ZEN003694 + Chemotherapy for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
+22 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
Trial Summary
What is the purpose of this trial?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 with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and that it has progressed on previous standard treatment. ZEN003694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Capecitabine is in a class of medications called antimetabolites. It is taken up by cancer cells and breaks down into fluorouracil, a substance that kills cancer cells. Giving ZEN003694 in combination with capecitabine may be safe in treating patients with metastatic or unresectable solid tumors.
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.
What data supports the effectiveness of the drug ZEN003694 + Chemotherapy for Colorectal Cancer?
Capecitabine, a component of the treatment, has been shown to be effective in treating colorectal cancer, with studies indicating it is at least as effective as traditional 5-FU therapy and associated with fewer side effects. Additionally, capecitabine has demonstrated superior response rates and improved relapse-free survival in various trials.
12345Is the combination of ZEN003694 and chemotherapy safe for humans?
Capecitabine (also known as Xeloda) has been studied for safety in various cancers, including colorectal cancer. It is generally safe but can cause side effects like nausea, diarrhea, and hand-foot syndrome (redness and swelling of the hands and feet).
12567What makes the drug ZEN003694 + Capecitabine unique for colorectal cancer?
The combination of ZEN003694 with Capecitabine is unique because Capecitabine is an oral drug that is selectively activated in tumor cells, mimicking continuous infusion of 5-FU but with more convenience and potentially fewer side effects. ZEN003694 is a novel addition that may enhance the effectiveness of Capecitabine, offering a new approach to treatment.
12357Eligibility Criteria
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)
+19 more
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.
+12 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (ZEN003694, capecitabine)Experimental Treatment7 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Florida Health Science Center - GainesvilleGainesville, FL
University of Cincinnati Cancer Center-UC Medical CenterCincinnati, OH
University of Cincinnati Cancer Center-West ChesterWest Chester, OH
Siteman Cancer Center at Christian HospitalSaint Louis, MO
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. [2022]Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer.
Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. [2022]To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer.
Use of capecitabine in management of early colon cancer. [2021]Capecitabine (Xeloda(®), Roche, Basel, Switzerland) is a pro-drug of 5-fluorouracil (5-FU), and it is converted to 5-FU in the cancer cell by enzymatic degradation. The role of capecitabine in colorectal cancer has evolved in the last 15 years. In early trials in the metastatic setting, capecitabine has shown superior response rates compared with those achieved with 5-FU (Mayo Clinic regimen) (26% vs 17%), with equivalent progression-free survival and overall survival. In the adjuvant setting, the Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) trial demonstrated that capecitabine as a single agent led to improvement in relapse-free survival (hazard ratio: 0.86, 95% confidence interval: 0.74-0.99, P = 0.04) and was associated with significantly fewer adverse events than 5-FU plus leucovorin (LV, folinic acid). On the basis of the X-ACT trial, capecitabine was approved by the United States Food and Drug Administration, the National Institute for Clinical Excellence, and the Scottish Medicines Consortium as monotherapy for the adjuvant treatment of stage III colon cancer. The next step was to incorporate capecitabine into combination therapy. The XELOXA trial studied the combination of capecitabine and oxaliplatin (XELOX) vs 5-FU/LV and demonstrated 5-year disease-free survival of 66% for XELOX, compared with 60% for 5-FU/LV. The toxicity profile was also quite comparable in the two arms. So both the single agent use of capecitabine as well as in combination with oxaliplatin can be considered as part of the standard of care in management of early colon cancer in appropriately selected patient groups.
Xeloda in colorectal cancer. [2015]Xeloda (capecitabine) is a rationally designed, oral pro-drug of 5-fluorouracil (5-FU). It is rapidly and almost completely absorbed in the upper gastrointestinal tract. It is then catabolised in a three-enzyme system, the last step being catalysed by thymidine phosphorylase, which is upregulated in many human cancers. Clinical pharmacology studies have confirmed that this preferential activation actually occurs in human colorectal cancer. Phase I and II trials were performed in colorectal cancer to define the optimal dose and schedule of capecitabine. In two large scale phase III studies this agent has been shown to be at least as effective as a standard regimen of bolus 5-FU and leucovorin (Mayo regimen). Response was superior in the capecitabine arms of these studies with equivalence of progression-free and overall survival. In addition the oral regimen was associated with significantly less toxicity. It seems likely that this agent will replace intravenous 5-FU in the therapy of colorectal cancer and possibly in other cancers.
A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. [2022]Capecitabine (Xeloda) is a novel, oral, selectively tumor-activated fluoropyrimidine with proven activity in the treatment of advanced colorectal cancer. This trial was conducted to evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients.
Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. [2022]Capecitabine (Xeloda) is a fluoropyrimidine which is transformed to 5-fluorouracil (5-FU) at the tumor site. The aim of the present study was to estimate the efficacy of this agent in pretreated patients with advanced breast and colorectal cancer, and to determine the response rate and adverse reactions.
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.