Gemcitabine and Nab-Paclitaxel vs Gemcitabine, Nab-Paclitaxel, Durvalumab and Tremelimumab as 1st Line Therapy in Metastatic Pancreatic Adenocarcinoma
Study Details
Study Description
Brief Summary
The standard or usual treatment for this disease consists of two chemotherapy drugs gemcitabine and nab-paclitaxel given together.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Durvalumab is a new type of drug for many types of cancer. Laboratory tests show that it works by allowing the immune system to detect cancer and reactivate the immune response. This may halp to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in a few people and seems promising but it is not clear if it can offer better results than standard treatments alone.
Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. This may also help slow the growth of the cancer cells or may cause cancer cells to die. Tremelimumab has been shown to shrink tumours in animals and has been studied in a few people and seems promising but it is not clear if it can offer better results than standard treatment alone when used with durvalumab.
Combination of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either drug alone and while the combination has been studied in a few people, it is not clear if it can offer better results than standard treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Gemcitabine plus Nab-Paclitaxel Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. |
Drug: Gemcitabine
Drug: Nab-paclitaxel
|
| Experimental: Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. |
Drug: Gemcitabine
Drug: Nab-paclitaxel
Drug: Durvalumab
Drug: Tremelimumab
|
Outcome Measures
Primary Outcome Measures
- Overall Survival [35 months]
Time from randomization to death from any cause with patients who were alive at the time of the final analysis or who became lost to follow-up censored at their last date known to be alive.
Secondary Outcome Measures
- Progression Free Survival [35 months]
Defined as the time from randomization to the first objective documentation of disease progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death due to any cause with patients who had not progressed or died at the time of final analysis censored on the date of the last tumour assessment.
- Objective Response Rate [35 months]
Defined as percentage of participants with objective response over all participants randomized. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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; Objective Response (OR) = CR + PR.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically or cytologically confirmed pancreatic ductal adenocarcinoma which is metastatic.
-
Must have presence of measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).
-
Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease with gemcitabine and nab-paclitaxel.
-
Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit within 4 weeks of randomization to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue of adequate amount and quality in order that the specific correlative marker assays proscribed in the protocol may be conducted.
-
Patient must consent to provision of samples of blood, serum and plasma in order that the specific correlative marker assays proscribed may be conducted.
-
Patients must be ≥ 18 years of age.
-
Patients must have an ECOG performance status of 0 or 1 with a life expectancy of at least 12 weeks.
-
No prior treatment for metastatic disease is permitted. Patients may have received prior adjuvant chemotherapy if the last dose was given more than 6 months prior to recurrence. Patients may not have received chemoradiotherapy or adjuvant radiation therapy. Patient may not have received nab-paclitaxel as adjuvant therapy. Prior systemic treatment for borderline resectable or locally advanced disease is not permitted. Patients receiving a single dose of radiation (up to 8Gy/800RAD) with palliative intent for pain control are eligible provided a minimum of 14 days have elapsed between the radiation and the date of randomization.
-
Adequate normal organ and marrow function as defined below (must be done within 14 days prior to registration).
Absolute neutrophils ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥90 g/L Bilirubin ≤ 1.5 x upper normal limit AST and ALT ≤ 2.5 x upper normal limit Serum creatinine <1.25 UNL or Creatinine clearance ≥40mL/min
-
Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 28 days prior to randomization.
-
Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French.
-
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
-
Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. Patients must agree to return to the participating centre for management of any adverse events which may occur through the course of the trial. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Sites are encouraged to contact CCTG (or their respective Cooperative Group for sites outside Canada) for any questions regarding the interpretation of this criterion. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
-
In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
-
Women/men of childbearing potential must have agreed to use a highly effective contraceptive method
Exclusion Criteria:
-
Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at a low risk of recurrence MAY be eligible. Contact CCTG to discuss eligibility prior to enrolling.
-
Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
-
History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression or prior history of severe (grade 3 or 4) immune-mediated toxicity from other immune therapy.
-
Current or prior use of immunosuppressive medication within 28 days before the first planned dose of study therapy, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
-
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease) diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangitis), rheumatoid arthritis, hypophysitis, uveitis, etc. within the past 3 years prior to the start of treatment.
