A Study of Ivaltinostat Plus Capecitabine or Capecitabine in Metastatic Pancreatic Adenocarcinoma

NCT05249101 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CG-745-2-08
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• Progression-Free Survival (PFS) in Phase 2

  Investigator assessed PFS

  15 months

Secondary Outcomes (5)

• Cmax of ivaltinostat in Phase 1 and 2

  19 months

• AUC of ivaltinostat in Phase 1 and 2

  19 months

• Half-life (T1/2) of ivaltinostat in Phase 1 and 2

  19 months

• Objective response rate (ORR) in Phase 1 and 2

  19 months

• Incidence of treatment emergent AEs in Phase 2

  19 months

Study Arms (2)

Ivaltinostat plus Capecitabine

EXPERIMENTAL

Ivaltinostat plus Capecitabine

Drug: Ivaltinostat; Drug: Capecitabine

Capecitabine Monotherapy

ACTIVE COMPARATOR

Capecitabine Monotherapy

Drug: Capecitabine

Interventions

Ivaltinostat DRUG

Ivaltinostat (E)-N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalen-1-yloxy)methyl)oct-2-enediamide phosphate) is a novel anticancer therapeutic candidate that inhibits enzymatic activity of histone deacetylase (HDAC).

Ivaltinostat plus Capecitabine

Capecitabine DRUG

Capecitabine is labeled for monotherapy for the treatment of adjuvant Dukes' C colon cancer and metastatic colon cancer at a recommended dose of 1250 mg/m2 twice daily for 2 weeks followed by a 1-week rest. This dose schedule was effective and tolerable in the first line setting for patients with pancreatic cancer (Cartwright, 2002).

Also known as: Xeloda

Capecitabine Monotherapy; Ivaltinostat plus Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CG Pharmaceuticals, Inc: lead

Study Sites (16)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Hoag Medical Group

Newport Beach, California, 92663, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

UCLA Hematology/Oncology, Gastrointestinal Oncology

Santa Monica, California, 90404, United States

Location

University Cancer and Blood Center

Athens, Georgia, 30607, United States

Location

Community Health Network

Indianapolis, Indiana, 46250, United States

Location

Norton Cancer Institute Audubon

Louisville, Kentucky, 40217, United States

Location

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Clinical Research Alliance

Westbury, New York, 11590, United States

Location

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84107, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• Tost J, Ak-Aksoy S, Campa D, Corradi C, Farinella R, Ibanez-Costa A, Dubrot J, Earl J, Melian EB, Kataki A, Kolnikova G, Madjarov G, Chaushevska M, Strnadel J, Tanic M, Tomas M, Dubovan P, Urbanova M, Buocikova V, Smolkova B. Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications. Semin Cancer Biol. 2025 Feb;109:101-124. doi: 10.1016/j.semcancer.2025.01.003. Epub 2025 Jan 23.

  PMID: 39863139 DERIVED

MeSH Terms

Interventions

N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide; Capecitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Andrew H. Ko, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 29, 2022
• First Posted: February 21, 2022
• Study Start: August 15, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

US (16)