38 Participants Needed

Triple-Drug Combo for Ovarian Cancer

Recruiting at 1 trial location
TO
KD
CM
Overseen ByCallan Myerscough
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

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.

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.12345

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.678910

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.511121314

Research Team

Floor Backes

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.
See 17 more

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.
See 26 more

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 OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Treatment (paclitaxel, lenvatinib, pembrolizumab)Experimental Treatment3 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

Find a Clinic Near You

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

References

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer. [2022]
Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]
Navicixizumab plus Paclitaxel Shows Clinical Benefit in Platinum-Resistant Ovarian Cancer. [2022]
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]
Innovative therapies for advanced ovarian cancer. [2012]
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]
Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. [2023]
Combination lenvatinib plus pembrolizumab in the treatment of ovarian clear cell carcinoma: A case series. [2023]
Phase I evaluation of lenvatinib and weekly paclitaxel in patients with recurrent endometrial, ovarian, fallopian tube, or primary peritoneal Cancer. [2022]
10.United Statespubmed.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]
[New aspects by the therapy of ovarian cancer--What changes after the ASCO-Meeting 2001]. [2008]
The integration of anthracyclines in the treatment of advanced ovarian cancer. [2018]
Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. [2020]
The Gynecologic Oncology Group experience in ovarian cancer. [2022]