Evaluation of Efficacy and Safety of Neoadjuvant Treatment With Pamrevlumab in Combination With Chemotherapy (Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX) in Locally Advanced Pancreatic Cancer
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| ClinicalTrials.gov Identifier: NCT03941093 |
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Recruitment Status :
Recruiting
First Posted : May 7, 2019
Last Update Posted : February 25, 2021
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| Condition or disease | Intervention/treatment | Phase |
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| Pancreatic Cancer Non-resectable | Drug: Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX Drug: Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX | Phase 3 |
Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab with either G/NP or FOLFIRINOX, placebo with G/NP or FOLFIRINOX.
Each subject may receive up to six cycles of treatment (each treatment cycle is 28 days). Tumor tissue will be collected during resection to determine surgical outcome and for biomarker analysis. Tumor response will be evaluated by changes in CT scan, FDG-PET, CA 19-9, and NCCN® guidelines.
All subjects randomized will have a safety follow-up visit approximately 28 days after the last dose of study treatment and a final safety follow-up phone call at approximately 60 days after the last dose.
Subjects who complete 6 cycles of treatment will be evaluated for surgical exploration for possible R0 or R1 resection. Surgery will occur at least 4 weeks after the last dose (allowing for a wash-out period from treatment) and only after receipt of the recommendation from the central review board with regards to surgical eligibility. Surgery will occur no longer than 8 weeks after the last dose. Subjects who undergo surgery will be evaluated for surgical complications for at least an additional 90 days following discharge from surgery.
Subjects who are ineligible for surgical exploration (i.e. subjects who did not complete 6 cycles of treatment or do not meet any of the protocol defined criteria or had a contraindication to surgery) will continue in the Follow-up period and receive treatment as per standard of care (SOC) for each institution.
All subjects will be followed for disease progression (if not previously detected) or recurrence following resection (local progression or metastatic disease). Subjects will also be followed for any additional anti-cancer therapy received for their pancreatic cancer. All subjects will be followed for survival (until death) or until the last subject to complete treatment reaches 18 months post-treatment.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 280 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Subjects will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab with G/NP or FOLFIRINOX or placebo with G/NP or FOLFIRINOX. |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double blind |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in Combination With Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients With Locally Advanced, Unresectable Pancreatic Cancer |
| Actual Study Start Date : | May 10, 2019 |
| Estimated Primary Completion Date : | September 2022 |
| Estimated Study Completion Date : | December 2023 |
| Arm | Intervention/treatment |
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Experimental: Arm A
Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX
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Drug: Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX
Drug: Pamrevlumab is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion. Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. Drug: FOLFIRINOX is a combination of several agents administered on Days 1 and 15 of each 28 day treatment cycle via IV infusion. The specific agents are Oxaliplatin, Folinic Acid, Irinotecan, and Fluorouracil. Other Names:
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Placebo Comparator: Arm B
Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX
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Drug: Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX
Drug: Placebo is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion. Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion. Drug: FOLFIRINOX is a combination of several agents administered on Days 1 and 15 of each 28 day treatment cycle via IV infusion. The specific agents are Oxaliplatin, Folinic Acid, Irinotecan, and Fluorouracil. Other Names:
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- Overall Survival (OS) [ Time Frame: Randomization to death due to any cause or until the last subject to complete treatment reaches 18 months post-treatment ]
- Proportion of all randomized subjects in whom R0 or R1 resection is achieved [ Time Frame: After completion of 24 weeks of treatment ]
- Event-free survival (EFS) [ Time Frame: Randomization until one of the following events, whichever occurs first: progression that precludes surgery, local or distant recurrence, death. Assessed up to 6 years. ]
- Change in patient reported outcomes as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 Version 3.0). [ Time Frame: Baseline through safety follow up (~4 weeks post-last dose) ]
The EORTC QLQ-C30 uses for the questions 1 to 28 on a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome.
The EORTC QLQ-C30 uses for the questions 29 and 30 on a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome.
- Patient-Reported Outcomes National Cancer Institute Common Terminology Criteria for Adverse Events (PRO CTCAE) Severity and Interference Items (decreased appetite, nausea, vomiting, diarrhea, abdominal pain and fatigue) [ Time Frame: Baseline through safety follow up (~4 weeks post-last dose) ]
6 item questionnaire with 1-3 questions per item related to frequency, severity and interference
- Frequency answers range from Never to Almost Constantly.
- Severity answers range from None to Very Severe.
- Interference answers range from Not at all to Very much.
- PRO-CTCAE responses are scored from 0 to 4, and there are no standardized scoring rules yet established for how to combine attributes into a single score or how best to analyze PRO-CTCAE data longitudinally.
- PRO-CTCAE scores for each attribute (frequency, severity and/or interference) will be presented descriptively.
- Progression-free survival (PFS) [ Time Frame: Randomization until the last subject to complete treatment reaches 18 months post treatment. ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Understand and sign informed consent; be willing to comply with study procedures, including surgery
- Age ≥ 18 years
- Be a male, or non-pregnant and non-lactating female
- Negative serum B-hCG pregnancy test at screening for women of childbearing potential
- Male subjects with partners of childbearing potential and female subjects of childbearing potential are required to use highly effective contraception methods during the conduct of the study and for 6 months after the last dose of study drug
- Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC)
- Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2018 as determined by central imaging
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria as determined by central imaging
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN), alkaline phosphatase <2.5 x ULN, and bilirubin ≤1.5 x ULN or in subjects with biliary stenting ≤2.0 x ULN
- Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin >9.0 g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3
- Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min
- Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
Exclusion Criteria:
- Prior chemotherapy or radiation for pancreatic cancer
- Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
- Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted.
- History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
- History of allergy or hypersensitivity to any of the chemotherapy agents being prescribed or their excipients
- Any medical or surgical condition that may place the subject at increased risk while on study
- Any condition potentially decreasing compliance to study procedures
- Exposure to another investigational drug within 28 days of first dosing visit, or 5 half-lives of the investigational drug (whichever is longer)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infections, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Documented history of drug or alcohol abuse within 6 months of signing informed consent
- Any medical condition that, in the opinion of the investigator, may pose a safety risk to a subject in this trial, may confound the assessment of safety and efficacy, or may interfere with study participation
- Subjects with a history of; interstitial pulmonary disease, HCV, HBV or HIV infection
- Subjects who have been administered a live vaccine within four weeks prior to the first administration of therapy
- Subjects who cannot stop chronic medications that inhibit or induce CYP2C8 or CYP3A4
- Subjects with poorly controlled comorbid conditions, including; congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited function
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03941093
| Contact: Mairead Carney | 415-978-1337 | lapis@fibrogen.com |
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| Responsible Party: | FibroGen |
| ClinicalTrials.gov Identifier: | NCT03941093 |
| Other Study ID Numbers: |
FGCL-3019-087 |
| First Posted: | May 7, 2019 Key Record Dates |
| Last Update Posted: | February 25, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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locally advanced pancreatic cancer unresectable pancreatic cancer |
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Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Leucovorin Gemcitabine Paclitaxel Albumin-Bound Paclitaxel Irinotecan Fluorouracil Folfirinox |
Levoleucovorin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |