ZEN003694 + Chemotherapy for Colorectal Cancer

Recruiting at 31 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Capecitabine

Must not be taking: BET inhibitors, Factor Xa inhibitors

Disqualifiers: CNS disease, DPD deficiency, others

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

Compensation: Varies

Number of Visits: 4

Duration: 21 days per cycle

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and optimal dosage of a new drug, ZEN003694, combined with the chemotherapy drug capecitabine (also known as Xeloda). It focuses on patients with colorectal cancer that has spread or cannot be surgically removed, particularly when standard treatments have failed. ZEN003694 targets proteins that promote tumor cell growth, while capecitabine converts into a cancer-fighting substance inside the body. Individuals with colorectal cancer that has progressed despite previous treatment and who can undergo biopsies might be suitable for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot take certain blood thinners or medications that strongly affect liver enzymes (CYP3A4). You should discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using ZEN003694 with capecitabine might be safe for treating certain cancers. ZEN003694 targets a group of proteins called BET, which help cancer cells grow. Capecitabine is a chemotherapy drug that converts into a substance inside cancer cells to kill them. Together, these drugs aim to stop the growth of tumors that cannot be removed by surgery or have spread to other parts of the body.

As this is a Phase 1 trial, the main goal is to test the safety of this drug combination and determine the best dose. Researchers are assessing how well patients tolerate the treatment and what side effects might occur. Prospective participants should know that Phase 1 trials often mark the first time a treatment is tested in humans, so there is limited information on safety so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ZEN003694 combined with capecitabine for colorectal cancer because ZEN003694 targets a different mechanism than most current treatments. While standard therapies often focus on inhibiting cell division or directly attacking cancer cells, ZEN003694 is a BET inhibitor that disrupts cancer cell growth and survival by interfering with gene expression. This novel approach could offer a new way to treat colorectal cancer, potentially improving outcomes for patients who don't respond well to traditional chemotherapies.

What evidence suggests that ZEN003694 combined with capecitabine might be an effective treatment for metastatic or unresectable colorectal cancer?

Research has shown that ZEN003694, when combined with other cancer drugs, may help treat colorectal cancer that no longer responds to standard treatments. By blocking proteins that promote cancer growth, scientists believe it could be effective. In this trial, participants will receive a combination of ZEN003694 and Capecitabine. Capecitabine, already used to treat colorectal cancer, has been shown in studies to help control the disease in many patients and improve survival rates. Together, these two drugs might offer a new way to manage difficult-to-treat colorectal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Dennis Hsu

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults with metastatic or unresectable cancers that have worsened after standard treatment, including fluorouracil or capecitabine. Participants must be HIV-positive on effective therapy, if applicable, and cannot have used BET inhibitors before. They should not have severe illnesses that could interfere with the study and must agree to use contraception.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I am willing and able to have biopsies before and during treatment.

Total bilirubin =< 1.5 institutional upper limit of normal (ULN)

Exclusion Criteria

I have a stomach or intestine condition that affects how I absorb pills.

I have a known DPD deficiency.

I have recovered from side effects of previous cancer treatments, except for hair loss or mild nerve pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive ZEN003694 orally once daily and capecitabine orally twice daily, 2 weeks on, 1 week off during each treatment cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

Regular visits for CT/MRI, PET/CT, and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up for safety 30 days after the last dose, and then every 3 months for 12 months.

12 months

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• ZEN003694

Trial Overview The trial is testing ZEN003694 combined with usual chemotherapy (capecitabine) to see if it's safe and what the best dose might be for treating advanced solid tumors. ZEN003694 targets proteins involved in tumor growth, while capecitabine interferes with cancer cell DNA.

How Is the Trial Designed?

