A Study to Learn About the Medicine Ponsegromab in Adults With Cancer of the Pancreas Which Has Spread and Caused Significant Body Weight Loss and Fatigue
Purpose
Study to investigate the efficacy, safety and tolerability of systemic chemotherapy plus ponsegromab versus systemic chemotherapy plus placebo for the first-line treatment in adult participants with cachexia and metastatic pancreatic ductal adenocardinoma.
Conditions
- Cachexia
- Metastatic Pancreatic Ductal Adenocarcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Signed Informed Consent Document - Documented active diagnosis of metastatic pancreatic ductal adenocarcinoma - Cachexia defined by Fearon criteria of weight loss - Completed 1 x 28-day cycle of first-line systemic nab-paclitaxel and gemcitabine chemotherapy or 2 x 14-day cycles of FOLFIRINOX chemotherapy and prior to receiving Cycle 2 chemotherapy - ECOG PS ≤1 with life expectancy of at least 4 months
Exclusion Criteria
- Current active reversible causes of decreased food intake - Cachexia caused by other reasons - Any prior or current clinical diagnosis of heart failure, irrespective of left ventricular ejection fraction or New York Heart Association classification - Left ventricular ejection fraction <50% - Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization - History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody - History of allergy or hypersensitivity to any of the chemotherapeutics or any of their excipients - Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma, symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases - Inadequate liver function - Renal disease requiring dialysis or eGFR <30 mL/min/1.73m2
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Double-Blind ponsegromab Treatment lower dose |
ponsegromab 200 mg subcutaneous injection every 4 weeks |
|
|
Experimental Double-Blind ponsegromab Treatment higher dose |
ponsegromab 400 mg subcutaneous injection every 4 weeks |
|
|
Placebo Comparator Double-Blind Placebo Treatment |
Match placebo subcutaneous injection every 4 weeks |
|
Recruiting Locations
Birmingham, Alabama 35233
Birmingham, Alabama 35294
Bryant, Arkansas 72022
Conway, Arkansas 72034
Little Rock, Arkansas 72205
North Little Rock, Arkansas 72117
Pine Bluff, Arkansas 71603
Encinitas, California 92024
Irvine, California 92612
Irvine, California 92612
La Jolla, California 92037
La Jolla, California 92037
La Jolla, California 92037
La Jolla, California 92037
Los Angeles, California 90048
Los Angeles, California 90095
Orange, California 92868
San Diego, California 92101
San Diego, California 92103
San Diego, California 92103
San Diego, California 92127
Santa Monica, California 90404
Santa Rosa, California 95403
Vista, California 92081
Washington D.C., District of Columbia 20007
Washington D.C., District of Columbia 20007
Athens, Georgia 30607
Honolulu, Hawaii 96813
Honolulu, Hawaii 96813
‘Aiea, Hawaii 96701
Decatur, Illinois 62526
Decatur, Illinois 62526
Hinsdale, Illinois 60521
New Lenox, Illinois 60451
O'Fallon, Illinois 62269
Lenexa, Kansas 66215
Merriam, Kansas 66204
Lexington, Kentucky 40506
Lexington, Kentucky 40536
Lexington, Kentucky 40536
Lexington, Kentucky 40536
Baltimore, Maryland 21205
Baltimore, Maryland 21287
Baltimore, Maryland 21287
Baltimore, Maryland 21287
Kansas City, Missouri 64114
Kansas City, Missouri 64114
Kansas City, Missouri 64132
Omaha, Nebraska 68105
Omaha, Nebraska 68118
Omaha, Nebraska 68198
Reno, Nevada 89502
Reno, Nevada 89502
Reno, Nevada 89502
New Brunswick, New Jersey 08901
New Brunswick, New Jersey 08901
Somerville, New Jersey 08876
Somerville, New Jersey 08876
Rochester, New York 14642
Chapel Hill, North Carolina 27514
Hillsborough, North Carolina 27278
Portland, Oregon 97239
Portland, Oregon 97239
Portland, Oregon 97239
Dallas, Texas 75235
Dallas, Texas 75235
Dallas, Texas 75390
Dallas, Texas 75390
Houston, Texas 77030
Temple, Texas 76508
Seattle, Washington 98101
Seattle, Washington 98109
Seattle, Washington 98195
Dorado, Puerto Rico 00646
Mayagüez, Puerto Rico 00680
Rio Piedras, Puerto Rico 00935
San Juan, Puerto Rico 00909
More Details
- Status
- Recruiting
- Sponsor
- Pfizer
Detailed Description
