Ivaltinostat + Capecitabine for Pancreatic Cancer

Recruiting at 21 trial locations

Overseen By Glenn C. Michelson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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 All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for treating pancreatic cancer that has spread. Researchers aim to determine if adding ivaltinostat (CG-745) to the standard drug capecitabine (Xeloda) improves outcomes for patients whose cancer remains stable after initial chemotherapy. Suitable candidates have pancreatic cancer that hasn't progressed following first-line chemotherapy with FOLFIRINOX. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that patients generally tolerate the combination of ivaltinostat and capecitabine well. In studies involving patients who had undergone several treatments, this combination proved safe. For instance, one study demonstrated that patients tolerated the treatment well, supporting the use of ivaltinostat at a specific dose of 250 mg/m². This dose was effective and safe when combined with capecitabine.

The combination treatment has been tested in patients with pancreatic cancer, and results suggest it was both effective and tolerable. Although the combination treatment remains under study, early safety data appears promising. No major safety concerns emerged from these studies, but, like any treatment, side effects can occur.

Those considering joining a trial with this combination should consult a healthcare provider to understand the potential risks and benefits based on the latest findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ivaltinostat and Capecitabine for pancreatic cancer because it offers a unique approach compared to current treatments. Ivaltinostat is a novel drug that targets histone deacetylases (HDACs), which play a role in cancer cell growth and survival. By combining Ivaltinostat with Capecitabine, a chemotherapy drug, there's potential to enhance the overall effectiveness against pancreatic cancer cells. This combination might overcome some resistance seen with standard chemotherapy options like gemcitabine and FOLFIRINOX, offering new hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

This trial will compare two treatment approaches for pancreatic cancer: the combination of ivaltinostat with capecitabine and capecitabine monotherapy. Research has shown that using ivaltinostat with capecitabine may be promising for treating pancreatic cancer. Studies have found that this combination is generally safe for patients, as it doesn't cause severe side effects. The treatment schedule has proven effective and manageable for patients who have already tried other treatments for pancreatic cancer. Ivaltinostat targets enzymes that help cancer cells grow, while capecitabine is a chemotherapy drug that slows or stops cancer cell growth. Together, they aim to enhance treatment effectiveness and improve patient outcomes. ^{1 2 3 4 6}

Who Is on the Research Team?

Andrew H Ko, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 have pancreatic cancer that has spread, and I've had at least one treatment before.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Ivaltinostat

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

CG Pharmaceuticals, Inc

Lead Sponsor

Trials

1

Recruited

70+

Published Research Related to This Trial

In a study of 31 patients with previously treated metastatic pancreatic adenocarcinoma, the combination of docetaxel and capecitabine resulted in a disease control rate of 32.3%, with partial responses in 9.7% of patients and stable disease in 22.6%.

The treatment was associated with a median overall survival of 6.3 months and manageable side effects, including grade III/IV neutropenia in 32.2% of patients, suggesting that this combination may improve quality of life as a second-line chemotherapy option.

NCBI (Pubmed)

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. Katopodis, O., Polyzos, A., Kentepozidis, N., et al.[2018]

Capecitabine, when combined with gemcitabine, shows potential benefits for patients with advanced pancreatic cancer, particularly in those with a good performance status (KPS ≥90), where it improved median survival from 7.5 months to 10.1 months.

While the combination did not significantly improve overall survival compared to gemcitabine alone in the broader patient population, preliminary data suggests it may enhance response rates and survival, indicating a need for further research to fully understand its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine: an evidence-based review of its effectiveness in the treatment of carcinoma of the pancreas. Smith, DB., Neoptolemos, JP.[2021]

In a phase I/II study involving patients with advanced pancreatic ductal adenocarcinoma (PDAC), the combination of the HDAC inhibitor ivaltinostat with gemcitabine and erlotinib showed a promising objective response rate (ORR) of 25% and a disease control rate (DCR) of 93.8%.

The maximum tolerable dose of ivaltinostat was determined to be 250 mg/m2, and the median overall survival (OS) was 8.6 months, indicating that this treatment combination may be a viable option for patients with unresectable PDAC.

NCBI (Pubmed)

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. Jo, JH., Jung, DE., Lee, HS., et al.[2023]

In a phase I study involving 25 patients with localized, inoperable pancreatic adenocarcinoma, capecitabine was found to be well tolerated when given concurrently with radiotherapy, with a recommended dose of 825 mg/m².

