Metastatic Pancreatic Adenocarcinoma Clinical Trial
Official title:
A Phase 1b/2, Dose-escalation, Randomized, Multicenter Study of Maintenance Ivaltinostat Plus Capecitabine or Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma Whose Disease Has Not Progressed on FOLFIRINOX
This study is a Phase 1b/2, dose-escalation, randomized, multicenter study to assess the efficacy, safety, tolerability, and PK of ivaltinostat in combination with capecitabine and capecitabine monotherapy in patients with metastatic pancreatic adenocarcinoma whose disease has not progressed on a first line fluoropyrimidine-based chemotherapy (e.g., FOLFIRINOX). In Phase 1b, 3 dose levels of ivaltinostat will be studied in combination with a fixed dose of capecitabine to determine the RP2D of ivaltinostat. In Phase 2, patients will be randomized in a 1:1 ratio to the combination of ivaltinostat and capecitabine or to capecitabine monotherapy. A fixed dose for capecitabine 1000 mg/m2 orally twice daily will be taken on Days 1 to 14, and the RP2D of ivaltinostat will be administered intravenously once a week for 2 weeks, followed by 1 week of rest. One cycle consists of 21 days. Tumor response during study treatment will be assessed every 6 weeks up to Cycle 10, then every 9 weeks afterwards using RECIST v1.1 criteria.
Status | Recruiting |
Enrollment | 70 |
Est. completion date | April 2025 |
Est. primary completion date | February 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Age: =18 years - For Phase 1b, histologically or cytologically confirmed pancreatic adenocarcinoma (locally advanced or metastatic) with at least 1 prior therapy in either the advanced or perioperative setting - For Phase 1b, measurable disease and/or non-measurable disease per RECIST v1.1 - For Phase 2, histologically or cytologically confirmed pancreatic adenocarcinoma without evidence of disease progression while receiving initial chemotherapy for metastatic disease (e.g., must have had a demonstrated CR, PR, or SD following initial chemotherapy). - For Phase 2, measurable disease and/or non-measurable or no evidence of disease assessed by baseline CT (or MRI where CT is contraindicated). RECIST v1.1 will be used to allow for assessment of disease progression due to new lesions in patients with no evidence of disease at baseline. Patients with no evidence of disease following FOLFIRINOX chemotherapy will be deemed to have radiographic disease progression if new lesions are detected. - For Phase 2, treatment with FOLFIRINOX for metastatic pancreatic adenocarcinoma at full or modified doses, for a minimum of 16 weeks, and no evidence of progression based on the radiographic imaging. - a. Randomization must occur within 6 weeks of the last dose of chemotherapy. - b. Patients who have received at least 16 weeks of FOLFIRINOX combination regimen but had non-fluoropyrimidine chemotherapeutic agents discontinued prior to 16 weeks due to toxicity are eligible if they have no radiographic evidence of disease. - For Phase 2, patients who received prior chemotherapy or prior chemoradiation for a prior cancer or as adjuvant/neoadjuvant treatment for pancreatic adenocarcinoma are eligible provided at least 12 months have elapsed between the last dose of treatment and initiation of the FOLFIRINOX chemotherapy for metastatic pancreatic adenocarcinoma. - Prior radiation therapy is allowed, provided >14 days have elapsed since completion of radiation prior to randomization. - Adequate organ function - ECOG Performance Status 0-1 at the date of signing the informed consent. Exclusion Criteria: - For Phase 2, radiographic progression of tumor per RECIST 1.1 between start of first line FOLFIRINOX chemotherapy for metastatic pancreatic adenocarcinoma and randomization. - Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or RANKL directed therapy for bone metastases before and during the study as long as these were initiated at least 2 weeks prior to study treatment - For Phase 2, not receiving FOLFIRINOX as initial therapy for metastatic PDAC. Patients who received FOLFIRINOX initially and who needed to discontinue irinotecan or oxaliplatin due to toxicity are eligible, provided they received at least 4 weeks (2 cycles) of FOLFIRINOX - For Phase 2, more than 1 prior line of therapy for metastatic PDAC - Exposure to an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to randomization - Any previous treatment with a HDAC inhibitor, including ivaltinostat |
Country | Name | City | State |
---|---|---|---|
United States | University Cancer and Blood Center | Athens | Georgia |
United States | Roswell Park Comprehensive Cancer Center | Buffalo | New York |
United States | Beacon Cancer Care | Coeur d'Alene | Idaho |
United States | IACT Health | Columbus | Georgia |
United States | The University of Texas Southwestern Medical Center | Dallas | Texas |
United States | Barbara Ann Karmanos Cancer Institute | Detroit | Michigan |
United States | Virginia Cancer Specialists | Fairfax | Virginia |
United States | Penn State Hershey Cancer Institute | Hershey | Pennsylvania |
United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | Community Health Network | Indianapolis | Indiana |
United States | University of Iowa Hospitals and Clinics | Iowa City | Iowa |
United States | Kadlec Regional Medical Center | Kennewick | Washington |
United States | Norton Cancer Institute Audubon | Louisville | Kentucky |
United States | University Medical Center New Orleans | New Orleans | Louisiana |
United States | Clinical Research Alliance | New York | New York |
United States | Hoag Medical Group | Newport Beach | California |
United States | Utah Cancer Specialists | Salt Lake City | Utah |
United States | UCSF Medical Center | San Francisco | California |
United States | UCLA Hematology/Oncology, Gastrointestinal Oncology | Santa Monica | California |
United States | HonorHealth Medical Center | Scottsdale | Arizona |
Lead Sponsor | Collaborator |
---|---|
CG Pharmaceuticals, Inc |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of dose-limiting toxicities (DLTs) in phase 1 | The percentage of subjects who experience a grade 3 or higher adverse event that qualifies as a DLT | 15 months | |
Primary | Incidence of treatment emergent AEs in phase 1 | The number of subjects who experience an adverse event that was possibly related to study drug | 15 months | |
Primary | Treatment emergent changes in clinical laboratory tests in phase 1 | The number of subjects who experience a change in laboratory parameters that was possibly related to study drug. | 15 months | |
Primary | Progression-Free Survival (PFS) in Phase 2 | Investigator assessed PFS | 15 months | |
Secondary | Cmax of ivaltinostat in Phase 1 and 2 | Cmax will be assessed through the maximum measured plasma concentration occurring at Tmax | 19 months | |
Secondary | AUC of ivaltinostat in Phase 1 and 2 | Area under the plasma concentration (AUC) versus time curve from time 0 to time of least measurable concentration | 19 months | |
Secondary | Half-life (T1/2) of ivaltinostat in Phase 1 and 2 | Elimination half life will be calculated | 19 months | |
Secondary | Objective response rate (ORR) in Phase 1 and 2 | ORR per RECIST v1.1 Overall survival (OS). | 19 months | |
Secondary | Incidence of treatment emergent AEs in Phase 2 | The number of subjects who experience an adverse event that was possibly related to study drug | 19 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
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