Sacituzumab + Cisplatin for Ovarian and Uterine Cancer

Overseen By Melanie Kier, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Investigational agents, Chemotherapy

Disqualifiers: Severe diseases, CNS metastases, others

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

Compensation: Varies

Number of Visits: 42

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, Phase 1 study with a dose expansion cohort of Sacituzumab Govitecan in Combination with Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer. The goal of the study is to determine the optimal dose of sacituzumab govitecan for use in combination with cisplatin for treatment of epithelial ovarian and endometrial cancers.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that ongoing therapy with any prohibited medications is not allowed. It's best to discuss your current medications with the trial team to see if they are compatible with the study requirements.

What data supports the effectiveness of the drug combination Sacituzumab and Cisplatin for ovarian and uterine cancer?

Cisplatin, a component of the treatment, has shown effectiveness in combination with other drugs like paclitaxel for improving survival rates in advanced ovarian cancer. Additionally, antibody-drug conjugates, like Sacituzumab, have shown promise in treating some cancers, suggesting potential benefits when combined with Cisplatin. ^{1 2 3 4 5}

What safety data exists for Sacituzumab and Cisplatin in humans?

Cisplatin, also known as CDDP, has been used in various cancer treatments and is known to cause side effects like nausea, vomiting, and blood-related issues such as neutropenia (low white blood cell count) and thrombocytopenia (low platelet count). It can also cause kidney problems and hearing loss. Sacituzumab, marketed as Trodelvy, is generally used for breast cancer, but specific safety data for its combination with Cisplatin in ovarian and uterine cancer is not provided in the available research. ^{6 7 8 9 10}

How is the drug Sacituzumab + Cisplatin different from other treatments for ovarian and uterine cancer?

Sacituzumab govitecan is unique because it is an antibody-drug conjugate (a targeted therapy that combines an antibody with a drug) that specifically targets the Trop-2 protein on cancer cells, delivering the chemotherapy drug SN-38 directly to them. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{11 12 13 14 15}

Research Team

Amy D. Tiersten

Principal Investigator

Icahn School of Medicine at Mount Sinai Division of Hematology and Medical Oncology

Eligibility Criteria

This trial is for women aged 18+ with recurrent ovarian or endometrial cancer that's sensitive to platinum-based chemo, showing progression more than 6 months after the last dose. Participants must have a WHO performance status of 0-1 and measurable disease. They should not have severe diseases, be pregnant/nursing, or have had certain treatments recently.

Inclusion Criteria

My ovarian or endometrial cancer has returned but responded well to the last platinum-based treatment.

I have at least one cancer lesion that can be measured on a CT scan.

My cancer is confirmed to be ovarian or endometrial.

Exclusion Criteria

Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

I agree to use effective birth control during the study and for 4 weeks after.

I haven't taken any experimental drugs in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Safety run-in phase utilizing a 3+3 design with dose de-escalation if toxicity is observed

3-6 weeks

Visits every 21 days

Dose Expansion Cohort

Evaluate the preliminary efficacy and tolerability of the experimental regimen

6 months

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cisplatin
• Sacituzumab

Trial Overview The study tests Sacituzumab Govitecan combined with Cisplatin in patients with specific types of ovarian and endometrial cancers. It aims to find the best dose for this combination therapy in an open-label, Phase 1 trial setting.

Participant Groups

Group I: Ovarian cancer Cohort Experimental Treatment 2 Interventions

DEC 3+3 dose expansion of Sacituzumab Govitecan in Combination with Cisplatin

Group II: Endometrial cancer Cohort Experimental Treatment 2 Interventions

DEC 3+3 dose expansion of Sacituzumab Govitecan in Combination with Cisplatin

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

Two large randomized clinical trials demonstrated that a chemotherapy regimen combining cisplatin and paclitaxel significantly improves clinical response rates, progression-free survival, and overall survival in women with advanced epithelial ovarian cancer compared to cisplatin and cyclophosphamide.

With a median follow-up of 6.5 years, the studies showed an 11% absolute increase in survival for patients receiving the cisplatin-paclitaxel regimen, confirming its effectiveness as a frontline treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. Piccart, MJ., Bertelsen, K., Stuart, G., et al.[2022]

A randomized trial involving women with advanced ovarian cancer found that the chemotherapy combination of cisplatin and paclitaxel resulted in a higher objective response rate and improved progression-free and overall survival compared to cisplatin and cyclophosphamide.

Future research will likely aim to enhance the delivery of this effective combination and explore the addition of other active agents to further improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status and future directions of platinum/paclitaxel-based chemotherapy of ovarian cancer. Markman, M.[2015]

The standard treatment for platinum-resistant ovarian cancer involves non-platinum chemotherapy, with weekly paclitaxel showing the greatest benefits, but overall response rates remain modest, highlighting the need for improved therapies.

Recent trials indicate that while combination treatments with antiangiogenics have improved outcomes, there is still a lack of reliable biomarkers to predict treatment response, emphasizing the importance of thoughtful clinical trial designs and the exploration of novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Eskander, RN., Moore, KN., Monk, BJ., et al.[2023]

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

In a phase II trial involving 20 patients with advanced ovarian or primary peritoneal cancer resistant to platinum and paclitaxel, the combination of topotecan and cisplatin showed a low clinical response rate of only 13.3%, indicating minimal efficacy for this treatment approach.

The treatment was associated with significant toxicity, including a 50% rate of severe thrombocytopenia and 30% rate of severe neutropenia, leading to dose reductions in 45% of patients and one septic death, highlighting safety concerns with this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of salvage chemotherapy with topotecan and cisplatin in patients with paclitaxel- and platinum-resistant recurrent ovarian or primary peritoneal cancer: a phase II pilot study. Ghamande, SA., Piver, MS.[2019]

The combination of paclitaxel and carboplatin is currently the preferred first-line treatment for advanced ovarian cancer, showing less toxicity and similar efficacy compared to paclitaxel and cisplatin, based on evidence from large randomized trials involving multiple patients.