A Phase 2b/3, randomized, double-blind, multicenter, multinational study to investigate the efficacy, safety and tolerability of systemic chemotherapy plus ponsegromab versus systemic chemotherapy plus placebo for the first-line treatment in adult participants with cachexia and mPDAC. The first-line chemotherapies will either be nab-paclitaxel plus gemcitabine or FOLFIRINOX (or mFOLFIRINOX). The double-blind period is followed by an optional open-label extension period. Initial enrollment will be in Phase 2b. If all eligibility criteria are met, participants will be randomized in a 1:1:1 allocation to study intervention (one of the two doses of ponsegromab, or placebo) plus first-line systemic chemotherapy. Participants must have completed their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-days cycles of FOLFIRINOX) prior to the start of receiving their first dose (Day 1) of study intervention (ponsegromab or placebo). Day 1 study intervention must be taken on the same day participants start their next cycle of nab-paclitaxel and gemcitabine chemotherapy or FOLFIRINOX chemotherapy and prior to receiving chemotherapy. All chemotherapy dosing is to be determined by the participant's health care provider in accordance with local guidelines. Study intervention will be administered Q4W SC. Following enrollment completion of Phase 2b, Phase 3 enrollment will begin, and eligible participants will be randomized in a 1:1:1 allocation to study intervention (one of the two doses of ponsegromab, or placebo). Participants must have completed their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-day cycles of FOLFIRINOX) prior to the start of receiving their first dose (Day 1) of study intervention (ponsegromab or placebo). Day 1 study intervention must be taken on the same day participants start their next cycle of nab-paclitaxel and gemcitabine chemotherapy or FOLFIRINOX chemotherapy and prior to receiving chemotherapy. All chemotherapy dosing is to be determined by the participant's health care provider in accordance with local guidelines. Study intervention will be administered Q4W SC. Once all Phase 2b participants have completed Week 12 procedures, an analysis of Phase 2b will be performed, from which one of the 2 ponsegromab doses will be selected. After the Phase 3 ponsegromab dose has been selected, continuing Phase 2b participants will: - Continue the ponsegromab dose selected for Phase 3 if already randomized to that dose, OR - Be switched to the ponsegromab dose selected for Phase 3 if randomized to the non-selected ponsegromab dose, OR - Continue receiving placebo if randomized to placebo - Remain blinded to study treatment After the ponsegromab dose has been selected, continuing Phase 3 participants will: - Continue the ponsegromab dose selected for Phase 3 if already randomized to that dose, OR - Be switched to the ponsegromab dose selected for Phase 3 if randomized to the non-selected ponsegromab dose, OR - Continue receiving placebo if randomized to placebo - Remain blinded to study treatment Phase 3 participants enrolled after dose selection will be randomized 1:1 (ponsegromab selected dose: placebo). Participants must have completed their first-line pre-randomization systemic chemotherapy (1 x 28-day cycle of nab-paclitaxel and gemcitabine or 2 x 14-days cycles of FOLFIRINOX) prior to the start of receiving their first dose (Day 1) of study intervention (selected Phase 3 ponsegromab dose or placebo). Day 1 study intervention must be taken on the same day participants start their next cycle of nab-paclitaxel and gemcitabine chemotherapy or FOLFIRINOX chemotherapy and prior to receiving chemotherapy. During the Phase 3 portion of the study, there will be an optional sub-study for primary caregivers of participants with cachexia and mPDAC to evaluate the effectiveness of ponsegromab in improving the quality of life and well-being of the primary caregivers. Study intervention (ponsegromab selected dose or placebo) will continue regardless of chemotherapy treatment until permanent discontinuation of study intervention, withdrawal of consent, death, or the end of the Phase 3 double-blind portion of the study has been reached when the approximate number of overall survival events have been accrued for the Phase 3 analysis of overall survival. Participants will have tumor assessments performed approximately every 6 to 8 weeks during the double-blind period by blinded, independent, central reader radiologists. When the number of overall survival events has been accrued to terminate the Phase 3 double-blind portion of the study, active participants can continue in the optional open-label extension where they will receive ponsegromab for up to 12 months.