Colon Cancer Clinical Trial

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

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.

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Full Description

There will be approximately 70 (18 Phase 1b dose-escalation, 52 Phase 2 randomized) patients in the study. 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 as specified below:

Arm A

Ivaltinostat (the dose will be selected after reviewing the results of Phase 1b among 3 dose levels of 60, 125, or 250 mg/m2) intravenous infusion over 60 minutes (±10 minutes) once on Days 1 and 8 of a 21-day cycle
Capecitabine 1000 mg/m2 orally twice daily on Days 1 to 14 of a 21-day cycle OR Arm B
Capecitabine 1000 mg/m2 orally twice daily on Days 1 to 14 of a 21-day cycle Study Assessments In Phase 1b, patients will attend clinic visits in Cycle 1 on Days 1, 2, 3, 5, 8, and 15 for assessments, with treatment on Days 1 and 8. After Cycle 1, patients will attend clinic visits on a weekly schedule for treatment (Days 1 and 8) and assessments (Days 1, 8, and 15) during 21-day cycles for the remainder of time receiving study treatment. In Phase 2, patients will attend clinic visits on a weekly schedule for treatment (Days 1 and 8) and assessments (Days 1, 8, and 15) during 21-day cycles.

The Phase 1b will enroll up to 18 patients (6 patients each of 3 dose levels of ivaltinostat [60, 125, and 250 mg/m2] + 1000 mg/m2 capecitabine BID) to assess the combination of ivaltinostat and capecitabine for safety and tolerability as well as to determine the ivaltinostat RP2D, assess the PDy of ivaltinostat, and assess PK parameters of both ivaltinostat and capecitabine. Data from the Phase 1b will be used in safety analyses but not in efficacy analyses.

Tumor response during study treatment will be assessed using RECIST v1.1 criteria. Baseline and on-treatment tumor assessments will be performed using CT or MRI scans with contrast of the chest, abdomen, and pelvis, with other regions as clinically indicated for the assessment of disease. Baseline evaluation should be performed within the 28-day screening period prior to the start of study treatment, as close as possible to randomization. Follow-up assessment consistent with baseline radiologic evaluation (i.e., if CT scan was performed for baseline assessment, then CT scan should be done for the follow-up evaluation) should be performed approximately every 6 weeks (±1 week) until objective disease progression as defined by RECIST v1.1. In addition to the imaging listed above, any other sites with known disease, or at which new disease is suspected, should also be appropriately imaged. Safety evaluations will occur at each protocol-specified study visit.

Patients will continue to receive study treatment until objective radiographic disease progression per RECIST v1.1 as assessed by the Investigator or until unacceptable toxicity occurs.

Once patients have discontinued study treatment, subsequent treatment options will be at the discretion of the treating physician. It is anticipated (but not required) that patients may be retreated with their first line regimen. Patients will be contacted on an approximately every-8-week schedule and followed up for survival. Details of any further anti-cancer treatment will be collected until death, loss to follow up, or withdrawal of consent. In addition to contact every 8 weeks, patients will be contacted in the 7 days following a specified date (data cut-off date) to capture survival status at that point for each survival analysis. Any patient who discontinues study treatment for reasons other than objective radiographic progression should continue to undergo scheduled objective tumor assessments according to the study plan in order to assess objective radiographic progression of disease.

View Eligibility Criteria

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

Study is for people with:

Colon Cancer

Phase:

Phase 1

Estimated Enrollment:

70

Study ID:

NCT05249101

Recruitment Status:

Recruiting

Sponsor:

CG Pharmaceuticals, Inc

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There are 19 Locations for this study

See Locations Near You

HonorHealth Medical Center
Scottsdale Arizona, 85258, United States More Info
Erkut H Borazanci, MD
Principal Investigator
Hoag Medical Group
Newport Beach California, 92663, United States More Info
Tara E Seery, MD
Principal Investigator
UCSF Medical Center
San Francisco California, 94143, United States More Info
Andrew H Ko, MD
Principal Investigator
Evan Walker, MD
Principal Investigator
UCLA Hematology/Oncology, Gastrointestinal Oncology
Santa Monica California, 90404, United States More Info
Joel Randolph Hecht, MD
Principal Investigator
University Cancer and Blood Center
Athens Georgia, 30607, United States More Info
Charles Bodine, MD
Principal Investigator
IACT Health
Columbus Georgia, 31904, United States More Info
Andrew Pippas, MD
Principal Investigator
Beacon Cancer Care
Coeur d'Alene Idaho, 83854, United States More Info
Danko Martincic, MD
Principal Investigator
Community Health Network
Indianapolis Indiana, 46250, United States More Info
Bert H O'Neil, MD
Principal Investigator
University of Iowa Hospitals and Clinics
Iowa City Iowa, 52242, United States More Info
Chandrikha Chandrasekharan, MBBS
Principal Investigator
Norton Cancer Institute Audubon
Louisville Kentucky, 40217, United States More Info
Michael F Driscoll, MD
Principal Investigator
University Medical Center New Orleans
New Orleans Louisiana, 70112, United States More Info
Shou-Ching Tang, MD
Principal Investigator
Barbara Ann Karmanos Cancer Institute
Detroit Michigan, 48201, United States More Info
Anthony Shields, MD, PhD
Principal Investigator
Roswell Park Comprehensive Cancer Center
Buffalo New York, 14263, United States More Info
Christos Fountzilas, MD, FACP
Principal Investigator
Clinical Research Alliance
New York New York, 11590, United States More Info
James T D'Olimpio, MD FACP FAAH
Principal Investigator
Penn State Hershey Cancer Institute
Hershey Pennsylvania, 17033, United States More Info
Nelson S Yee, MD, PhD, RPh
Principal Investigator
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Shubham Pant, MD, MBBS
Principal Investigator
Utah Cancer Specialists
Salt Lake City Utah, 84107, United States More Info
S. DiSean Kendall, MD
Principal Investigator
Virginia Cancer Specialists
Fairfax Virginia, 22031, United States More Info
M. Adham Salkeni, MD, FRCPC
Principal Investigator
Kadlec Regional Medical Center
Kennewick Washington, 99336, United States More Info
Rangaswamy A Chintapatla, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Colon Cancer

Phase:

Phase 1

Estimated Enrollment:

70

Study ID:

NCT05249101

Recruitment Status:

Recruiting

Sponsor:


CG Pharmaceuticals, Inc

How clear is this clinincal trial information?

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