Sacituzumab Govitecan + Capecitabine for Gastrointestinal Cancer

Overseen By Maria Diab, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Henry Ford Health System

Must not be taking: Anticancer biologics, Topoisomerase inhibitors

Disqualifiers: Pregnancy, Active infection, Cardiac disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 23

Duration: 18 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced gastrointestinal cancers, such as stomach, colon, or pancreatic cancer, that have not responded to standard treatments. The focus is on the safety and tolerability of using sacituzumab govitecan (an antibody-drug conjugate) with capecitabine (a chemotherapy drug) and whether the results relate to the specific biomarker, Trop-2. The trial suits those who have tried other treatments without success and have cancers that have spread. Participants must have good general health in terms of blood, liver, and kidney function. 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 combination.

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.

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

Research has shown that sacituzumab govitecan is a targeted therapy approved for treating certain breast cancers. It targets Trop-2 receptors on cancer cells. This same target is under study in gastrointestinal cancer. Sacituzumab govitecan has consistently shown safety in previous studies, particularly for breast cancer. Common side effects include low blood cell counts, diarrhea, nausea, and fatigue, which can usually be managed with medical help.

Capecitabine, the other drug in this trial, is already approved for treating various cancers, including breast and colorectal cancer. Its side effects can include diarrhea, nausea, and a skin reaction on the hands and feet known as hand-foot syndrome. Most patients manage these side effects well.

As this is a Phase 1 trial, the main goal is to assess the safety and tolerability of these drugs when used together. The trial tests different dose levels to find the safest and most effective combination. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for gastrointestinal cancer?

Researchers are excited about sacituzumab govitecan combined with capecitabine for gastrointestinal cancer because this treatment pairs an innovative antibody-drug conjugate with a chemotherapy agent. Sacituzumab govitecan targets and delivers a powerful chemotherapy directly to tumor cells, potentially minimizing damage to healthy cells compared to traditional chemotherapy. This targeted approach differs from standard treatments like FOLFOX or FOLFIRI, which often affect both cancerous and healthy cells. Additionally, the combination with capecitabine, an oral chemotherapy drug, could offer a more convenient treatment regimen, enhancing patient quality of life.

What evidence suggests that sacituzumab govitecan and capecitabine could be effective for gastrointestinal cancer?

Research has shown that sacituzumab govitecan is a targeted treatment that binds to Trop-2 receptors on cancer cells, delivering a drug to destroy them. Studies have found it effective for certain cancers, such as advanced triple-negative breast cancer. Capecitabine, a chemotherapy drug, treats various cancers, including colorectal cancer. In this trial, participants will receive a combination of sacituzumab govitecan and capecitabine, which is expected to enhance their ability to fight cancer, particularly in advanced gastrointestinal cancers unresponsive to standard treatments. Early results suggest this combination could be promising, but further research is needed to confirm its effectiveness for this type of cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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 am a man and will use a condom and spermicide if my partner can have children.

I agree to use birth control as required by the study.

Willing and able to comply with the requirements and restrictions in this protocol

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Sacituzumab Govitecan

Trial Overview 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.

How Is the Trial Designed?

Group I: Sacituzumab govitecan and capecitabine Experimental Treatment 2 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

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In a study of 161 colorectal cancer patients, specific genetic variations (SNPs) in the CES1 and CDA genes were linked to severe side effects from capecitabine, a common cancer treatment, indicating that these SNPs could help predict which patients might experience serious toxicity.

The CES1 rs71647871 SNP was particularly associated with a high risk of severe hand-foot syndrome, while the CDA rs1048977 SNP and capecitabine monotherapy were linked to a higher likelihood of treatment suspension due to toxicity, highlighting the importance of genetic testing for personalized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Single-Nucleotide Polymorphisms in Capecitabine Bioactivation Pathway with Adjuvant Therapy Safety in Colorectal Cancer Patients. Cura, Y., Sánchez-Martín, A., Márquez-Pete, N., et al.[2023]

In a phase II study involving 84 patients with HER2-negative advanced gastric cancer, capecitabine-cisplatin did not show superior efficacy compared to S-1-cisplatin, with response rates of 53.5% and 51.2% respectively.

