary/upper respiratory - Nose | 1/9 (11.1%) | 9/57 (15.8%) | 0/57 (0%) | |||
Mucositis/stomatitis (clinical exam) - Pharynx | 2/9 (22.2%) | 0/57 (0%) | 0/57 (0%) | |||
Nasal cavity/paranasal sinus reactions | 1/9 (11.1%) | 0/57 (0%) | 0/57 (0%) | |||
Pleural effusion (non-malignant) | 0/9 (0%) | 0/57 (0%) | 4/57 (7%) | |||
Voice changes/dysarthria | 0/9 (0%) | 4/57 (7%) | 0/57 (0%) | |||
Skin and subcutaneous tissue disorders | ||||||
Dermatology/Skin-Other (Specify) | 0/9 (0%) | 5/57 (8.8%) | 0/57 (0%) | |||
Dry skin | 6/9 (66.7%) | 13/57 (22.8%) | 10/57 (17.5%) | |||
Hair loss/Alopecia (scalp or body) | 1/9 (11.1%) | 4/57 (7%) | 10/57 (17.5%) | |||
Nail changes | 0/9 (0%) | 8/57 (14%) | 0/57 (0%) | |||
Pruritus/itching | 2/9 (22.2%) | 12/57 (21.1%) | 4/57 (7%) | |||
Rash/desquamation | 2/9 (22.2%) | 14/57 (24.6%) | 22/57 (38.6%) | |||
Rash: acne/acneiform | 6/9 (66.7%) | 31/57 (54.4%) | 24/57 (42.1%) | |||
Rash: hand-foot skin reaction | 0/9 (0%) | 4/57 (7%) | 0/57 (0%) | |||
Sweating (diaphoresis) | 1/9 (11.1%) | 6/57 (10.5%) | 6/57 (10.5%) | |||
Vascular disorders | ||||||
Hypertension | 1/9 (11.1%) | 4/57 (7%) | 4/57 (7%) | |||
Hypotension | 3/9 (33.3%) | 6/57 (10.5%) | 5/57 (8.8%) | |||
Thrombosis/thrombus/embolism | 0/9 (0%) | 4/57 (7%) | 4/57 (7%) |
Limitations/Caveats
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 | Study Statistician |
---|---|
Organization | SWOG |
Phone | 206-667-4623 |
- NCI-2009-00797
- NCI-2009-00797
- CDR0000586427
- SWOG-S0727
- S0727
- S0727
- U10CA032102