The following are exceptions to this criterion:
-
Patients with alopecia
-
Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years).
-
Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
-
Patients with active or uncontrolled intercurrent illness including, but not limited to:
-
cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia);
-
active peptic ulcer disease or gastritis;
-
active bleeding diatheses;
-
psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent;
-
known history of previous clinical diagnosis of tuberculosis;
-
known human immunodeficiency virus infection (positive HIV 1/2 antibodies);
-
known active hepatitis B infection (positive HBV surface antigen (HBsAg)). Patients with a past or resolved HBV infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible;
-
known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
-
History of leptomeningeal carcinomatosis.
-
Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
-
Receipt of live attenuated vaccination (examples include, but are not limited to, vaccines for measles, mumps, and rubella, live attenuated influenza vaccine (nasal), chicken pox vaccine, oral polio vaccine, rotavirus vaccine, yellow fever vaccine, BCG vaccine, typhoid vaccine and typhus vaccine) within 30 days prior to randomization.
-
Pregnant or lactating women.
-
Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
-
Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
-
History of hypersensitivity to gemcitabine, nab-paclitaxel, durvalumab or tremelimumab or any excipient.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
| 2 | BCCA - Vancouver Cancer Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 3 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 4 | The Moncton Hospital | Moncton | New Brunswick | Canada | E1C 6Z8 |
| 5 | The Vitalite Health Network - Dr. Leon Richard | Moncton | New Brunswick | Canada | E1C 8X3 |
| 6 | Dr. H. Bliss Murphy Cancer Centre | St. John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 7 | QEII Health Sciences Centre | Halifax | Nova Scotia | Canada | B3H 1V7 |
| 8 | Juravinski Cancer Centre at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8V 5C2 |
| 9 | Kingston Health Sciences Centre | Kingston | Ontario | Canada | K7L 2V7 |
| 10 | Grand River Regional Cancer Centre | Kitchener | Ontario | Canada | N2G 1G3 |
| 11 | London Regional Cancer Program | London | Ontario | Canada | N6A 5W9 |
| 12 | Ottawa Hospital Research Institute | Ottawa | Ontario | Canada | K1H 8L6 |
| 13 | Algoma District Cancer Program | Sault Ste. Marie | Ontario | Canada | P6B 0A8 |
| 14 | Niagara Health System | St. Catharines | Ontario | Canada | L2S 0A9 |
| 15 | Odette Cancer Centre | Toronto | Ontario | Canada | M4N 3M5 |
| 16 | University Health Network | Toronto | Ontario | Canada | M5G 2M9 |
| 17 | St. Joseph's Health Centre | Toronto | Ontario | Canada | M6R 1B5 |
| 18 | Hopital de la Cite-de-la-Sante | Laval | Quebec | Canada | H7M 3L9 |
| 19 | L'Hotel-Dieu de Levis | Levis | Quebec | Canada | G6V 3Z1 |
| 20 | CHUM-Centre Hospitalier de l'Universite de Montreal | Montreal | Quebec | Canada | H2X 3E4 |
| 21 | The Jewish General Hospital | Montreal | Quebec | Canada | H3T 1E2 |
| 22 | The Research Institute of the McGill University | Montreal | Quebec | Canada | H4A 3J1 |
| 23 | Centre Integre Universitaire De Sante Et De Services | Montreal | Quebec | Canada | H4J 1C5 |
| 24 | CHUQ-Pavillon Hotel-Dieu de Quebec | Quebec City | Quebec | Canada | G1R 2J6 |