Capecitabine-cisplatin was associated with a higher incidence of severe side effects, such as anorexia and fatigue, suggesting that S-1-cisplatin should remain the preferred first-line treatment in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Kawakami, H., Takeno, A., Endo, S., et al.[2022]

The combination of paclitaxel and capecitabine as first-line therapy for advanced gastric cancer showed a promising overall response rate of 48.9%, with 2 patients achieving complete response and 20 achieving partial response after a median of 6 treatment cycles.

This treatment was well-tolerated, with no treatment-related deaths and manageable side effects, including neutropenia in 46.5% of patients, indicating that it is both effective and safe for patients with advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel and capecitabine as a first-line combination chemotherapy for advanced gastric cancer. Kang, HJ., Chang, HM., Kim, TW., et al.[2022]

In a Phase II study involving 48 patients with advanced gastric cancer, the combination of irinotecan and capecitabine resulted in a partial response rate of 27.1%, indicating its potential effectiveness as a second-line treatment after initial therapy.

The treatment was generally well-tolerated, with manageable side effects; however, 17.4% of patients experienced Grade 3 diarrhea, and there were no treatment-related deaths, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus capecitabine as a second-line treatment after failure of 5-fluorouracil and platinum in patients with advanced gastric cancer. Sun, Q., Hang, M., Xu, W., et al.[2018]

In a study of 44 previously untreated patients with advanced gastric cancer, the combination of cetuximab and XELOX chemotherapy resulted in a significant overall response rate of 52.3%, with median progression-free survival of 6.5 months and overall survival of 11.8 months.

The treatment was generally safe, with most side effects being mild to moderate (grade 1 or 2), such as anemia and asthenia, and serious hematologic toxicities were rare, indicating that cetuximab combined with XELOX is a viable first-line option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Kim, C., Lee, JL., Ryu, MH., et al.[2021]

The combination of capecitabine and docetaxel in treating advanced gastric cancer showed a promising overall response rate of 60% among 38 patients, indicating effective synergy between the two drugs.

While the treatment was effective, it also led to significant side effects, particularly hand-foot syndrome in 50% of patients, suggesting that future studies should explore lower doses to minimize toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer. Park, YH., Ryoo, BY., Choi, SJ., et al.[2022]

Capecitabine demonstrated greater antitumor efficacy compared to other fluoropyrimidines like 5-FUra and 5'-dFUrd in 12 human cancer xenograft models, indicating its potential as a more effective cancer treatment.

It also showed a significantly improved safety profile, being much less toxic to the intestinal tract, which suggests a higher therapeutic index, especially in sensitive cancer models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activities of a novel fluoropyrimidine, N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine (capecitabine). Ishikawa, T., Fukase, Y., Yamamoto, T., et al.[2019]

Capecitabine, an oral cancer treatment, is associated with a higher incidence of severe diarrhoea (16.6%) compared to infusional 5-fluorouracil (5-FU) (12.7%), with a relative risk of 1.39 based on a review of 23 studies involving 15,761 patients.

In colorectal cancer patients specifically, the risk of severe diarrhoea increases to 17.0% for capecitabine versus 12.9% for 5-FU, and the risk is significantly higher when combined with irinotecan, which has a relative risk of 2.35.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-fluorouracil: a meta-analysis of published trials. Iacovelli, R., Pietrantonio, F., Palazzo, A., et al.[2022]

In a study of 119 heavily pretreated patients with metastatic colorectal cancer, the combination of gemcitabine and capecitabine (Gem-Cape) showed a clinical benefit rate of 44.53%, with median progression-free survival (PFS) of 2.87 months and overall survival (OS) of 6.53 months.

