Adenocarcinoma of the Pancreas, Locally Advanced, Unresectable
Conditions
Keywords
Adenocarcinoma, pancreas, pancreatic cancer, local, unresectable, stage II, stage III
Brief summary
This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1). Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.
Detailed description
This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1). Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.
Interventions
DRUGGemcitabine
Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.
DRUGAMG 479
Gemcitabine on days 1, 8, and 15, followed by AMG 479 20 mg/kg on days 1 and 15 of every 28 day cycle.
DRUGPlacebo
Gemcitabine on Days 1, 8, and 15 followed by Placebo 20 mg/kg on days 1 and 15 of every 28 day cycle
Sponsors
NantBioScience, 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
* Subjects must have histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is unresectable, per institutional practice * Radiologically measurable and/or non-measurable disease as defined by RECIST version 1.1 * Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 * Men or women \>/= 18 years of age * Adequate organ function
Exclusion criteria
* Early (stage I) or metastatic (stage IV) disease * Islet cell, acinar cell carcinoma, non-adenocarcinoma, (eg, lymphoma, sarcoma, etc), adenocarcinoma originating from biliary tree or cystadenocarcinoma * External biliary drain * Currently treated or previously treated with biologic, small molecule, immunotherapy, chemotherapy (ie, including gemcitabine), or other agents for pancreatic cancer * Currently treated or previously treated with radiotherapy, or chemoradiotherapy for pancreatic cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint is Progression-free Survival (PFS) as Defined as the Time From Randomization to Progression (Per RECIST v1.1) or Death. | From randomization to the date of either disease progression or death, up to 181 days progression or death | The time from randomization to progression (per RECIST version 1.1) or death from any cause. Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 181 days | OS - time from study day 1 to death (by any cause) |
| Number of Participants With Adverse Events | Up to 4 months | Measured via CTCAE v3.0 |
| Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Up to 181 days | PFS rates - subjects with disease progression (PD) or death at the timepoint; OS rates - subjects alive at the timepoint; ORR - tumor response assessment of either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST); DCR - subjects with PR, CR, or SD Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed |
| Duration of Response | Up to 181 days | DOR - time from the first observation of an objective response (subjects with CR or PR) to the time of PD or death; Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed |
| Number of Participants With Anti-AMG 479 Antibodies | Up to 181 days | post-dose anti-AMG 479 antibody positive rate |
Countries
Austria, Belgium, Czechia, Denmark, Germany, Hungary, Poland, Portugal, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
The Safety Population was used for all summaries (including serious and non-serious adverse events). Only 8/10 subjects received at least 1 dose of protocol-specified treatment and therefore were included in the Safety Population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Gemcitabine Arm 2: AMG479-placebo IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle
Gemcitabine: Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.
Placebo: Gemcitabine on Days 1, 8, and 15 followed by Placebo 20 mg/kg on days 1 and 15 of every 28 day cycle | 5 |
| AMG 479 20 mg/kg + Gemcitabine ARM 1: AMG 479 20mg/kg IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle.
Gemcitabine: Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.
AMG 479: Gemcitabine on days 1, 8, and 15, followed by AMG 479 20 mg/kg on days 1 and 15 of every 28 day cycle. | 3 |
| Total | 8 |
Baseline characteristics
| Characteristic | Total | Placebo + Gemcitabine | AMG 479 20 mg/kg + Gemcitabine |
|---|---|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 11 | 71.6 years STANDARD_DEVIATION 11.8 | 63.0 years STANDARD_DEVIATION 8.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 2 Participants |
| Subjects with locally advanced unresectable adenocarcinoma of the pancreas | 8 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 5 | 0 / 3 |
| other Total, other adverse events | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 1 / 5 | 2 / 3 |
Outcome results
Primary
The Primary Endpoint is Progression-free Survival (PFS) as Defined as the Time From Randomization to Progression (Per RECIST v1.1) or Death.
The time from randomization to progression (per RECIST version 1.1) or death from any cause. Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Time frame: From randomization to the date of either disease progression or death, up to 181 days progression or death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Gemcitabine | The Primary Endpoint is Progression-free Survival (PFS) as Defined as the Time From Randomization to Progression (Per RECIST v1.1) or Death. | NA Months |
| AMG 479 20 mg/kg + Gemcitabine | The Primary Endpoint is Progression-free Survival (PFS) as Defined as the Time From Randomization to Progression (Per RECIST v1.1) or Death. | NA Months |
Secondary
Duration of Response
DOR - time from the first observation of an objective response (subjects with CR or PR) to the time of PD or death; Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed
Time frame: Up to 181 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo + Gemcitabine | Duration of Response | NA Months |
| AMG 479 20 mg/kg + Gemcitabine | Duration of Response | NA Months |
Secondary
Number of Participants With Adverse Events
Measured via CTCAE v3.0
Time frame: Up to 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Gemcitabine | Number of Participants With Adverse Events | 5 Participants |
| AMG 479 20 mg/kg + Gemcitabine | Number of Participants With Adverse Events | 3 Participants |
Secondary
Number of Participants With Anti-AMG 479 Antibodies
post-dose anti-AMG 479 antibody positive rate
Time frame: Up to 181 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo + Gemcitabine | Number of Participants With Anti-AMG 479 Antibodies | 0 Participants |
| AMG 479 20 mg/kg + Gemcitabine | Number of Participants With Anti-AMG 479 Antibodies | 0 Participants |
Secondary
Overall Survival
OS - time from study day 1 to death (by any cause)
Time frame: Up to 181 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Gemcitabine | Overall Survival | NA Months |
| AMG 479 20 mg/kg + Gemcitabine | Overall Survival | NA Months |
Secondary
Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate
PFS rates - subjects with disease progression (PD) or death at the timepoint; OS rates - subjects alive at the timepoint; ORR - tumor response assessment of either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST); DCR - subjects with PR, CR, or SD Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed
Time frame: Up to 181 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Progression Free Survival Rate at 3 months | 2 Participants |
| Placebo + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Progression Free Survival Rate at 6 months | 2 Participants |
| Placebo + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Overall Survival Rate at 3 months | 5 Participants |
| Placebo + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Overall Survival Rate at 6 months | 4 Participants |
| Placebo + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Objective Response Rate | NA Participants |
| Placebo + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Disease Control Rate | NA Participants |
| AMG 479 20 mg/kg + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Objective Response Rate | NA Participants |
| AMG 479 20 mg/kg + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Progression Free Survival Rate at 3 months | 0 Participants |
| AMG 479 20 mg/kg + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Overall Survival Rate at 6 months | 3 Participants |
| AMG 479 20 mg/kg + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Progression Free Survival Rate at 6 months | 0 Participants |
| AMG 479 20 mg/kg + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Disease Control Rate | NA Participants |
| AMG 479 20 mg/kg + Gemcitabine | Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate | Overall Survival Rate at 3 months | 3 Participants |