| 25 | Centre hospitalier universitaire de Sherbrooke | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 26 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
| 27 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
Sponsors and Collaborators
- Canadian Cancer Trials Group
- AstraZeneca
Investigators
- Study Chair: Derek Jonker, Ottawa Hospital Research Institute, ON Canada
Study Documents (Full-Text)
More Information
Publications
None provided.- PA7
Study Results
Participant Flow
| Recruitment Details | From April 10, 2017 to July 28, 2018 in 25 cancer centres in Canada |
|---|---|
| Pre-assignment Detail | There was a run-in phase of this study which accrued the first patient on August 22, 2016, which can be considered as start date of this study. Only patients recruited from April 10, 2017 to July 28, 2018 into the randomized phase II component of the study were included in the analysis. |
| Arm/Group Title | Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Arm/Group Description | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. Gemcitabine Nab-paclitaxel | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. Gemcitabine Nab-paclitaxel Durvalumab Tremelimumab |
| Period Title: Overall Study | ||
| STARTED | 61 | 119 |
| COMPLETED | 61 | 119 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab | Total |
|---|---|---|---|
| Arm/Group Description | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. Gemcitabine Nab-paclitaxel | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. Gemcitabine Nab-paclitaxel Durvalumab Tremelimumab | Total of all reporting groups |
| Overall Participants | 61 | 119 | 180 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
65
|
64
|
65
|
| Age, Customized (Count of Participants) | |||
| Younger than 65 years |
27
44.3%
|
61
51.3%
|
88
48.9%
|
| 65 years or older |
34
55.7%
|
58
48.7%
|
92
51.1%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
35
57.4%
|
52
43.7%
|
87
48.3%
|
| Male |
26
42.6%
|
67
56.3%
|
93
51.7%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
6
9.8%
|
10
8.4%
|
16
8.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
1.7%
|
2
1.1%
|
| White |
55
90.2%
|
105
88.2%
|
160
88.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
2
1.7%
|
2
1.1%
|
| Region of Enrollment (participants) [Number] | |||
| Canada |
61
100%
|
119
100%
|
180
100%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | |||
| 0 |
14
23%
|
27
22.7%
|
41
22.8%
|
| 1 |
47
77%
|
92
77.3%
|
139
77.2%
|
Outcome Measures
| Title | Overall Survival |
|---|---|
| Description | Time from randomization to death from any cause with patients who were alive at the time of the final analysis or who became lost to follow-up censored at their last date known to be alive. |
| Time Frame | 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Arm/Group Description | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. Gemcitabine Nab-paclitaxel | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. Gemcitabine Nab-paclitaxel Durvalumab Tremelimumab |
| Measure Participants | 61 | 119 |
| Median (90% Confidence Interval) [months] |
8.8
|
9.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Gemcitabine Plus Nab-Paclitaxel, Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.72 |
| Comments | a priori threshold for statistical significance was 0.1. | |
| Method | Log Rank | |
| Comments | stratified by ECOG performance status and prior adjuvant therapy. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.94 | |
| Confidence Interval |