The treatment was generally well-tolerated, with most side effects being mild (grades 1-2), and no treatment-related deaths or discontinuations, indicating that Gem-Cape is a feasible option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus capecitabine (Gem-Cape) biweekly in chemorefractory metastatic colorectal cancer. Jiménez-Fonseca, P., Solis, MP., Garrido, M., et al.[2022]

Oral 5-fluorouracil (capecitabine) can effectively replace intravenous 5-FU in chemotherapy for metastatic colorectal cancer without increasing overall toxicity or significantly reducing treatment efficacy, based on preclinical and early clinical studies.

Capecitabine combined with radiation shows promising results in achieving high rates of pathological complete response in rectal cancer, although careful management of its potential toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on capecitabine in colorectal cancer. Schmoll, HJ., Arnold, D.[2015]

Capecitabine is an oral medication designed to improve the tolerability and effectiveness of 5-FU in treating colorectal cancer by increasing drug concentration within tumors.

The review focuses on clinical trials that assess capecitabine's efficacy, side effects, and its use alone or with other chemotherapy agents, highlighting its role in managing colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on capecitabine alone and in combination regimens in colorectal cancer patients. Silvestris, N., Maiello, E., De Vita, F., et al.[2020]

The combination of capecitabine, oxaliplatin, and bortezomib was found to be safe, with no dose-limiting toxicities observed at any bortezomib dose level in a phase I study involving 13 patients.

Preliminary results showed some antitumor activity, with three objective tumor responses noted, suggesting that this combination therapy could be further evaluated for effectiveness in treating gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of capecitabine and oxaliplatin in combination with the proteasome inhibitor bortezomib in patients with advanced solid tumors. Cohen, SJ., Engstrom, PF., Lewis, NL., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11554802/

Efficacy and safety of sacituzumab govitecan Trop-2- ... Sacituzumab govitecan (SG) is a promising Trop-2-targeted antibody-drug conjugate (ADC) approved for the treatment of metastatic triple-negative ...

2. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/sacituzumab-govitecan-in-combination-with-capecitabine-for-advanced-gastrointestinal-cancers-after-progression-on-standard-therapy/

Sacituzumab Govitecan in Combination With Capecitabine ... Sacituzumab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as Trop-2 receptors, and delivers ...

3. askgileadmedical.com askgileadmedical.com/docs/trodelvy/trodelvy-use-in-patients-with-brain-metastases-in-metastatic-breast-cancer-studies

Trodelvy® (sacituzumab govitecan-hziy) Use in Patients ... An open-label, phase 2 study (NCT04647916) is evaluating the efficacy and safety of SG in HER2- breast cancer that has metastasized to the brain. Clinical Data ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)01177-9/fulltext

Effectiveness of sacituzumab govitecan and management ... We describe the real-world effectiveness of SG as 2L+ mTNBC treatment and the proportion of patients with neutropenia and its management.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12231463/

Efficacy and safety of Sacituzumab govitecan in solid tumors Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) that targets trophoblast cell-surface antigen 2 and is conjugated to SN-38, a potent ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06926920?intr=Sacituzumab%20govitecan%20%20OR%20GS0132%20OR%20%20hRS7SN38%20antibody%20drug%20conjugate%20OR%20%20IMMU0132%20OR%20%20IMMU132%20OR%20%20Isactuzumab%20govitecan%20OR%20%20Sacituzumab%20govitecanhziy%20TRODELVY%20OR%20%20Trodelvy%20OR%20%20TROP2SN38&aggFilters=phase:2%203,status:rec%20not%20act&rank=6

A Study of Sacituzumab Govitecan Given at an Alternative ... A Study of Sacituzumab Govitecan Given at an Alternative Dose and Schedule in Participants With Advanced Triple-Negative Breast Cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11648803/

Safety profile of sacituzumab govitecan in patients with breast ... This systematic review and meta-analysis provides extensive data on the safety and management of SG toxicity in BC patients across clinical trials.