Sacituzumab Govitecan for Bile Duct Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Anup K Kasi Loknath Kumar

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Kansas Medical Center

Must not be taking: Corticosteroids, UGT1A1 inhibitors

Disqualifiers: Pregnancy, CNS metastases, Cardiac disease, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well sacituzumab govitecan works in treating patients with cholangiocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced), that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a toxic agent, called SN-38. HRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as TROP2 receptors, and delivers SN-38 to kill them.

Will I have to stop taking my current medications?

The trial requires that you do not use other anti-cancer or investigational drugs while participating. If you are on high-dose corticosteroids or UGT1A1 inhibitors/inducers, you must stop them at least 2 weeks before starting the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is Sacituzumab Govitecan safe for humans?

Sacituzumab Govitecan has been tested in humans with various advanced cancers, and common side effects include nausea, low white blood cell count (neutropenia), diarrhea, tiredness, low red blood cell count (anemia), vomiting, hair loss, constipation, rash, decreased appetite, and abdominal pain. These side effects were observed in more than 25% of patients in clinical trials. ^{1 2 3 4 5}

How is the drug Sacituzumab Govitecan unique for treating bile duct cancer?

Sacituzumab Govitecan is unique because it is an antibody-drug conjugate (ADC) that specifically targets Trop-2, a protein found on many cancer cells, to deliver SN-38, a powerful chemotherapy agent, directly to the tumor. This targeted approach may offer a new option for bile duct cancer, which lacks many standard treatments. ^{2 4 6 7 8}

Eligibility Criteria

This trial is for patients with advanced forms of bile duct cancer, including those whose cancer has spread locally, returned after treatment, or metastasized. Participants must have measurable disease and be able to undergo procedures like biopsies and scans.

Inclusion Criteria

Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN

I agree to use contraception or practice abstinence during and after the study for the specified times.

Exclusion Criteria

I have not had any other cancer besides a low-risk, treated one in the last 3 years.

I have a genetic variation linked to higher risk of side effects from irinotecan.

I am currently using or have used drugs that affect UGT1A1.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sacituzumab govitecan intravenously over 1-3 hours on days 1 and 8 of each 21-day cycle

Up to 2 years

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

24 months

Every 3 months

Treatment Details

Interventions

• Sacituzumab Govitecan (Monoclonal Antibodies)

Trial Overview The trial is testing Sacituzumab Govitecan's effectiveness on cholangiocarcinoma. It involves a monoclonal antibody targeting TROP2 receptors on tumor cells to deliver the toxic agent SN-38 directly to them.

Participant Groups

Group I: Treatment (Sacituzumab govitecan) Experimental Treatment 6 Interventions

Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy, PET/CT or MRI scans, and blood sample collection throughout the study.

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 Nearby Select from list below to view details:

University of Kansas Cancer Center Kansas City, KS

Who Is Running the Clinical Trial?

University of Kansas Medical Center Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

1. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022] On April 22, 2020, the FDA granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY; Immunomedics, Inc.) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Approval was based on data from the IMMU-132-01 trial, a single-arm, multicohort, multicenter, phase I/II trial of sacituzumab govitecan. The assessment of efficacy was based on 108 patients with mTNBC who had previously received at least two prior lines of therapy in the metastatic setting and who received sacituzumab govitecan 10 mg/kg i.v. The assessment of safety was based on 408 patients with advanced solid tumors who had received sacituzumab govitecan at doses up to 10 mg/kg i.v. The primary efficacy endpoint was investigator-assessed objective response rate (ORR) and duration of response (DoR) was a key secondary endpoint. The ORR was 33.3% [36/108; 95% confidence interval (CI), 24.6-43.1], and median DoR among responders was 7.7 months (95% CI, 4.9-10.8). The most common adverse reactions occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. This article summarizes the FDA review process and data supporting the approval of sacituzumab govitecan.

2. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021] To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.

3. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. [2021] Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. A confirmatory phase III trial evaluating sacituzumab govitecan vs. chemotherapy of the provider's choice was published in April 2021. Based on this trial, the FDA granted sacituzumab govitecan full regulatory approval. This antibody-drug conjugate is composed of a monoclonal antibody targeted at Trop-2 and contains the active metabolite of irinotecan, SN-38, as a cytotoxic side moiety. In a phase III clinical trial, sacituzumab govitecan demonstrated a median progression-free survival of 5.7 months vs. 1.7 months with chemotherapy. It is now an additional option for patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

4. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022] Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers.

5. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. [2018] Sacituzumab govitecan (IMMU-132), an antitrophoblastic cell-surface antigen (anti-Trop-2) humanized antibody-SN-38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines the pharmacokinetics and safety of multiple cycles of IMMU-132 at doses of 8 or 10 mg/kg in patients with diverse advanced epithelial cancers.

6. United States pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023] Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC).

7. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021] Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.

8. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. [2023] Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.