Triple-Drug Combo for Ovarian Cancer

Recruiting at 1 trial location

Overseen By Callan Myerscough

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Floor Backes, MD

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Active CNS metastases, Severe hypersensitivity, Autoimmune disease, Hepatitis, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

38 Participants Needed

Trial Summary

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. However, you cannot have received certain cancer treatments or investigational drugs within a specific time frame before starting the trial. It's best to discuss your current medications with the trial team to understand any potential interactions.

What data supports the effectiveness of the drug combination Lenvatinib, Paclitaxel, and Pembrolizumab for ovarian cancer?

Research shows that paclitaxel, when combined with other drugs like navicixizumab, has shown benefits in treating platinum-resistant ovarian cancer. Additionally, pembrolizumab has been evaluated in combination with other drugs for similar conditions, suggesting potential effectiveness in combination therapies. ^{1 2 3 4 5}

What safety data exists for the triple-drug combo treatment for ovarian cancer?

The combination of lenvatinib and pembrolizumab has shown a safety profile with common side effects like high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss. Lenvatinib and paclitaxel together have been studied for ovarian cancer, focusing on finding the right dose and understanding side effects. ^{6 7 8 9 10}

What makes the triple-drug combo for ovarian cancer unique?

The triple-drug combo for ovarian cancer is unique because it combines Lenvatinib, Paclitaxel, and Pembrolizumab, which includes an antiangiogenic agent (Lenvatinib) and an immune checkpoint inhibitor (Pembrolizumab), potentially offering a novel approach by targeting both tumor blood supply and the immune system, unlike the standard platinum-taxane combinations. ^{5 11 12 13 14}

What is the purpose of this trial?

This phase II clinical trial studies the effect of lenvatinib, pembrolizumab, and paclitaxel in treating patients with endometrial, epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent). While all 3 study drugs are FDA approved, and 2-drug combinations have been studied, the 3- drug combination has not been studied yet. The investigators believe that the addition of pembrolizumab to weekly paclitaxel and lenvatinib (or weekly paclitaxel to pembrolizumab and lenvatinib) is highly effective and safe with manageable side effects in both recurrent endometrial and platinum resistant ovarian cancer. The purpose of this trial is to study how well lenvatinib, pembrolizumab, and weekly paclitaxel work together in women who have recurrent endometrial cancer and/or recurrent platinum resistant ovarian, fallopian tube, and primary peritoneal cancer, and what kind of side effects patients may experience.

Research Team

Floor Backes, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for women at least 18 years old with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer who have had platinum-based treatment. They must not be pregnant or breastfeeding and should have an acceptable organ function. Prior treatments are allowed under certain conditions but no recent severe side effects from similar drugs.

Inclusion Criteria

My ovarian, fallopian tube, or peritoneal cancer is resistant to platinum-based treatments.

Your hemoglobin level is at least 9.0 g/dL or 5.6 mmol/L within the last 10 days before starting the study treatment.

Your kidney function should be measured according to the hospital's usual method.

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I have had a bowel blockage or currently have a partial blockage or a PEG-tube.

I have had pneumonitis treated with steroids or have it now.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib, pembrolizumab, and paclitaxel. Lenvatinib is taken orally daily, pembrolizumab is administered intravenously on day 1, and paclitaxel is administered intravenously on days 1, 8, and 15 of a 21-day cycle.

Up to 2 years

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Lenvatinib
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests a combination of three FDA-approved drugs: Lenvatinib, Pembrolizumab, and Paclitaxel in patients with specific recurrent cancers. The goal is to determine the effectiveness and safety of this triple-drug regimen which has not been studied before.

Participant Groups

Group I: Treatment (paclitaxel, lenvatinib, pembrolizumab) Experimental Treatment 3 Interventions

Patients receive paclitaxel IV over 1 hour on days -15 and -8 and lenvatinib PO QD on days -15 to 0. Beginning cycle 1 day 1, patients receive lenvatinib PO QD, pembrolizumab IV over 30 minutes on day 1, and paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles with pembrolizumab repeats every 3 weeks for up to 2 years, and cycles with paclitaxel and lenvatinib repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

Floor Backes, MD

Lead Sponsor

Trials

2

Recruited

40+

Floor Backes

Lead Sponsor

Trials

3

Recruited

70+

Findings from Research

In a phase Ib study involving 44 patients with platinum-resistant ovarian cancer, the combination of navicixizumab and paclitaxel showed a promising overall objective response rate of 43.2%, indicating its potential efficacy in treating this difficult-to-treat cancer.

The treatment was well-tolerated, with no dose-limiting toxicities reported, although some patients experienced manageable side effects like hypertension and neutropenia, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. Fu, S., Corr, BR., Culm-Merdek, K., et al.[2022]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

The combination of navicixizumab and paclitaxel demonstrated lasting effectiveness in treating patients with platinum-resistant ovarian cancer, indicating a potential new treatment strategy.

This finding suggests that navicixizumab may enhance the therapeutic impact of paclitaxel in a challenging patient population, although specific details on the number of subjects and study duration were not provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navicixizumab plus Paclitaxel Shows Clinical Benefit in Platinum-Resistant Ovarian Cancer. [2022]

Research is focusing on non-cross-resistant drugs like oxaliplatin and topotecan for treating drug-resistant ovarian cancer, with many being tested in combination therapies to improve outcomes.

Innovative strategies such as anticancer vaccines and gene therapy are being explored, highlighting the importance of clinical trials for women with advanced ovarian cancer due to low current cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative therapies for advanced ovarian cancer. Trimble, EL.[2012]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

In a small case series of three patients with recurrent ovarian clear cell carcinoma (OCCC), the combination of lenvatinib and pembrolizumab resulted in a remarkable overall response rate of 100%.

Patients experienced progression-free survival ranging from 10 months to not-yet-reached, indicating that this treatment may be effective for those with platinum-resistant disease, although two patients ultimately succumbed to their illness after 14 and 27 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. Calo, CA., Levine, MD., Brown, MD., et al.[2023]

Docetaxel has shown comparable effectiveness to paclitaxel when combined with carboplatin for treating advanced ovarian cancer, with a potentially better safety profile.

Current treatments for platinum-resistant ovarian cancer are limited, and while some experimental therapies targeting the epidermal growth factor receptor show promise, more research is needed to find effective new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. Costa, SD., von Minckwitz, G., Wernicke, K., et al.[2008]

The combination of platinum and paclitaxel has been established as the standard treatment for advanced ovarian cancer since the late 1990s, with further studies suggesting that adding noncross-resistant drugs like epirubicin may enhance treatment efficacy.

In a phase III trial involving 1281 patients, 87% completed six cycles of treatment, providing valuable data on treatment response and toxicity, which will help assess the effectiveness of the new combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of anthracyclines in the treatment of advanced ovarian cancer. Lück, HJ., Du Bois, A., Weber, B., et al.[2018]

A platinum/taxane combination is identified as the optimal treatment backbone for chemonaive ovarian cancer based on trials from the Gynecologic Oncology Group over the past 15 years.

Adding a third drug to this combination is unlikely to significantly improve outcomes; however, using sequential doublets of drugs like cisplatin with gemcitabine or topotecan with doxil or etoposide may enhance treatment efficacy due to their complementary mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Gynecologic Oncology Group experience in ovarian cancer. McGuire, WP., Brady, MF., Ozols, RF.[2022]

References

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

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. [2022]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

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

Navicixizumab plus Paclitaxel Shows Clinical Benefit in Platinum-Resistant Ovarian Cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A phase 1b, open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery. [2015]

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

Innovative therapies for advanced ovarian cancer. [2012]

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

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

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

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. [2023]

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

Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal Cancer. [2022]

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

A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]

12. England pubmed.ncbi.nlm.nih.gov

The integration of anthracyclines in the treatment of advanced ovarian cancer. [2018]

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

Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. [2020]

14. England pubmed.ncbi.nlm.nih.gov

The Gynecologic Oncology Group experience in ovarian cancer. [2022]