Sacituzumab Govitecan + Capecitabine for Gastrointestinal Cancer
Recruiting in Detroit (>99 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Henry Ford Health System
Must not be taking: Anticancer biologics, Topoisomerase inhibitors
Disqualifiers: Pregnancy, Active infection, Cardiac disease, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This is a Phase I study to evaluate the safety and tolerability of sacituzumab govitecan in combination with capecitabine for advanced gastrointestinal cancers after progression on standard therapy, and to assess correlation of outcomes with the biomarker Trop-2.
Will I have to stop taking my current medications?
The trial protocol does not clearly specify if you need to stop taking your current medications. However, it mentions that ongoing therapy with certain prohibited medications is not allowed, and prior chemotherapy or targeted therapy must have been stopped at least 2 weeks before enrollment. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug Sacituzumab Govitecan + Capecitabine for gastrointestinal cancer?
Research shows that Capecitabine, a component of the treatment, is effective in treating various gastrointestinal cancers, including colorectal and gastric cancer, when used in combination with other drugs. It has been shown to improve treatment outcomes without increasing toxicity, suggesting potential benefits when combined with Sacituzumab Govitecan.
12345What safety data exists for Sacituzumab Govitecan and Capecitabine in humans?
Capecitabine has been studied in various cancer treatments and can cause side effects like hand-foot syndrome (skin reaction on hands and feet) and neutropenia (low white blood cell count), but it is generally considered tolerable. Sacituzumab Govitecan, also known as Trodelvy, has been used in other cancer treatments, and while specific safety data for gastrointestinal cancer is limited, it has been evaluated for safety in humans.
46789What makes the drug Sacituzumab Govitecan + Capecitabine unique for gastrointestinal cancer?
Sacituzumab Govitecan is unique because it combines an antibody that targets cancer cells with a chemotherapy drug, allowing for more direct delivery of the treatment to cancer cells. This approach is different from traditional chemotherapy, which affects both cancerous and healthy cells, potentially leading to fewer side effects.
48101112Eligibility Criteria
This trial is for adults with advanced gastrointestinal cancers, including gastroesophageal, colorectal, and pancreaticobiliary types that haven't responded to standard treatments. Participants must have proper liver and kidney function, adequate blood counts without support, and agree to use effective contraception methods.Inclusion Criteria
I agree to use birth control as required by the study.
I am a man and will use a condom and spermicide if my partner can have children.
I am 18 or older and can understand and sign a consent form.
+5 more
Exclusion Criteria
Concurrent medical or psychiatric conditions that may confound study interpretation
Medical conditions posing undue risk to patient's participation in the study
Positive serum pregnancy test or women who are breastfeeding
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Treatment
Participants receive sacituzumab govitecan and capecitabine in cycles of 21 days until unacceptable toxicity, disease progression, or other criteria are met
18 months
Multiple visits (in-person) every 21 days
End of Treatment
Participants are assessed for treatment response and any adverse events
1-2 weeks
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
18 months
Regular visits (in-person) as per study protocol
Participant Groups
The study tests the combination of Sacituzumab Govitecan (an antibody-drug conjugate) with Capecitabine (a chemotherapy drug) in patients whose gastrointestinal cancer has progressed after standard therapy. It also looks at how a biomarker called Trop-2 correlates with outcomes.
1Treatment groups
Experimental Treatment
Group I: Sacituzumab govitecan and capecitabineExperimental Treatment2 Interventions
The trial has three dose levels. Dose level -1 has capecitabine at 500mg/m2 twice daily taken orally for two weeks on and one week off, plus sacituzumab govitecan at 7.5mg/kg given intravenously on Days 1 and 8. Each cycle is 21 days. Dose level 0 has capecitabine at 500mg/m2 and sacituzumab govitecan at 10mg/kg. Dose level 1 has capecitabine at 825mg/m2 and sacituzumab govitecan at 10mg/kg.
Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Trodelvy for:
- Metastatic triple-negative breast cancer
- Locally advanced or metastatic urothelial cancer (withdrawn)
- Metastatic HR+/HER2- breast cancer
🇪🇺 Approved in European Union as Trodelvy for:
- Metastatic triple-negative breast cancer
🇨🇦 Approved in Canada as Trodelvy for:
- Metastatic triple-negative breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Henry Ford Cancer-DetroitDetroit, MI
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Who Is Running the Clinical Trial?