Group I: Treatment (ZEN003694, capecitabine) Experimental Treatment 7 Interventions

Patients receive ZEN003694 PO QD and capecitabine PO BID 2 weeks on, 1 week off during each treatment cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI, PET/CT, and collection of blood samples throughout the trial. Patients may also undergo biopsies during screening and while on the study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

In a study of 44 previously untreated patients with advanced gastric cancer, capecitabine demonstrated an objective response rate of 34% and a median overall survival of 9.5 months, indicating its efficacy as a first-line treatment.

Capecitabine was generally well tolerated, with the most common side effects being hand-foot syndrome and nausea, and severe myelosuppression was not observed, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Hong, YS., Song, SY., Lee, SI., 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]

In a study of 45 patients with locally advanced rectal cancer, preoperative chemoradiation using capecitabine resulted in significant tumor downstaging, with 63% of primary tumors and 90% of lymph nodes showing downstaging, and a pathologic complete response in 31% of patients.

The treatment was found to be safe and well-tolerated, with no severe hematologic toxicities and manageable Grade 3 side effects, suggesting that capecitabine can effectively enhance surgical options, including sphincter-preserving surgeries for tumors near the anal verge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Kim, JS., Kim, JS., Cho, MJ., et al.[2022]

Capecitabine, a pro-drug converted to 5-fluorouracil in cancer cells, has shown superior response rates compared to traditional 5-FU in metastatic colorectal cancer, with similar overall survival outcomes.

In the adjuvant setting, capecitabine improved relapse-free survival and had fewer adverse events than the combination of 5-FU and leucovorin, leading to its approval as a standard treatment for stage III colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of capecitabine in management of early colon cancer. Hameed, H., Cassidy, J.[2021]

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

Xeloda (capecitabine) is an oral pro-drug that is effectively converted to 5-fluorouracil in the body, particularly in colorectal cancer, where the enzyme needed for activation is more active.

In large phase III trials, capecitabine demonstrated at least equal efficacy to the standard intravenous treatment of 5-FU and leucovorin, with better response rates and significantly lower toxicity, suggesting it may become the preferred treatment for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xeloda in colorectal cancer. Cassidy, J.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3097797/

Capecitabine in the management of colorectal cancer - PMC A trial of 51 patients aged above 70 years found similar results with 67% achieving disease control and only 12% of patients exhibiting grade 3 or 4 toxicity on ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1773224724012140

Capecitabine in the modern management of colon cancer The 5-year survival rate for stage 4 CRC is less than 10 %, most likely because to the low efficacy of existing therapies. According to the American Cancer ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa043116

Capecitabine as Adjuvant Treatment for Stage III Colon ... Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)35639-X/fulltext

Single-agent capecitabine as maintenance therapy after ... This study was to evaluate the efficacy and safety of maintenance therapy with capecitabine versus observation following inductive chemotherapy in patients ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.54

The efficacy of capecitabine as a salvage treatment in ... The median progression free survival (mPFS) and median overall survival (mOS) was 2.77 (95% CI, 2.495-3.045) and 9.60 months (95% CI, 7.625- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05803382

NCT05803382 | Testing the Addition of an Anti-Cancer ... This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with the usual treatment with capecitabine in treating patients ...

7. trialx.com trialx.com/clinical-trials/listings/273750/testing-the-addition-of-an-anti-cancer-drug-zen003694-to-the-usual-chemotherapy-treatment-capecitabine-for-metastatic-or-unresectable-cancers/

Testing the Addition of an Anti-Cancer Drug, ... Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors. Description. PRIMARY OBJECTIVE:.

8. withpower.com withpower.com/trial/phase-1-carcinoma-3-2023-c8482

ZEN003694 + Chemotherapy for Colorectal Cancer Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors. Show more. Will I have to stop ...

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02652

Testing the Addition of an Anti-Cancer Drug, ZEN003694, ... Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors. Eligibility Criteria ...

10. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/colorectal-cancer

Colorectal Cancer clinical trials at University of California Health This phase I trial tests the safety, side effects, and best dose of ZEN003694 in combination with the usual treatment with capecitabine in ...