Adenocarcinoma of the Pancreas, Advanced Solid Tumors, Cancer, Cancer of Pancreas, Cancer of the Pancreas, Metastases, Metastatic Cancer, Metastatic Pancreatic Cancer, Pancreas Cancer, Pancreatic Cancer, Bone Metastases, Endocrine Cancer, Oncology, Oncology Patients, Solid Tumors, Advanced Malignancy
Conditions
Keywords
pancreas, gemcitabine, metastatic, jaundice
Brief summary
AMG 479 is an investigational fully human monoclonal antibody that targets type 1 insulin-like growth factor receptor (IGF-1R). Signaling through IGF-1R plays an important role in the regulation of cell growth and survival. The primary purpose of the study is to determine if AMG 479 and gemcitabine improves overall survival as compared to placebo and gemcitabine.
Interventions
DRUGAMG 479
AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle
DRUGPlacebo
Placebo administered intravenously on days 1 and 15 of a 28 day cycle
DRUGgemcitabine
gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle
Sponsors
Takeda
NantCell, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Untreated metastatic adenocarcinoma of the pancreas * Adequate hematologic, renal and liver function * Eastern Cooperative Oncology Group (ECOG) 0 or 1
Exclusion criteria
* Prior chemotherapy or radiotherapy for pancreatic cancer * Central nervous system metastases * External biliary drain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine if the Treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in Combination With Gemcitabine Improves Overall Survival as Compared With Placebo in Combination With Gemcitabine in Subjects With Metastatic Adenocarcinoma of the Pancreas | From randomization up to 20 months | The primary endpoint of the study was OS, defined as the time from randomization to death. |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Lithuania, Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Gemcitabine Arm 1: AMG 479-placebo IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle
Placebo: Placebo administered intravenously on days 1 and 15 of a 28 day cycle
gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle | 322 |
| AMG 479 12 mg/kg Dose + Gemcitabine Arm 2: AMG 479 12 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle
AMG 479: AMG 479 12 mg/kg administered intravenously on days 1 and 15 of a 28 day cycle
gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle | 318 |
| AMG 479 20 mg/kg + Gemcitabine Arm 3: AMG 479 20 mg/kg IV days 1 and 15 plus gemcitabine 1000 mg/m2 IV days 1, 8, and 15 of a 28 day cycle
AMG 479: AMG 479 20mg/kg administered intravenously on days 1 and 15 of a 28 day cycle
gemcitabine: gemcitabine 1000mg/m2 administered intravenously on days 1, 8 and 15 of a 28 day cycle | 160 |
| Total | 800 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 202 | 210 | 101 |
| Overall Study | Full Consent withdrawn | 19 | 19 | 11 |
| Overall Study | Lost to Follow-up | 4 | 2 | 2 |
| Overall Study | other event | 7 | 9 | 3 |
Baseline characteristics
| Characteristic | Placebo + Gemcitabine | AMG 479 12 mg/kg Dose + Gemcitabine | AMG 479 20 mg/kg + Gemcitabine | Total |
|---|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.6 | 62.1 years STANDARD_DEVIATION 9.7 | 62.7 years STANDARD_DEVIATION 10.1 | 62.3 years STANDARD_DEVIATION 9.7 |
| Metastatic adenocarcinoma of the pancreas | 322 Participants | 318 Participants | 160 Participants | 800 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 34 Participants | 19 Participants | 14 Participants | 67 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 0 Participants | 7 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 32 Participants | 37 Participants | 17 Participants | 86 Participants |
| Race (NIH/OMB) White | 253 Participants | 258 Participants | 129 Participants | 640 Participants |
| Region of Enrollment Australia | 13 Participants | 7 Participants | 4 Participants | 24 Participants |
| Region of Enrollment Canada | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Region of Enrollment Europe | 216 Participants | 219 Participants | 112 Participants | 547 Participants |
| Region of Enrollment Japan | 30 Participants | 34 Participants | 16 Participants | 80 Participants |
| Region of Enrollment North Asia | 28 Participants | 16 Participants | 13 Participants | 57 Participants |
| Region of Enrollment South America | 5 Participants | 8 Participants | 1 Participants | 14 Participants |
| Region of Enrollment United States | 26 Participants | 31 Participants | 13 Participants | 70 Participants |
| Sex: Female, Male Female | 134 Participants | 159 Participants | 75 Participants | 368 Participants |
| Sex: Female, Male Male | 188 Participants | 159 Participants | 85 Participants | 432 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 202 / 322 | 210 / 318 | 101 / 160 |
| other Total, other adverse events | 312 / 317 | 308 / 315 | 159 / 160 |
| serious Total, serious adverse events | 33 / 317 | 30 / 315 | 18 / 160 |
Outcome results
Primary
Determine if the Treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in Combination With Gemcitabine Improves Overall Survival as Compared With Placebo in Combination With Gemcitabine in Subjects With Metastatic Adenocarcinoma of the Pancreas
The primary endpoint of the study was OS, defined as the time from randomization to death.
Time frame: From randomization up to 20 months
Population: Full analysis set =all randomized subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AMG 479 12 mg/kg Dose + Gemcitabine | Determine if the Treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in Combination With Gemcitabine Improves Overall Survival as Compared With Placebo in Combination With Gemcitabine in Subjects With Metastatic Adenocarcinoma of the Pancreas | 7.0 months |
| AMG 479 20 mg/kg + Gemcitabine | Determine if the Treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in Combination With Gemcitabine Improves Overall Survival as Compared With Placebo in Combination With Gemcitabine in Subjects With Metastatic Adenocarcinoma of the Pancreas | 7.1 months |
| Placebo + Gemcitabine | Determine if the Treatment of AMG 479 at 12 mg/kg and/or 20 mg/kg in Combination With Gemcitabine Improves Overall Survival as Compared With Placebo in Combination With Gemcitabine in Subjects With Metastatic Adenocarcinoma of the Pancreas | 7.2 months |