(2-Sided) 90% 0.71 to 1.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression Free Survival |
|---|---|
| Description | Defined as the time from randomization to the first objective documentation of disease progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death due to any cause with patients who had not progressed or died at the time of final analysis censored on the date of the last tumour assessment. |
| Time Frame | 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Arm/Group Description | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. Gemcitabine Nab-paclitaxel | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. Gemcitabine Nab-paclitaxel Durvalumab Tremelimumab |
| Measure Participants | 61 | 119 |
| Median (90% Confidence Interval) [months] |
5.4
|
5.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Gemcitabine Plus Nab-Paclitaxel, Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.91 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.98 | |
| Confidence Interval |
(2-Sided) 90% 0.75 to 1.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Objective Response Rate |
|---|---|
| Description | Defined as percentage of participants with objective response over all participants randomized. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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; Objective Response (OR) = CR + PR. |
| Time Frame | 35 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Arm/Group Description | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. Gemcitabine Nab-paclitaxel | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. Gemcitabine Nab-paclitaxel Durvalumab Tremelimumab |
| Measure Participants | 61 | 119 |
| Responded |
14
23%
|
36
30.3%
|
| Not responded |
47
77%
|
83
69.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Gemcitabine Plus Nab-Paclitaxel, Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.28 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | stratified by ECOG performance status and prior adjuvant chemotherapy | |
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.49 | |
| Confidence Interval |
(2-Sided) 90% 0.81 to 2.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | 35 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Only patients who received at least one dose of protocol treatment were included in the evaluation of adverse events. | |||
| Arm/Group Title | Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab | ||
| Arm/Group Description | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Days 1, 8, 15 Q28 days. Gemcitabine Nab-paclitaxel | Gemcitabine 1000 mg/m2 IV & Nab-Paclitaxel 125 mg/m2 until unequivocal progression or unacceptable toxicity. Day 1, 8, 15 Q28 days. plus Durvalumab 1500mg IV day 1 only Q28 days; and Tremelimumab 75 mg IV Days 1 cycles 1, 2, 3 and 4 only until unequivocal progression or unacceptable toxicity. Gemcitabine Nab-paclitaxel Durvalumab Tremelimumab | ||
All Cause Mortality |
||||
| Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 52/58 (89.7%) | 102/119 (85.7%) | ||
Serious Adverse Events |
||||
| Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 26/58 (44.8%) | 82/119 (68.9%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 1/58 (1.7%) | 6/119 (5%) | ||
| Leukocytosis | 0/58 (0%) | 1/119 (0.8%) | ||
| Cardiac disorders | ||||
| Cardiac arrest | 0/58 (0%) | 2/119 (1.7%) | ||
| Heart failure | 1/58 (1.7%) | 0/119 (0%) | ||
| Myocarditis | 0/58 (0%) | 1/119 (0.8%) | ||