Henry Ford Health SystemLead Sponsor
Gilead SciencesIndustry Sponsor
References
Gemcitabine plus capecitabine (Gem-Cape) biweekly in chemorefractory metastatic colorectal cancer. [2022]A proportion of patients with metastatic colorectal cancer (mCRC) are still able to continue with active therapy after their progression to fluoropyrimidines, oxaliplatin, and irinotecan regimens. Studies suggest that gemcitabine and fluoropyrimidines are synergic antimetabolites. The purpose was to evaluate gemcitabine-capecitabine (Gem-Cape) in heavily pretreated mCRC and to thus assess possible predictive factors for progression-free survival (PFS) and overall survival (OS).
Update on capecitabine alone and in combination regimens in colorectal cancer patients. [2020]Capecitabine is an orally administered fluoropyrimidine carbamate which has been developed as a prodrug of 5-FU with the goal to improve its tolerability and intratumoral drug concentration. The review aims to provide an evidence-based update of clinical trials investigating the clinical efficacy, adverse-event profile, dosage and administration of this drug, alone or in combination with conventional chemotherapeutics and/or new target-oriented drugs, in the management of colorectal cancer patients.
Update on capecitabine in colorectal cancer. [2015]In combination chemotherapy for metastatic colorectal cancer, i.v. 5-fluorouracil (5-FU) can be replaced by oral 5-FU (in the form of capecitabine or another orally available analogue) without negatively affecting overall toxicity and without remarkably reducing the efficacy of treatment in terms of response rate or overall survival. Preclinical evidence of synergy has led to promising early and successfully completed studies combining capecitabine plus oxaliplatin with bevacizumab, cetuximab, and epidermal growth factor receptor tyrosine kinase inhibitors. The use of preoperative capecitabine plus radiation is achieving good rates of pathological complete response in rectal cancer. While capecitabine is generally well tolerated, its potential toxicities need careful management and may require individual dose adaption.
Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3 Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naïve Patients with HER2-Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial. [2022]Evidence has suggested that capecitabine-cisplatin is similar or possibly superior to S-1-cisplatin in terms of safety and efficacy for Japanese patients with advanced gastric cancer (AGC).As far as we are aware, our study is the first randomized trial of two regimens consisting of an oral fluoropyrimidine plus cisplatin in human epidermal growth receptor 2-negative AGC patients with measurable lesions.
Phase I study of capecitabine and oxaliplatin in combination with the proteasome inhibitor bortezomib in patients with advanced solid tumors. [2018]The combination of capecitabine and oxaliplatin has clinical benefit in a variety of gastrointestinal malignancies. The proteasome inhibitor bortezomib enhances the cytotoxic activity of fluoropyrimidines and platinum agents in vivo, and targeting of NF-kappaB may overcome chemotherapy resistance. Thus, we performed this phase I study to document the safety and obtain preliminary efficacy data for the combination of capecitabine, oxaliplatin, and bortezomib.
Association of Single-Nucleotide Polymorphisms in Capecitabine Bioactivation Pathway with Adjuvant Therapy Safety in Colorectal Cancer Patients. [2023]Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is part of the standard treatment of colorectal cancer (CRC). Severe adverse dose limiting reactions that impair treatment safety and lead to treatment suspension remain a relevant concern. Single-nucleotide polymorphisms (SNPs) in genes involved in the activation of capecitabine may alter the bioavailability of 5-FU and thereby affect therapy outcomes. The aim of this study was to evaluate the association of these SNPs with severe toxicity and treatment suspension in patients with CRC treated with capecitabine-based therapy. An ambispective cohort study was conducted, including 161 patients with CRC. SNPs were analyzed using real-time PCR with TaqMan® probes. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events v.5.0. CES1 rs71647871-A was associated with a severe hand-foot syndrome (p = 0.030; OR = 11.92; 95% CI = 1.46-73.47; GG vs. A). CDA rs1048977-CC (p = 0.030; OR = 2.30; 95% CI 1.09-5.00; T vs. CC) and capecitabine monotherapy (p = 0.003; OR = 3.13; 95% CI 1.49-6.81) were associated with treatment suspension due to toxicity. SNPs CES1 rs71647871 and CDA rs1048977 may act as potential predictive biomarkers of safety in patients with CRC under capecitabine-based adjuvant therapy.