The study identified only mild dose-limiting toxicities, such as grade 3 vomiting and fatigue, and no significant hematological toxicities, indicating a favorable safety profile for this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer. Roxburgh, P., Lumsden, GR., Paul, J., et al.[2022]

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, M., et al.[2022]

The maximum tolerated dose (MTD) of vorinostat in combination with capecitabine and radiation for non-metastatic pancreatic cancer was determined to be 400 mg daily, with manageable side effects including lymphopenia and nausea.

Nineteen out of twenty-one patients (90%) experienced stable disease, and the treatment regimen led to a median overall survival of 1.1 years, indicating promising efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. Chan, E., Arlinghaus, LR., Cardin, DB., et al.[2018]

In a Phase I/II study involving 48 patients with solid tumors, mocetinostat combined with gemcitabine showed significant treatment-related toxicities, with 81% of patients experiencing grade ≥3 adverse events, primarily fatigue and thrombocytopenia.

The overall response rate (ORR) was only 11% in the Phase I study, with no responses observed in the Phase II cohort, leading to the conclusion that the combination treatment was not effective enough to continue testing in advanced pancreatic cancer.

NCBI (Pubmed)

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. Chan, E., Chiorean, EG., O'Dwyer, PJ., et al.[2022]

Capecitabine (Xeloda) is an effective treatment for advanced/metastatic breast cancer, showing a response rate of 20% in a phase 2 trial with a median survival time of 452 days for patients who were resistant to previous therapies.

The most common side effects reported were hand-foot syndrome and various blood-related issues, indicating that while Capecitabine can be beneficial, it also carries a risk of significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine. Nishida, M.[2018]

In a study of 42 patients with metastatic or locally advanced pancreatic cancer, capecitabine demonstrated a clinical benefit response in 24% of patients, improving pain intensity and overall performance status.

Capecitabine was generally well tolerated, with a 9.5% objective response rate, suggesting it may be a viable treatment option for further evaluation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. Cartwright, TH., Cohn, A., Varkey, JA., et al.[2022]

In a study of 19 colorectal cancer patients, capecitabine was shown to preferentially convert to 5-fluorouracil (5-FU) in tumor tissues, with 5-FU concentrations in tumors being 3.2 times higher than in adjacent healthy tissues, indicating effective targeting of the drug.

The enzyme thymidine phosphorylase (TP) plays a crucial role in this preferential activation, being significantly more active in colorectal tumors compared to healthy tissue, which helps explain the enhanced efficacy of capecitabine in treating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Schüller, J., Cassidy, J., Dumont, E., et al.[2022]

The combination of mocetinostat and capecitabine significantly reduced cell migration and increased apoptosis in 4T1 breast cancer cells, indicating a potent therapeutic effect when used together.

Lower concentrations of the combined drugs were more effective than higher doses of either drug alone, suggesting that this combination therapy could minimize side effects while maximizing treatment efficacy.

NCBI (Pubmed)

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. Kaya Çakir, H., Eroglu, O.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.742

Safety and preliminary efficacy of ivaltinostat, an HDAC ... The combination of ival and cape was generally well tolerated in this heavily pretreated patient population.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05249101

NCT05249101 | A Study of Ivaltinostat Plus Capecitabine ... This dose schedule was effective and tolerable in the first line setting for patients with pancreatic cancer (Cartwright, 2002). Other Names: Xeloda.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.666

Results of the safety and tolerability of ivaltinostat plus ... Combination therapy of ival with cape has been well tolerated and the safety and PK/PD data support a RP2D of ival of 250 mg/m2.

4. clinicaltrial.be clinicaltrial.be/en/details/32435?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study of Ivaltinostat Plus Capecitabine or ... This dose schedule was effective and tolerable in the first line setting for patients with pancreatic cancer (Cartwright, 2002). Primary ...

5. withpower.com withpower.com/trial/phase-2-pancreatic-adenocarcinoma-metastatic-5-2022-0bf37

Ivaltinostat + Capecitabine for Pancreatic Cancer This trial tests ivaltinostat with capecitabine in patients with advanced pancreatic cancer who have not worsened after initial treatment.

6. firstwordpharma.com firstwordpharma.com/story/5930177

Progress of U.S. Phase 1b/2 Metastatic Pancreatic Cancer ... The safety and efficacy results of the Phase 1b clinical study demonstrated that ivaltinostat can be effectively combined with cytotoxic ...