| Pericardial effusion | 0/58 (0%) | 1/119 (0.8%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 0/58 (0%) | 1/119 (0.8%) | ||
| Abdominal pain | 6/58 (10.3%) | 5/119 (4.2%) | ||
| Colitis | 0/58 (0%) | 5/119 (4.2%) | ||
| Colonic obstruction | 0/58 (0%) | 1/119 (0.8%) | ||
| Colonic perforation | 0/58 (0%) | 1/119 (0.8%) | ||
| Constipation | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Diarrhea | 1/58 (1.7%) | 3/119 (2.5%) | ||
| Duodenal obstruction | 0/58 (0%) | 1/119 (0.8%) | ||
| Duodenal stenosis | 0/58 (0%) | 2/119 (1.7%) | ||
| Enterocolitis | 0/58 (0%) | 1/119 (0.8%) | ||
| Gastric hemorrhage | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Gastric ulcer | 1/58 (1.7%) | 0/119 (0%) | ||
| Gastrointestinal pain | 0/58 (0%) | 1/119 (0.8%) | ||
| Ileal obstruction | 0/58 (0%) | 1/119 (0.8%) | ||
| Ileus | 0/58 (0%) | 1/119 (0.8%) | ||
| Nausea | 1/58 (1.7%) | 2/119 (1.7%) | ||
| Obstruction gastric | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Other gastrointestinal disorders | 0/58 (0%) | 1/119 (0.8%) | ||
| Pancreatic duct stenosis | 0/58 (0%) | 1/119 (0.8%) | ||
| Pancreatitis | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Proctitis | 0/58 (0%) | 1/119 (0.8%) | ||
| Small intestinal obstruction | 1/58 (1.7%) | 2/119 (1.7%) | ||
| Small intestinal perforation | 0/58 (0%) | 1/119 (0.8%) | ||
| Upper gastrointestinal hemorrhage | 0/58 (0%) | 2/119 (1.7%) | ||
| Vomiting | 1/58 (1.7%) | 5/119 (4.2%) | ||
| General disorders | ||||
| Chills | 0/58 (0%) | 1/119 (0.8%) | ||
| Death NOS | 1/58 (1.7%) | 0/119 (0%) | ||
| Edema limbs | 1/58 (1.7%) | 3/119 (2.5%) | ||
| Edema trunk | 0/58 (0%) | 1/119 (0.8%) | ||
| Fatigue | 1/58 (1.7%) | 5/119 (4.2%) | ||
| Fever | 4/58 (6.9%) | 14/119 (11.8%) | ||
| Sudden death NOS | 0/58 (0%) | 1/119 (0.8%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stenosis | 0/58 (0%) | 6/119 (5%) | ||
| Gallbladder obstruction | 0/58 (0%) | 1/119 (0.8%) | ||
| Hepatic failure | 0/58 (0%) | 1/119 (0.8%) | ||
| Immune system disorders | ||||
| Other immune system disorders | 0/58 (0%) | 8/119 (6.7%) | ||
| Infections and infestations | ||||
| Appendicitis | 0/58 (0%) | 1/119 (0.8%) | ||
| Biliary tract infection | 3/58 (5.2%) | 10/119 (8.4%) | ||
| Catheter related infection | 1/58 (1.7%) | 0/119 (0%) | ||
| Enterocolitis infectious | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Hepatic infection | 0/58 (0%) | 3/119 (2.5%) | ||
| Lung infection | 2/58 (3.4%) | 5/119 (4.2%) | ||
| Other infections and infestations | 0/58 (0%) | 1/119 (0.8%) | ||
| Sepsis | 7/58 (12.1%) | 12/119 (10.1%) | ||
| Skin infection | 0/58 (0%) | 1/119 (0.8%) | ||
| Upper respiratory infection | 0/58 (0%) | 2/119 (1.7%) | ||
| Urinary tract infection | 0/58 (0%) | 2/119 (1.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Aortic injury | 0/58 (0%) | 1/119 (0.8%) | ||
| Fall | 0/58 (0%) | 1/119 (0.8%) | ||
| Hip fracture | 1/58 (1.7%) | 0/119 (0%) | ||
| Spinal fracture | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Investigations | ||||
| Blood bilirubin increased | 0/58 (0%) | 1/119 (0.8%) | ||
| Platelet count decreased | 0/58 (0%) | 1/119 (0.8%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/58 (0%) | 4/119 (3.4%) | ||
| Hypercalcemia | 0/58 (0%) | 1/119 (0.8%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/58 (0%) | 2/119 (1.7%) | ||
| Bone pain | 1/58 (1.7%) | 0/119 (0%) | ||
| Generalized muscle weakness | 2/58 (3.4%) | 1/119 (0.8%) | ||
| Muscle weakness lower limb | 0/58 (0%) | 1/119 (0.8%) | ||