Weekly paclitaxel administration has a more favorable toxicity profile than higher dosed three-weekly schedules, resulting in reduced side effects like neutropenia and neurotoxicity, which is crucial for improving patient quality of life during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of paclitaxel and new platinum compounds in the treatment of advanced ovarian cancer. Vermorken, JB.[2019]

In a trial involving 22 breast cancer patients, the combination of paclitaxel and cisplatin was well tolerated, with a high overall response rate of 94%, including complete and partial responses.

Dose-limiting neutropenia was observed at the starting dose of paclitaxel (90 mg/m2), preventing dose escalation, but the regimen showed minimal severe nonhematologic toxicity, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly paclitaxel (Taxol) and cisplatin in breast and ovarian cancer. Gelmon, KA.[2015]

In a study of 115 patients with clear cell adenocarcinoma of the ovary and recurrent ovarian carcinoma, the combination therapy of nedaplatin and irinotecan (NDP/CPT) showed similar efficacy to cisplatin and irinotecan (CDDP/CPT) in terms of overall survival and progression-free survival, particularly in early-stage patients.

NDP/CPT was associated with significantly lower rates of severe hematological and non-hematological toxicities compared to CDDP/CPT, indicating that NDP/CPT is a safer treatment option with milder side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nedaplatin and irinotecan combination therapy is equally effective and less toxic than cisplatin and irinotecan for patients with primary clear cell adenocarcinoma of the ovary and recurrent ovarian carcinoma. Machida, S., Sato, T., Fujiwara, H., et al.[2021]

In a phase I dose-escalation study involving 6 patients with advanced cervical and ovarian cancers, the maximum tolerated dose (MTD) for nedaplatin was determined to be 80 mg/m2, while for cisplatin it was 60 mg/m2, with hematotoxicity identified as the main dose-limiting toxicity (DLT).

The combination therapy resulted in severe neutropenia in all patients at the highest doses, along with mild side effects like nausea and slight hearing loss, suggesting that while the treatment is effective, careful monitoring of blood cell counts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a combination chemotherapy of nedaplatin and cisplatin]. Nishida, M., Satoh, Y., Nishide, K., et al.[2013]

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., et al.[2022]

Trop-2 was found to be expressed in 95.1% of uterine serous carcinoma (USC) samples, indicating that targeting this protein with sacituzumab govitecan (SG) could be a promising treatment strategy for most USC patients.

In preclinical studies, SG demonstrated significant anti-tumor activity against Trop-2 positive USC cell lines and xenografts, leading to growth inhibition and increased survival in treated mice, suggesting its potential efficacy in advanced or recurrent USC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Han, C., Perrone, E., Zeybek, B., et al.[2020]

Sacituzumab-govitecan (SG) demonstrated significant antitumor activity in carcinosarcoma (CS) models, particularly in tumors expressing the Trop-2 marker, with a notable improvement in overall survival at 90 days compared to control groups.

In vitro studies showed that Trop-2 positive cell lines were more sensitive to SG, indicating that Trop-2 expression could be a key factor in determining the efficacy of this treatment for patients with carcinosarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Lopez, S., Perrone, E., Bellone, S., et al.[2022]

Sacituzumab govitecan (SG) showed promising efficacy in treating advanced epithelial cancers, with partial response rates of 22.2% in endometrial cancer and 17.7% in small-cell lung cancer, indicating its potential as a treatment option.

The safety profile of SG was consistent with previous studies, with common treatment-related adverse events including neutropenia (57.8%) and nausea (62.6%), and a notable incidence of grade ≥3 neutropenia in patients with specific genetic variations (UGT1A1∗28 homozygotes).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Bardia, A., Messersmith, WA., Kio, EA., et al.[2021]

In a phase II study involving 113 patients with metastatic urothelial carcinoma who had previously progressed on platinum-based chemotherapy and checkpoint inhibitors, sacituzumab govitecan (SG) demonstrated an objective response rate of 27%, indicating significant efficacy in this difficult-to-treat population.

SG was associated with a manageable safety profile, with the most common severe side effects being neutropenia (35%) and diarrhea (10%), leading to a 6% discontinuation rate due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. Tagawa, ST., Balar, AV., Petrylak, DP., et al.[2022]

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer. [2022]

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

Current status and future directions of platinum/paclitaxel-based chemotherapy of ovarian cancer. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. [2023]

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

Treatment of refractory and recurrent ovarian cancer. [2005]

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

Role of salvage chemotherapy with topotecan and cisplatin in patients with paclitaxel- and platinum-resistant recurrent ovarian or primary peritoneal cancer: a phase II pilot study. [2019]

6. England pubmed.ncbi.nlm.nih.gov

The integration of paclitaxel and new platinum compounds in the treatment of advanced ovarian cancer. [2019]

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

Biweekly paclitaxel (Taxol) and cisplatin in breast and ovarian cancer. [2015]

8. Greece pubmed.ncbi.nlm.nih.gov

Nedaplatin and irinotecan combination therapy is equally effective and less toxic than cisplatin and irinotecan for patients with primary clear cell adenocarcinoma of the ovary and recurrent ovarian carcinoma. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study of a combination chemotherapy of nedaplatin and cisplatin]. [2013]

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

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022]

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

In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. [2020]

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

Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. [2021]

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

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. [2022]

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

Treatment of ovarian cancer: current status. [2015]