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

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. ^{1 2 3 4 5}

What 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. ^{4 6 7 8 9}

What 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. ^{4 8 10 11 12}

Eligibility 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.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Gemcitabine plus capecitabine (Gem-Cape) biweekly in chemorefractory metastatic colorectal cancer. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Update on capecitabine alone and in combination regimens in colorectal cancer patients. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Update on capecitabine in colorectal cancer. [2015]

4. England 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. [2022]

5. United States 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. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Association of Single-Nucleotide Polymorphisms in Capecitabine Bioactivation Pathway with Adjuvant Therapy Safety in Colorectal Cancer Patients. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel and capecitabine as a first-line combination chemotherapy for advanced gastric cancer. [2022]

8. England 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. [2018]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

A phase II study of capecitabine and docetaxel combination chemotherapy in patients with advanced gastric cancer. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

Antitumor activities of a novel fluoropyrimidine, N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine (capecitabine). [2019]

12. England 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. [2022]