| Nervous system disorders | ||||
| Encephalopathy | 0/58 (0%) | 1/119 (0.8%) | ||
| Ischemia cerebrovascular | 0/58 (0%) | 1/119 (0.8%) | ||
| Lethargy | 0/58 (0%) | 1/119 (0.8%) | ||
| Presyncope | 0/58 (0%) | 2/119 (1.7%) | ||
| Radiculitis | 0/58 (0%) | 1/119 (0.8%) | ||
| Reversible posterior leukoencephalopathy syndrome | 0/58 (0%) | 1/119 (0.8%) | ||
| Stroke | 0/58 (0%) | 3/119 (2.5%) | ||
| Psychiatric disorders | ||||
| Confusion | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Delirium | 0/58 (0%) | 2/119 (1.7%) | ||
| Insomnia | 0/58 (0%) | 1/119 (0.8%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/58 (1.7%) | 2/119 (1.7%) | ||
| Urinary tract obstruction | 0/58 (0%) | 1/119 (0.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Adult respiratory distress syndrome | 0/58 (0%) | 1/119 (0.8%) | ||
| Dyspnea | 1/58 (1.7%) | 9/119 (7.6%) | ||
| Hiccups | 0/58 (0%) | 1/119 (0.8%) | ||
| Pleural effusion | 1/58 (1.7%) | 3/119 (2.5%) | ||
| Pneumonitis | 1/58 (1.7%) | 7/119 (5.9%) | ||
| Pulmonary edema | 1/58 (1.7%) | 1/119 (0.8%) | ||
| Pulmonary fibrosis | 1/58 (1.7%) | 0/119 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Photosensitivity | 0/58 (0%) | 1/119 (0.8%) | ||
| Pruritus | 0/58 (0%) | 2/119 (1.7%) | ||
| Rash maculo-papular | 0/58 (0%) | 4/119 (3.4%) | ||
| Skin ulceration | 0/58 (0%) | 1/119 (0.8%) | ||
| Vascular disorders | ||||
| Hypertension | 0/58 (0%) | 1/119 (0.8%) | ||
| Hypotension | 1/58 (1.7%) | 4/119 (3.4%) | ||
| Other vascular disorders | 0/58 (0%) | 1/119 (0.8%) | ||
| Superficial thrombophlebitis | 0/58 (0%) | 1/119 (0.8%) | ||
| Thromboembolic event | 1/58 (1.7%) | 5/119 (4.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Gemcitabine Plus Nab-Paclitaxel | Gemcitabine + Nab-Paclitaxel + Durvalumab + Tremelimumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 57/58 (98.3%) | 118/119 (99.2%) | ||
| Ear and labyrinth disorders | ||||
| Hearing impaired | 3/58 (5.2%) | 3/119 (2.5%) | ||
| Eye disorders | ||||
| Blurred vision | 2/58 (3.4%) | 12/119 (10.1%) | ||
| Dry eye | 3/58 (5.2%) | 7/119 (5.9%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 4/58 (6.9%) | 10/119 (8.4%) | ||
| Abdominal pain | 45/58 (77.6%) | 93/119 (78.2%) | ||
| Ascites | 3/58 (5.2%) | 5/119 (4.2%) | ||
| Bloating | 2/58 (3.4%) | 14/119 (11.8%) | ||
| Constipation | 33/58 (56.9%) | 80/119 (67.2%) | ||
| Diarrhea | 33/58 (56.9%) | 76/119 (63.9%) | ||
| Dry mouth | 5/58 (8.6%) | 9/119 (7.6%) | ||
| Dyspepsia | 9/58 (15.5%) | 20/119 (16.8%) | ||
| Flatulence | 1/58 (1.7%) | 6/119 (5%) | ||
| Gastroesophageal reflux disease | 10/58 (17.2%) | 17/119 (14.3%) | ||
| Gastrointestinal pain | 1/58 (1.7%) | 6/119 (5%) | ||
| Hemorrhoidal hemorrhage | 3/58 (5.2%) | 0/119 (0%) | ||
| Hemorrhoids | 1/58 (1.7%) | 8/119 (6.7%) | ||
| Mucositis oral | 4/58 (6.9%) | 12/119 (10.1%) | ||
| Nausea | 41/58 (70.7%) | 88/119 (73.9%) | ||
| Other gastrointestinal disorders | 0/58 (0%) | 6/119 (5%) | ||
| Stomach pain | 2/58 (3.4%) | 12/119 (10.1%) | ||
| Vomiting | 28/58 (48.3%) | 60/119 (50.4%) | ||
| General disorders | ||||
| Chills | 6/58 (10.3%) | 19/119 (16%) | ||
| Edema face | 1/58 (1.7%) | 6/119 (5%) | ||
| Edema limbs | 25/58 (43.1%) | 57/119 (47.9%) | ||
| Fatigue | 48/58 (82.8%) | 103/119 (86.6%) | ||
| Fever | 18/58 (31%) | 48/119 (40.3%) | ||
| Flu like symptoms | 5/58 (8.6%) | 15/119 (12.6%) | ||
| Non-cardiac chest pain | 0/58 (0%) | 19/119 (16%) | ||
| Pain | 4/58 (6.9%) | 11/119 (9.2%) | ||
| Infections and infestations | ||||