A phase II study of paclitaxel and capecitabine as a first-line combination chemotherapy for advanced gastric cancer. [2022]Paclitaxel and capecitabine, which have distinct mechanisms of action and toxicity profiles, have each shown high activity as single agents in gastric cancer. Synergistic interaction between these two drugs was suggested by taxane-induced upregulation of thymidine phosphorylase. We, therefore, evaluated the antitumour activity and toxicities of paclitaxel and capecitabine as first-line therapy in patients with advanced gastric cancer (AGC). Patients with histologically confirmed unresectable or metastatic AGC were treated with capecitabine 825 mg m(-2) p.o. twice daily on days 1-14 and paclitaxel 175 mg m(-2) i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities. Between June 2002 and May 2004, 45 patients, of median age 57 years (range=38-73 years), were treated with the combination of capecitabine and paclitaxel. After a median 6 cycles (range=1-9 cycles) of chemotherapy, 43 were evaluable for toxicity and response. A total of 2 patients showed complete response and 20 showed partial response making the overall response rate 48.9% (95% CI=30.3-63.5%). After a median follow-up of 42.2 months (range=31.2-54.3 months), median time to progression was 5.6 months (95% CI=3.9-7.2 months) and median overall survival was 11.3 months (95% CI=8.1-14.4 months). Grade 3 or 4 adverse events include neutropaenia (46.5% of patients), hand-foot syndrome (9.3%), arthralgia (9.3%), and asthenia (4.7%). There was no neutropaenic fever or treatment-related deaths. Paclitaxel and capecitabine combination chemotherapy was active and highly tolerable as a first-line therapy for AGC.
Irinotecan plus capecitabine as a second-line treatment after failure of 5-fluorouracil and platinum in patients with advanced gastric cancer. [2018]This Phase II study was conducted to evaluate the effects of irinotecan plus capecitabine in patients with advanced gastric cancer (AGC) who had received a first-line therapy of 5-fluorouracil/platinum regimen.
A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. [2021]We evaluated the efficacy and safety of cetuximab in combination with XELOX [XELoda® (capecitabine) and OXaliplatin] in advanced gastric cancer (AGC) patients. The objectives were to evaluate overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety of cetuximab plus XELOX.
A phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer. [2022]Capecitabine and docetaxel have considerable single-agent activity in gastric cancer with distinct mechanisms of action and no overlap of key toxicities. A synergistic interaction between these two drugs is mediated by taxane-induced upregulation of thymidine phosphorylase. We investigated the activity and the feasibility of capecitabine and docetaxel combination chemotherapy in patients with previously untreated advanced gastric cancer (AGC). From September 2001 to March 2003, 42 patients with AGC received 21-day cycles of oral capecitabine (1250 mg x m(-2) twice daily on days 1-14) and docetaxel (75 mg x m(-2) i.v. on day 1). The patients received a total of 164 cycles of chemotherapy. The median age was 53.5 years (range 33-73 years). The overall response rate in the 38 efficacy-evaluable patients was 60% (95% confidence interval, 45-74%). The median progression-free survival was 5.2 months (range, 1.0-15.5+ months) and the median overall survival was 10.5 months (range, 2.9-23.7+ months). The most common grade 3/4 adverse events were hand-foot syndrome (HFS: G3 50%), neutropenia (15%) and leucopenia (12%). Further studies of this combination are clearly warranted, albeit with lower doses of both agents (1000 mg x m(-2) twice daily and 60 mg x m(-2)) to reduce the rate of HFS and onycholysis.
Antitumor activities of a novel fluoropyrimidine, N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine (capecitabine). [2019]Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel fluoropyrimidine carbamate that was synthesized for the purpose of finding antitumor drugs with improved safety and efficacy profiles compared with those of 5-fluorouracil (5-FUra) and doxifluridine (5'-deoxy-5-fluorouridine, 5'-dFUrd). The present study compared the antitumor activities of the compound with those of other fluoropyrimidines in 12 human cancer xenograft models and their antimetastatic activities in murine tumor models. The antitumor efficacy of capecitabine was greater than those of 5'-dFUrd, UFT (a mixture of tegafur and uracil) and 5-FUra. Capecitabine was also much safer, particularly much less toxic to the intestinal tract, than the other compounds, indicating higher therapeutic indices. The therapeutic indices of capecitabine, 5'-dFUrd and 5-FUra were >40, >20 and 2.0 against the human CXF280 colon cancer xenograft, the most sensitive line to the fluoropyrimidines so far tested, and 5.1, 1.5, and
Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-fluorouracil: a meta-analysis of published trials. [2022]Capecitabine is an oral fluoropyrimidine that can effectively replace infusional 5-fluorouracil (5-FU) for treatment of colorectal, gastric and breast cancer. This study aims to analyze the incidence and the relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-FU in randomized clinical trials (RCTs).