Pancreatic Cancer
Conditions
Keywords
1st-line metastatic pancreatic ductal adenocarcinoma
Brief summary
This is a randomized, double blind, 3 arm (1:1:1) study in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma. The purpose is to test the efficacy and safety of demcizumab, when given in combination with gemcitabine and Abraxane® compared to placebo. The administration of gemcitabine and Abraxane® is a standard treatment for patients with metastatic pancreatic ductal adenocarcinoma.
Interventions
DRUGDemcizumab
administered intravenously
DRUGAbraxane®
administered intravenously
DRUGgemcitabine
administered intravenously
DRUGPlacebo
Sponsors
Celgene Corporation
OncoMed Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have histologically confirmed metastatic pancreatic ductal adenocarcinoma.. Prior chemotherapy and/or radiotherapy either in the adjuvant or neoadjuvant setting or for metastatic disease is not allowed. 2. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue (from either the primary tumor, locoregional disease or a metastatic site), either fresh core-needle-biopsied or archived (two FFPE cores preferred whenever possible). If fresh tissue is obtained, the core biopsy must be done at least 7 days prior to randomization. 3. Age ≥21 years 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5. Measurable disease per RECIST v1.1 5. Adequate organ and marrow function 6. Signed Informed Consent Form 7. For women of childbearing potential, agreement to use two effective forms of contraception
Exclusion criteria
1. Subjects with a neuroendocrine tumor of the pancreas, an acinar tumor of the pancreas or a pancreatic tumor with mixed histologies. 2. Subjects receiving heparin, warfarin, factor Xa inhibitors or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents. 3. Subjects with brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease 4. Subjects with Grade \>2 peripheral neuropathy 5. Subjects with clinically significant ascites 6. Malignancies other than pancreatic cancer successfully treated within 3 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, treated superficial bladder cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent 7. Significant intercurrent illness that will limit the patient's ability to participate in the study or may result in their death over the next 18 months 8. History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy 9. Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease 10. Pregnant women or nursing women 11. Subjects with known HIV infection 12. Known bleeding disorder or coagulopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Investigator-assessed progression-free survival time through duration of the study (2 years, 23 days). | Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm. |
Countries
Australia, Belgium, Canada, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 207 subjects were randomized and 204 subjects were treated in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Placebo Arm Abraxane and gemcitabine plus placebo (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression. | 68 |
| Demcizumab/Placebo Arm Abraxane and gemcitabine plus demcizumab (3 cycles), Abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus placebo (3 cycles), and then Abraxane and gemcitabine until disease progression. | 71 |
| Demcizumab/Demcizumab Arm Abraxane and gemcitabine plus demcizumab (3 cycles), abraxane and gemcitabine (3 cycles), Abraxane and gemcitabine plus demcizumab (3 cycles), and then Abraxane and gemcitabine until disease progression. | 65 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 5 |
| Overall Study | Death | 5 | 4 | 3 |
| Overall Study | Disease progression | 34 | 28 | 34 |
| Overall Study | Other | 8 | 7 | 10 |
| Overall Study | Physician Decision | 2 | 5 | 2 |
| Overall Study | Use of another anticancer therapy | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 1 |
Baseline characteristics
| Characteristic | Placebo/Placebo Arm | Demcizumab/Placebo Arm | Demcizumab/Demcizumab Arm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 37 Participants | 35 Participants | 103 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 34 Participants | 30 Participants | 101 Participants |
| Age, Continuous | 62 years | 63 years | 66 years | 63 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) White | 60 Participants | 70 Participants | 62 Participants | 192 Participants |
| Region of Enrollment Australia | 24 Participants | 13 Participants | 19 Participants | 56 Participants |
| Region of Enrollment Belgium | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Canada | 3 Participants | 5 Participants | 4 Participants | 12 Participants |
| Region of Enrollment Spain | 19 Participants | 31 Participants | 21 Participants | 71 Participants |
| Region of Enrollment United Kingdom | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United States | 17 Participants | 18 Participants | 15 Participants | 50 Participants |
| Sex: Female, Male Female | 27 Participants | 31 Participants | 30 Participants | 88 Participants |
| Sex: Female, Male Male | 41 Participants | 40 Participants | 35 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 68 | 12 / 71 | 3 / 65 |
| other Total, other adverse events | 68 / 68 | 71 / 71 | 65 / 65 |
| serious Total, serious adverse events | 40 / 68 | 49 / 71 | 34 / 65 |
Outcome results
Primary
Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms
Investigator assessed Kaplan-Meier estimates of progression-free survival for placebo/placebo arm and pooled demcizumab arm.
Time frame: Investigator-assessed progression-free survival time through duration of the study (2 years, 23 days).
Population: Placebo/placebo arm and pooled demcizumab arms (ITT population).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo/Placebo Arm | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Progressed (event) | 38 Participants |
| Placebo/Placebo Arm | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Censored, follow-up ended | 3 Participants |
| Placebo/Placebo Arm | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Censored, follow-up ongoing | 22 Participants |
| Placebo/Placebo Arm | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Died (event) | 5 Participants |
| Demcizumab/Placebo and Demcizumab/Demcizumab | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Censored, follow-up ongoing | 47 Participants |
| Demcizumab/Placebo and Demcizumab/Demcizumab | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Progressed (event) | 70 Participants |
| Demcizumab/Placebo and Demcizumab/Demcizumab | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Died (event) | 12 Participants |
| Demcizumab/Placebo and Demcizumab/Demcizumab | Hazard of Progression in the Placebo/Placebo Arm and the Pooled Demcizumab Arms | Censored, follow-up ended | 7 Participants |
Comparison: Efficacy (investigator-assessed Kaplan-Meier estimates of progression-free survival) of placebo/placebo arm to the pooled demcizumab arm (i.e., placebo/placebo arm to demcizumab/placebo and demcizumab/demcizumab arms) in subjects with first-line metastatic pancreatic ductal adenocarcinoma.p-value: =0.715895% CI: [0.63, 1.375]Wilcoxon (Mann-Whitney)