Lenvatinib, Pembrolizumab, and Paclitaxel for Treatment of Recurrent Endometrial, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT04781088 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-20172NCI-2021-01256
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Platinum-Resistant Ovarian Carcinoma; Platinum-Resistant Primary Peritoneal Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Platinum-Resistant Fallopian Tube Carcinoma

Keywords

endometrial cancer; ovarian cancer; platinum resistant; phase 2

Outcome Measures

Primary Outcomes (1)

• Objective tumor response

  Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Will be reported as a percentage and will be calculated by the number of patients with a complete or partial response divided by the total number of patients. The percentage of patients with stable disease and progressive disease will be calculated in a similar fashion.

  through study completion, an average of 1 year

Secondary Outcomes (2)

• Safety and Toxicity

  through study completion, an average of 1 year

• Progression free survival

  through study completion, an average of 1 year

Study Arms (1)

Treatment (paclitaxel, lenvatinib, pembrolizumab)

EXPERIMENTAL

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.

Drug: Lenvatinib; Drug: Paclitaxel; Biological: Pembrolizumab

Interventions

Lenvatinib DRUG

Given PO

Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Treatment (paclitaxel, lenvatinib, pembrolizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (paclitaxel, lenvatinib, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (paclitaxel, lenvatinib, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who are at least 18 years of age on the day of signing informed consent will be enrolled in this study
• Women with histologically confirmed endometrial cancer, epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer (all histological subtypes)
• Patients must have received prior treatment with a platinum containing regimen and may have received 1-3 prior regimens. Hormonal therapy and maintenance therapy (with bevacizumab or PARP inhibitor) does not count towards the number of prior treatments
• Patients with ovarian, fallopian tube or primary peritoneal cancer must be platinum resistant (progression \< 6 months after completion of a platinum containing regimen) or not a candidate for further platinum treatment
• Patients with and without mismatch repair deficiency are allowed
• Prior PD-1/PD-L1 inhibitors are allowed as long as this was not the most recent regimen and treatment was not discontinued due to side effects/toxicity. Prior weekly paclitaxel is allowed as long as this was not the most recent regimen and treatment was not discontinued due to side effects/toxicity
• Prior targeted therapy targeting angiogenesis is allowed as long as treatment was not discontinued due to side effects/toxicity
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 months (corresponding to time needed to eliminate any study treatment\[s\] MK and or any active comparator/combination) plus 30 days (a menstruation cycle) after the last dose of study treatment
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Absolute neutrophil count (ANC) \>= 1500/uL (within 10 days prior to the start of study treatment)

You may not qualify if:

• A women of child birth potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to registration.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives whichever is shorter prior to study entry. Patients may not have received biologics, targeted therapy or immunotherapy for 4 weeks (6 weeks for nitrosoureas or mitomycin C). Hormonal therapy is not considered anti-neoplastic therapy.
• Has received prior radiotherapy within 3 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• Has received a live vaccine within 30 days prior to the first dose of study drug. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab, lenvatinib, or paclitaxel and/or any of its excipients. Note, patients with paclitaxel hypersensitivity are eligible if the if infusion can safely be completed with reduced infusion rates and premedication
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required unless the patient is at risk for, or has symptoms or signs of, hepatitis
• Has a known history of active TB (Bacillus Tuberculosis)
• Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab, lenvatinib and paclitaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Significant cardiovascular disease

Sponsors & Collaborators

• Floor Backes, MD: lead

Study Sites (2)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Endometrial Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

lenvatinib; Paclitaxel; Taxes; pembrolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Fallopian Tube Diseases; Adnexal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Floor Backes, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: March 4, 2021
• Study Start: September 1, 2021
• Primary Completion: July 1, 2025
• Study Completion (Estimated): August 31, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)