Combining Ivaltinostat with Capecitabine for Advanced Pancreatic Cancer

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 testing if adding a new drug called ivaltinostat to the standard treatment capecitabine can help people with advanced pancreatic cancer do better than with capecitabine alone.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: CG Pharmaceuticals, Inc (industry)
• Drugs / interventions: chemotherapy, radiation
• Locations: 16 sites (Scottsdale, Arizona and 15 other locations)
• Trial ID: NCT05249101 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of ivaltinostat in combination with capecitabine compared to capecitabine alone in patients with metastatic pancreatic adenocarcinoma who have not progressed after initial chemotherapy. It consists of two phases: the first phase determines the optimal dose of ivaltinostat, while the second phase randomly assigns patients to receive either the combination treatment or capecitabine monotherapy. Patients will undergo regular assessments to monitor tumor response throughout the treatment cycles.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed metastatic pancreatic adenocarcinoma who have shown no disease progression after initial chemotherapy.

Not a fit: Patients who have not received prior chemotherapy or those with rapidly progressing disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with advanced pancreatic cancer by providing a more effective therapeutic option.

How similar studies have performed: While there have been studies on similar combinations, this specific approach is novel and has not been extensively tested.

Eligibility criteria

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

Where this trial is running

Scottsdale, Arizona and 15 other locations

• HonorHealth Research Institute — Scottsdale, Arizona, United States (RECRUITING)
• Hoag Medical Group — Newport Beach, California, United States (RECRUITING)
• UCSF Medical Center — San Francisco, California, United States (RECRUITING)
• UCLA Hematology/Oncology, Gastrointestinal Oncology — Santa Monica, California, United States (RECRUITING)
• University Cancer and Blood Center — Athens, Georgia, United States (RECRUITING)
• Community Health Network — Indianapolis, Indiana, United States (RECRUITING)
• Norton Cancer Institute Audubon — Louisville, Kentucky, United States (RECRUITING)
• University Medical Center New Orleans — New Orleans, Louisiana, United States (RECRUITING)
• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States (RECRUITING)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (RECRUITING)
• Clinical Research Alliance — Westbury, New York, United States (RECRUITING)
• Penn State Hershey Cancer Institute — Hershey, Pennsylvania, United States (RECRUITING)
• The University of Texas Southwestern Medical Center — Dallas, Texas, United States (RECRUITING)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)
• Utah Cancer Specialists — Salt Lake City, Utah, United States (RECRUITING)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: Andrew H. Ko, MD — University of California, San Francisco
• Study coordinator: Glenn C. Michelson, MD

Conditions: Metastatic Pancreatic Adenocarcinoma