Ivaltinostat + Capecitabine for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

+21 other locations

Overseen by Andrew H Ko, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: CG Pharmaceuticals, Inc

Must be taking: Fluoropyrimidine chemotherapy

Must not be taking: HDAC inhibitors

Disqualifiers: Radiographic progression, Prior HDAC inhibitors, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests ivaltinostat with capecitabine in patients with advanced pancreatic cancer who have not worsened after initial treatment. The goal is to find a safe and effective dose and to see if this combination can better control the cancer. Capecitabine is a medication that is converted into another drug in the body, showing better selectivity and tolerability in tumor tissues.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days before starting the trial. You can continue a stable dose of bisphosphonates or RANKL therapy for bone metastases if started at least 2 weeks before the study.

What data supports the effectiveness of the drug combination Ivaltinostat and Capecitabine for pancreatic cancer?

Research shows that Ivaltinostat, when combined with other drugs like gemcitabine and erlotinib, has shown potential as a treatment option for advanced pancreatic cancer, with some patients experiencing disease control and extended survival. Additionally, Capecitabine is widely used to treat various solid tumors, suggesting its potential effectiveness in combination therapies. ^{1 2 3 4 5}

What safety information is available for the combination of Ivaltinostat and Capecitabine in treating pancreatic cancer?

Capecitabine, also known as Xeloda, has been studied in various trials for pancreatic cancer, showing some common side effects like hand-foot syndrome (skin reaction on palms and soles), low red blood cell count, and high bilirubin levels (a liver-related issue). These studies help understand its safety profile, even though Ivaltinostat-specific safety data is not provided. ^{3 5 6 7 8}

How is the drug Ivaltinostat + Capecitabine unique for treating pancreatic cancer?

The combination of Ivaltinostat and Capecitabine is unique because it pairs a novel drug, Ivaltinostat, with Capecitabine, an oral drug that is activated in tumors to become 5-fluorouracil, potentially enhancing its effectiveness against pancreatic cancer, which is known to be highly resistant to treatment. ^{3 6 9 10 11}

Research Team

Andrew H Ko, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Adults with metastatic pancreatic adenocarcinoma who responded well to initial FOLFIRINOX chemotherapy without disease progression are eligible. They must have adequate organ function, good performance status (ECOG 0-1), and can join within 6 weeks of their last chemo dose. Prior treatments for other cancers or radiation therapy are okay if enough time has passed.

Inclusion Criteria

My cancer can be measured by standard health scans.

I am 18 years old or older.

I've been treated with FOLFIRINOX for pancreatic cancer for at least 16 weeks without the cancer getting worse.

Exclusion Criteria

I have never been treated with a HDAC inhibitor, including ivaltinostat.

I have had more than one treatment for my advanced pancreatic cancer.

My pancreatic cancer has worsened after starting FOLFIRINOX chemotherapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Phase 1b Treatment

Dose-escalation study of ivaltinostat in combination with capecitabine to determine the RP2D

21-day cycles

Clinic visits on Days 1, 2, 3, 5, 8, and 15 in Cycle 1; weekly visits thereafter

Phase 2 Treatment

Randomized study of ivaltinostat plus capecitabine versus capecitabine monotherapy

21-day cycles

Weekly clinic visits for treatment and assessments on Days 1, 8, and 15

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 weeks until disease progression, then every 8 weeks for survival

Treatment Details

Interventions

• Capecitabine (Fluoropyrimidine Analog)
• Ivaltinostat (Histone Deacetylase Inhibitor)

Trial Overview The trial is testing ivaltinostat combined with capecitabine versus capecitabine alone in patients whose cancer hasn't worsened after first-line chemotherapy. It's a two-phase study: the first determines the best dose of ivaltinostat, and the second compares both treatment methods.

Participant Groups

Group I: Ivaltinostat plus Capecitabine Experimental Treatment 2 Interventions

Ivaltinostat plus Capecitabine

Group II: Capecitabine Monotherapy Active Control 1 Intervention

Capecitabine Monotherapy

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

🇺🇸 Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

🇨🇦 Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

🇯🇵 Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Norton Cancer Institute Audubon Louisville, KY

IACT Health Columbus, GA

Penn State Hershey Cancer Institute Hershey, PA

University Cancer and Blood Center Athens, GA

More Trial Locations

Who Is Running the Clinical Trial?

CG Pharmaceuticals, Inc

Lead Sponsor

Trials

1

Patients Recruited

70+

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma. [2023] This phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28-day cycle. In phase II, patients received a six-cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression-free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m2 . In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3-11.2) and 5.3 months (95% CI: 3.7-5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3-16.7)/5.8 (95% CI: 4.6-6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro-MMP10, PECAM1, proMMP-2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC.

