Sacituzumab Govitecan for Bile Duct Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Corticosteroids, UGT1A1 inhibitors

Disqualifiers: Pregnancy, CNS metastases, Cardiac disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 5

Duration: Up to 2 years

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called sacituzumab govitecan for individuals with bile duct cancer that is locally advanced, recurrent, or metastatic. The treatment employs a monoclonal antibody to target and deliver a toxic agent directly to cancer cells, aiming for more effective cell destruction. It is intended for those whose cancer has progressed despite previous treatment. Individuals with cholangiocarcinoma that has returned or spread and who have tried at least one other treatment may find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that sacituzumab govitecan is likely to be safe for humans?

Research has shown that sacituzumab govitecan has undergone testing in various studies for safety and effectiveness. Most patients in these studies tolerated sacituzumab govitecan well. Common side effects include nausea, tiredness, and low blood cell counts, which standard care can usually manage.

This drug is a targeted therapy, delivering a toxic agent directly to cancer cells, which may cause specific side effects. However, these side effects are often less severe than those from traditional chemotherapy. The FDA has also approved sacituzumab govitecan for other cancers, such as triple-negative breast cancer, indicating a well-understood safety profile. Always consult a healthcare provider for personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sacituzumab govitecan is unique because it combines an antibody with a chemotherapy drug to specifically target and kill cancer cells in bile duct cancer. Unlike traditional treatments like surgery, radiation, and systemic chemotherapy, sacituzumab govitecan delivers chemotherapy directly to the cancer cells, potentially reducing side effects on healthy cells. Researchers are excited about this treatment because it offers a targeted approach that might be more effective and less toxic than current options.

What evidence suggests that sacituzumab govitecan might be an effective treatment for bile duct cancer?

Research has shown that sacituzumab govitecan, the investigational treatment in this trial, yields promising results in fighting cancer. In earlier studies, about one-third of patients who received this drug experienced a reduction or halt in cancer growth. This drug targets a protein called Trop-2 on cancer cells and delivers a toxic substance to kill them. Sacituzumab govitecan has proven effective in treating other types of cancer, offering hope for bile duct cancer treatment. Overall, the drug has demonstrated its ability to shrink tumors and is generally safe in various trials. ^{1 2 3 4 5}

Who Is on the Research Team?

Anup K Kasi Loknath Kumar

Principal Investigator

University of Kansas

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Sacituzumab Govitecan

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Sacituzumab govitecan (SG) demonstrated effectiveness in treating relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC), with a median overall survival of 12.9 months and an objective response rate of 34% based on an analysis of 412 patients across three trials.

The treatment was associated with significant adverse effects, particularly myelosuppression, with 46% of patients experiencing grade ≥3 neutropenia, and there were four treatment-related deaths reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. Cheng, SX., Chen, QC., Lin, GH., et al.[2023]

Sacituzumab govitecan-hziy (TRODELVY) received accelerated FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on a trial involving 108 patients, showing an objective response rate of 33.3% and a median duration of response of 7.7 months.

The safety profile was assessed in a larger group of 408 patients, with common side effects including nausea, neutropenia, and fatigue, occurring in 25% or more of patients, indicating that while effective, the treatment can have significant adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Wahby, S., Fashoyin-Aje, L., Osgood, CL., et al.[2022]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

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. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

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. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) in patients with endocrine-resistant HR+/HER2- metastatic breast cancer, showing a 34% reduction in the risk of progression or death compared to standard chemotherapy.

The safety profile of SG was manageable, with notable grade ≥ 3 adverse events including neutropenia and diarrhea, but it still represents a promising treatment option for patients with limited alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. Rugo, HS., Bardia, A., Marmé, F., et al.[2023]

Sacituzumab govitecan received full FDA approval after a phase III trial showed it significantly improves progression-free survival in patients with metastatic triple-negative breast cancer, achieving a median of 5.7 months compared to just 1.7 months with standard chemotherapy.

This treatment is an antibody-drug conjugate that targets the Trop-2 receptor and delivers the active metabolite of irinotecan, SN-38, directly to cancer cells, making it a promising option for patients who have already undergone at least two prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. Fleming, PJ., Karpio, S., Lombardo, N.[2021]

Citations

1. aacrjournals.org aacrjournals.org/mct/article/24/11/1775/766871/The-Antibody-Drug-Conjugate-Sacituzumab-Govitecan

The Antibody–Drug Conjugate Sacituzumab Govitecan (IMMU ... Several clinical trials targeting HER2 in biliary tract cancer have shown promising results (31–33). Notably, the HERB trial (33), a phase II ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1814213

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple ... In conclusion, sacituzumab govitecan-hziy (IMMU-132) had efficacy with a 33% response rate in a heavily pretreated population of patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01631552

Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults ... The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33741442/

Sacituzumab govitecan, a Trop-2-directed antibody-drug ... Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0923753421008838

Sacituzumab govitecan, a Trop-2-directed antibody-drug ... This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously ...