Cachexia, Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
pancreatic cancer, metastatic cancer, cancer, anorexia, cachexia, weight loss, loss of appetite, fatigue
Brief summary
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.
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.
Interventions
DRUGponsegromab
Double-Blind ponsegromab Treatment
DRUGplacebo
Double-Blind placebo Treatment
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 Key
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline in body weight for ponsegromab compared to placebo | Baseline, Week 12 | — |
| Change from baseline in Functional Assessment of Anorexia/Cachexia Therapy 5-item Anorexia Symptom Scale scores | Baseline, Week 12 | Scale consists of five items, each rated 0-4. Total score ranges from 0 (minimum) to 20 (maximum). Higher scores are associated with a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in non-sedentary physical activity time | Baseline, Week 12 | measured by wearable Digital Health Technology watch |
| Overall survival | Randomization through completion of Phase 3 of the study, an average of 1 year | Outcome defined as the time from randomization to occurrence of all-cause death |
| Change from baseline in body weight (kg) | Baseline, Week 12 and up to Week 52 | — |
| Change from baseline at Week 12 in physical activity as measured by total vector magnitude | Baseline, Week 12 | measured by wearable Digital Health Technology watch |
| Effect on progression free survival | Randomization through completion of Phase 3 of the study, an average of 1 year | determined by Blinded Independent Central Review |
| Effect on objective response rate | Baseline, Week 52 | determined by Blinded Independent Central Review |
| Effect on disease control rate | Baseline, Week 52 | determined by Blinded Independent Central Review |
| Effect on duration of response | Baseline, Week 52 | determined by Blinded Independent Central Review |
| Change from baseline in skeletal muscle area and radiodensity at third lumbar vertebra (L3) | Baseline, Week 12 | measured by CT (or MRI) scan |
| Change from baseline in intermuscular adipose area and radiodensity at L3 | Baseline, Week 12 | measured by CT (or MRI) scan |
| Change from baseline in subcutaneous adipose area and radiodensity at L3 | Baseline, Week 12 | measured by CT (or MRI) scan |
| Change from baseline in visceral adipose area and radiodensity at L3 | Baseline, Week 12 | measured by CT (or MRI) scan |
| Number of participants with incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to permanent discontinuation from study intervention or from study. | Baseline, Week 12 and up to Week 52 | — |
| Number of participants with laboratory test abnormalities. | Baseline, Week 12 and up to Week 52 | — |
| Number of participants with vital signs abnormalities. | Baseline, Week 12 and up to Week 52 | — |
| Change in physical function, assessed on participant completed Patient-Reported Outcomes Measurement Information System Physical Function (version 8c) questionnaire. | Baseline, Week 12 and up to Week 52 | The overall score range for the T-score is 0-100. Higher scores indicate better outcome. |
| Change in fatigue, as assessed on participant completed Patient-Reported Outcomes Measurement Information System - Fatigue (version 7a) questionnaire. | Baseline, Week 12 and up to Week 52 | The overall score range for the T-score is 29.4-83.2. Lower scores indicate better outcome. |
| Occurrence and severity of symptomatic AEs including diarrhea, nausea, vomiting, decreased appetite, fatigue and mouth sores by maximum grade as assessed by the NCI PRO CTCAE. | Baseline, Week 52 | — |
| Change from baseline on ECOG PS | Baseline, Week 12 and up to Week 52 | — |
| Occurrence of chemotherapy dosing changes (including dosing reductions, dosing interruptions, and dosing discontinuations) due to occurrence of the TEAEs of nausea, vomiting, diarrhea, loss of appetite, or fatigue | Baseline, up to Week 52 | — |
| Tumor status | Baseline, Week 12 and up to Week 52 | Assessment of tumor response to treatment as determined by Blinded Independent Central Review assessment per RECIST 1.1 using CT scan (or MRI) |
Countries
Australia, Belgium, Brazil, Bulgaria, Canada, China, France, Germany, India, Israel, Italy, Japan, Mexico, Poland, Puerto Rico, Slovakia, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed