Sacituzumab Govitecan in Combination With Capecitabine for Advanced Gastrointestinal Cancers After Progression on Standard Therapy

NCT06065371 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HFH-23-03
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastrointestinal Cancer

Keywords

pancreatic cancer; biliary tract cancers; colorectal cancer; esophageal cancer; gastroesophageal cancer; gastric cancer

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint

  Recommended phase 2 dose (RP2D)

  18 months

Secondary Outcomes (5)

• Adverse Events (AEs)

  Through study completion, an average of 18 months

• Objective response rate (ORR)

  Through study completion, an average of 18 months

• Duration of Response (DoR)

  18 months

• Progression-free Survival (PFS)

  18 months

• Overall Survival (OS)

  18 months

Other Outcomes (1)

• Exploratory Endpoint

  18 months

Study Arms (1)

Sacituzumab govitecan and capecitabine

EXPERIMENTAL

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.

Drug: Capecitabine; Drug: Sacituzumab govetican

Interventions

Capecitabine DRUG

Capecitabine is a fluoropyrimidine that is metabolized to 5-fluorouracil, which inhibits thymidylate synthase. Capecitabine is available in white or off-white tablets with doses of 500mg and 150mg doses. 500mg dose tablets will be used on this trial. Capecitabine will be ordered as a standard of care and provided commercially.

Also known as: Xeloda

Sacituzumab govitecan and capecitabine

Sacituzumab govetican DRUG

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2-expressing cells and is covalently attached to the topoisomerase I inhibitor SN-38. Sacituzumab govitecan will be provided by Gilead Sciences. Sacituzumab govitecan for injection, 180 mg and 200 mg, is available as a powder that is to be reconstituted with 20 mL of 0.9% Sodium Chloride Injection prior to intravenous infusion. Following reconstitution, each single-dose vial of Sacituzumab govitecan results in a concentration of 10mg/mL with pH of 6.5.

Also known as: Trodelvy

Sacituzumab govitecan and capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients, 18 years of age or older, able to understand and give written informed consent
• Patients with the histologically or cytologically documented metastatic adenocarcinoma of gastrointestinal origin, including gastroesophageal, colorectal, and pancreaticobiliary that have failed standard therapy
• Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm3, and platelets ≥ 100,000/μL).
• Adequate hepatic function (bilirubin ≤ 1.5x upper limit normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN or ≤ 5xULN if known liver metastases, and serum albumin \> 3 g/dL).
• Adequate renal function (Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation.
• Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (total abstinence \[if it is her preferred and usual lifestyle\], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 6 months after study drug discontinuation. For sites outside of the European Union (EU), it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the subject, then the subject must agree to use a medically acceptable method of contraception, ie, double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide. If currently abstinent, the subject must agree to use a highly effective method as described above if she becomes sexually active during the study period or for 6 months after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 28 days before dosing and must continue to use the same contraceptive during the study and for 6 months after study drug discontinuation.
• Willing and able to comply with the requirements and restrictions in this protocol

You may not qualify if:

• Positive serum pregnancy test or women who are breastfeeding.
• Known hypersensitivity to the study drug(s), its metabolites, or formulation excipient.
• Requirement for ongoing therapy with or prior use of any prohibited medications listed in protocol.
• Have had a prior anticancer biologic agent within 4 weeks prior to enrolment or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (i.e., ≥ Grade 2 is considered not recovered) from adverse events (AEs) at the time of study entry. Note: patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study. Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Have previously received topoisomerase 1 inhibitors.
• Have an active second malignancy. Note: patients with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to enrolment, or patients with surgically cured tumors with low risk of recurrence (e.g., nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll.
• Have unstable brain metastases. Note: Patients with stable brain metastasis can be included. "Stable" brain metastases may be defined as: Prior local treatment by radiation, surgery, or stereotactic surgery, imaging - stable or decreasing size after such local treatment, clinically stable signs and symptoms for at least 4 weeks, ≥2 weeks from discontinuation of anti-seizure medication. Patient may receive low and stable doses of corticosteroids ≤ 20 mg prednisone or equivalent daily. It should be confirmed by MRI/CT scan that patient has had stable brain metastasis for 4 weeks prior to treatment.
• Met any of the following criteria for cardiac disease:
• Myocardial infarction or unstable angina pectoris within 6 months of enrolment.
• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
• New York Heart Association (NYHA) class III or greater congestive heart failure or left ventricular ejection fraction of \< 40%.
• Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrolment.
• Have active serious infection requiring antibiotics.
• Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at screening) with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded.

Sponsors & Collaborators

• Henry Ford Health System: lead
• Gilead Sciences: collaborator

Study Sites (1)

Henry Ford Cancer-Detroit

Detroit, Michigan, 48201, United States

RECRUITING

Related Publications (7)

• Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155.

  PMID: 24840647 BACKGROUND

• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.

  PMID: 36633525 BACKGROUND

• Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, Thomas SS, Govindan SV, Maliakal PP, Wegener WA, Hamburger SA, Sharkey RM, Goldenberg DM. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res. 2015 Sep 1;21(17):3870-8. doi: 10.1158/1078-0432.CCR-14-3321. Epub 2015 May 5.

  PMID: 25944802 BACKGROUND

• Fong D, Moser P, Krammel C, Gostner JM, Margreiter R, Mitterer M, Gastl G, Spizzo G. High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer. 2008 Oct 21;99(8):1290-5. doi: 10.1038/sj.bjc.6604677. Epub 2008 Sep 23.

  PMID: 18813308 BACKGROUND

• Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M. Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res. 2006 May 15;12(10):3057-63. doi: 10.1158/1078-0432.CCR-05-1961.

  PMID: 16707602 BACKGROUND

• Zhao W, Zhu H, Zhang S, Yong H, Wang W, Zhou Y, Wang B, Wen J, Qiu Z, Ding G, Feng Z, Zhu J. Trop2 is overexpressed in gastric cancer and predicts poor prognosis. Oncotarget. 2016 Feb 2;7(5):6136-45. doi: 10.18632/oncotarget.6733.

  PMID: 26716416 BACKGROUND

• Bardia A, Tolaney SM, Punie K, Loirat D, Oliveira M, Kalinsky K, Zelnak A, Aftimos P, Dalenc F, Sardesai S, Hamilton E, Sharma P, Recalde S, Gil EC, Traina T, O'Shaughnessy J, Cortes J, Tsai M, Vahdat L, Dieras V, Carey LA, Rugo HS, Goldenberg DM, Hong Q, Olivo M, Itri LM, Hurvitz SA. Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Ann Oncol. 2021 Sep;32(9):1148-1156. doi: 10.1016/j.annonc.2021.06.002. Epub 2021 Jun 8.

  PMID: 34116144 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Pancreatic Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms

Interventions

Capecitabine; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Biliary Tract Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Maria Diab, MD

CONTACT

313-920-4051; mdiab2@hfhs.org

Meghan Gauronskas, RN

CONTACT

313-693-5904; mgauron1@hfhs.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 3+3

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: October 3, 2023
• Study Start: November 20, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)