2. Iran pubmed.ncbi.nlm.nih.gov

In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting. [2022] Mouse breast cancer cell line 4T1 can accurately mimic the response to immune receptors and targeting therapeutic agents. Combined therapy has emerged as an important strategy with reduced side effects and maximum therapeutic effect. Mocetinostat (MGCD0103) is one of the members of Class I Histone Deacetylase Inhibitors (HDACi) and its mechanism of action has not been defined, yet. Capecitabine (Xeloda) is an antimetabolite and currently is widely utilized to treat a wide range of solid tumors. The aim of this study was to investigate the effects of the capecitabine, mocetinostat and their combined application on the 4T1 cell line.

3. Ireland pubmed.ncbi.nlm.nih.gov

Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. [2018] This single institution phase I trial determined the maximum tolerated dose (MTD) of concurrent vorinostat and capecitabine with radiation in non-metastatic pancreatic cancer.

4. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II study of mocetinostat in combination with gemcitabine for patients with advanced pancreatic cancer and other advanced solid tumors. [2022] To evaluate the safety and efficacy of mocetinostat (a Class I/IV HDAC inhibitor) in combination with gemcitabine in patients with solid tumors, including pancreatic cancer.

5. Germany pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy with capecitabine (Xeloda) and docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial. [2018] To investigate the efficacy and toxicity of the docetaxel and capecitabine combination in patients with previously treated, unresectable adenocarcinoma of the pancreas.

6. United States pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. [2022] To determine the safety and efficacy of capecitabine (Xeloda; Roche Laboratories, Nutley, NJ) in patients with metastatic or unresectable, locally advanced pancreatic cancer.

7. Germany pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. [2022] The purpose of this phase I study was to determine the safety, toxicity, maximum tolerated dose, and pharmacokinetics of capecitabine when administered concurrently with radiotherapy in patients with localised, inoperable pancreatic adenocarcinoma.

8. Japan pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine. [2018] Xeloda (Capecitabine) is a fluorocytidine derivative that is selectively tumor-activated to its cytotoxic moiety, fluorouracil. Capecitabine is readily absorbed from the gastrointestinal tract. In the liver, a 60-kDa carboxylesterase(CE) hydrolyzes much of the compound to 5'-deoxy-5-fluorocytidine (5'-DFCR). Cytidine deaminase(CD), an enzyme found in most tissues, including tumors, subsequently converts 5'-DFCR to 5'-deoxy-5-fluorouridine (5'-DFUR). The enzyme thymidine phosphorylase (TP) then hydrolyzes 5'-DFUR to the active drug 5-FU. It is proved that some human carcinomas express TP in higher concentrations than surrounding normal tissues. In Japan, one of the phase 2 clinical trials tested the efficacy of twice daily oral Capecitabine at 1,657 mg/m(2)/d given for 3 weeks followed by a 1-week rest period and repeated in 4-week cycles in advanced/metastatic breast cancer patients resistant to or recurring during or after docetaxel therapy. The response rate was 20.0% (1 CR, 10 PRs). The median time to progression was 84 days and the median survival time was 452 days. The most common treatment-related adverse events throughout the phase 1 to 2 trials of capecitabine were hand-foot syndrome (50.7%), erythropenia (37.9%), lymphopenia (31.0%), hyperbilirubinemia (33.0%) and so on. Capecitabine is expected to provide a new alternative for the treatment of advanced/metastatic breast cancer.

9. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR [2022] Capecitabine (Xeloda) is an orally administered precursor of 5'deoxy-5-fluorouridine, which is a preferentially activated to 5-fluorouracil in tumors. It is used in the treatment of colorectal, gastric, and breast cancers. Based on a single Phase II trial, which included a total of 4 patients with severe renal impairment (GFR

10. Germany pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. [2022] [corrected] Capecitabine (Xeloda) is a novel fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumors. The purpose of this study was to demonstrate the preferential activation of capecitabine, after oral administration, in tumor in colorectal cancer patients, by the comparison of 5-FU concentrations in tumor tissues, healthy tissues and plasma.

11. New Zealand pubmed.ncbi.nlm.nih.gov

Capecitabine: an evidence-based review of its effectiveness in the treatment of carcinoma of the pancreas. [2021] More than 90% of patients with pancreatic cancer present either with incurable locally advanced or metastatic disease or relapse following surgery. For these patients systemic therapy offers the only prospect of salvage, but pancreatic cancer is one of the most chemoresistant of tumors; current chemotherapy can only delay progression in a limited proportion of patients and survival rates are poor. There is therefore a pressing need for more effective therapy. Capecitabine is a new oral prodrug of fluorouracil, which has shown activity in pancreatic cancer particularly when used in combination with gemcitabine.