| Lung infection | 4/58 (6.9%) | 12/119 (10.1%) | ||
| Mucosal infection | 0/58 (0%) | 7/119 (5.9%) | ||
| Skin infection | 8/58 (13.8%) | 16/119 (13.4%) | ||
| Upper respiratory infection | 5/58 (8.6%) | 7/119 (5.9%) | ||
| Urinary tract infection | 7/58 (12.1%) | 9/119 (7.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Bruising | 4/58 (6.9%) | 4/119 (3.4%) | ||
| Fall | 3/58 (5.2%) | 5/119 (4.2%) | ||
| Wound complication | 3/58 (5.2%) | 1/119 (0.8%) | ||
| Investigations | ||||
| Weight loss | 17/58 (29.3%) | 31/119 (26.1%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 35/58 (60.3%) | 76/119 (63.9%) | ||
| Dehydration | 6/58 (10.3%) | 15/119 (12.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 6/58 (10.3%) | 28/119 (23.5%) | ||
| Back pain | 23/58 (39.7%) | 62/119 (52.1%) | ||
| Bone pain | 4/58 (6.9%) | 5/119 (4.2%) | ||
| Flank pain | 4/58 (6.9%) | 7/119 (5.9%) | ||
| Generalized muscle weakness | 7/58 (12.1%) | 16/119 (13.4%) | ||
| Muscle weakness lower limb | 4/58 (6.9%) | 7/119 (5.9%) | ||
| Myalgia | 3/58 (5.2%) | 17/119 (14.3%) | ||
| Pain in extremity | 7/58 (12.1%) | 27/119 (22.7%) | ||
| Nervous system disorders | ||||
| Dizziness | 9/58 (15.5%) | 24/119 (20.2%) | ||
| Dysgeusia | 16/58 (27.6%) | 34/119 (28.6%) | ||
| Headache | 13/58 (22.4%) | 26/119 (21.8%) | ||
| Paresthesia | 7/58 (12.1%) | 17/119 (14.3%) | ||
| Peripheral motor neuropathy | 6/58 (10.3%) | 9/119 (7.6%) | ||
| Peripheral sensory neuropathy | 20/58 (34.5%) | 59/119 (49.6%) | ||
| Somnolence | 0/58 (0%) | 6/119 (5%) | ||
| Psychiatric disorders | ||||
| Anxiety | 9/58 (15.5%) | 33/119 (27.7%) | ||
| Confusion | 2/58 (3.4%) | 8/119 (6.7%) | ||
| Depression | 5/58 (8.6%) | 17/119 (14.3%) | ||
| Insomnia | 17/58 (29.3%) | 53/119 (44.5%) | ||
| Libido decreased | 3/58 (5.2%) | 0/119 (0%) | ||
| Renal and urinary disorders | ||||
| Hematuria | 0/58 (0%) | 7/119 (5.9%) | ||
| Urinary frequency | 5/58 (8.6%) | 6/119 (5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic rhinitis | 5/58 (8.6%) | 12/119 (10.1%) | ||
| Cough | 14/58 (24.1%) | 35/119 (29.4%) | ||
| Dyspnea | 22/58 (37.9%) | 56/119 (47.1%) | ||
| Epistaxis | 12/58 (20.7%) | 22/119 (18.5%) | ||
| Hiccups | 2/58 (3.4%) | 6/119 (5%) | ||
| Nasal congestion | 3/58 (5.2%) | 9/119 (7.6%) | ||
| Pleural effusion | 5/58 (8.6%) | 7/119 (5.9%) | ||
| Pneumonitis | 3/58 (5.2%) | 6/119 (5%) | ||
| Productive cough | 5/58 (8.6%) | 6/119 (5%) | ||
| Sore throat | 3/58 (5.2%) | 11/119 (9.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 28/58 (48.3%) | 64/119 (53.8%) | ||
| Dry skin | 5/58 (8.6%) | 17/119 (14.3%) | ||
| Erythema multiforme | 1/58 (1.7%) | 6/119 (5%) | ||
| Hyperhidrosis | 1/58 (1.7%) | 13/119 (10.9%) | ||
| Nail discoloration | 1/58 (1.7%) | 8/119 (6.7%) | ||
| Other skin and subcutaneous tissue disorders | 1/58 (1.7%) | 10/119 (8.4%) | ||
| Pain of skin | 2/58 (3.4%) | 7/119 (5.9%) | ||
| Pruritus | 6/58 (10.3%) | 29/119 (24.4%) | ||
| Rash acneiform | 3/58 (5.2%) | 15/119 (12.6%) | ||
| Rash maculo-papular | 14/58 (24.1%) | 51/119 (42.9%) | ||
| Vascular disorders | ||||
| Hot flashes | 2/58 (3.4%) | 9/119 (7.6%) | ||
| Hypertension | 7/58 (12.1%) | 11/119 (9.2%) | ||
| Hypotension | 4/58 (6.9%) | 9/119 (7.6%) | ||
| Thromboembolic event | 17/58 (29.3%) | 30/119 (25.2%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Chris O'Callaghan |
|---|---|
| Organization | Canadian Cancer Trials Group |
| Phone | 6135336430 |
| cocallaghan@ctg.queensu.ca |
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