Pembrolizumab and Lenvatinib for Platinum- Sensitive Recurrent Ovarian Cancer

NCT04519151 | Recruiting Phase 2

• 1 other identifier: 7405-20
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) for the treatment of platinum sensitive recurrent ovarian cancer. Participants will receive pembrolizumab and lenvatinib.

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Neoplasm of Stomach; Ovarian Diseases; Genital Neoplasms, Female; Ovarian Epithelial Tumor; Urogenital Neoplasms; Neoplasms, Glandular and Epithelial

Keywords

Ovarian Cancer; Platinum sensitive; Ovarian Epithelial; Neoplasms; Genital Neoplasms

Outcome Measures

Primary Outcomes (1)

• PFS of patients treated with pembrolizumab in combination with lenvatinib.

  defined as the time from study treatment initiation to the first documented disease progression according to RECIST 1.1 or death from any cause.

  Up to approximately 27 months

Secondary Outcomes (8)

• Objective response rate (ORR) in patients treated with a combination of pembrolizumab and lenvatinib.

  Up to approximately 27 months

• Time to subsequent therapy (in months)- time from enrollment to next line of therapy initiation

  Up to approximately 27 months

• Overall survival (OS) of the study population.

  Up to approximately 27 months

• Impact of the treatment protocol on health-related quality of life using the QOL questionnaire (EORTC) QLQ-C30

  will be assessed at the pre-treatment visit and at the time of Tumor Imaging (schedualed or unschedualed with a ±3 day window. Additional assessment will be performed and at the end of treatment/discontinuation visit.

• Incidence of treatment-related adverse, serious adverse events, immune-related AEs

  Up to approximately 27 months

Study Arms (1)

Lenvatinib 20 mg + Pembrolizumab 200 mg

EXPERIMENTAL

Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

200 mg administered by IV infusion on Day 1 of each 21-day cycle.

Also known as: KEYTRUDA®, MK-3475

Lenvatinib 20 mg + Pembrolizumab 200 mg

Lenvatinib DRUG

20 mg administered orally (PO) QD during each 21-day cycle.

Also known as: LENVIMA®

Lenvatinib 20 mg + Pembrolizumab 200 mg

Eligibility Criteria

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

You may qualify if:

• Female participants who are at least 18 years of age on the day of signing informed consent, with histologically-confirmed diagnosis of EOC (except from low grade tumors and mucinous histology).
• 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) OR
• A WOCBP who agrees to follow the contraceptive during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease at baseline based on RECIST 1.1. Lesions
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have received a front-line platinum-based regimen per local standard of care or treatment guideline following the primary or interval debunking surgery with radiologically documented disease recurrence no earlier than 6 months following completion of platinum-based therapy.
• Note: Maintenance treatment following front-line treatment is permitted and counted together as part of the front-line treatment. Recurrence is evaluated since last platinum-based chemotherapy administration (for patients treated with maintenance bevacizumab or PARP inhibitors) Note: Patients that received maintenance immune checkpoint inhibitors will be eligible if progression was documented over 6 months since completion of the immunotherapy maintenance treatment.
• Have received 0 to 1 line of chemotherapy for ROC (or 1 to 2 total prior lines counting the front line) and must have a PFI (or treatment-free interval) of \>6 months for each treatment line.
• \. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• \. Have adequately controlled blood pressure (BP) with or without antihypertensive medications 10. Have adequate organ function as defined by blood tests.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test
• The participant is pregnant or breastfeeding at Screening or Baseline, or is expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• The participant has received prior therapy with an anti-PD-1, anti-PD-L1 oranti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) in the last 6 months (6 months are calculated from the last dose until study initiation).
• The participant has received prior systemic anti-cancer therapy mAb, chemotherapy or targeted small molecule therapy within 4 weeks prior to the planned first dose of the study, including investigational agents within 4 weeks. For tyrosine kinase inhibitors (TKIs), other than lenvatinib, and hormonal therapy a shorter interval of 5 half-lives is allowed between prior therapy and study treatment initiation.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• The participant has received prior lenvatinib.
• The participant has received prior radiotherapy within 2 weeks of start of study treatment.
• The patient had prior grade 3 immune related toxicity due to immune checkpoint inhibitors or non-infectious pneumonitis.
• The participant has received more than 2 prior chemotherapy lines.
• The participant has a history of tumor bleeding one month before study enrollment.
• The participant has received a live vaccine within 30 days prior to the first dose of study drug.
• The participant 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.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• The participant 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.
• Note: The use of physiologic doses of corticosteroids is allowed.

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba Medical center

Ramat Gan, Israel

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Stomach Neoplasms; Ovarian Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Male Urogenital Diseases

Study Officials

• Ronnie Shapira, MD

  Ronnie.Shapira@sheba.health.gov.il

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ronnie Shapira, MD

CONTACT

+972-526666708; Ronnie.Shapira@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Lable
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D, Head onco-gynecological service, Principal Investigator

Model Details: single arm

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 19, 2020
• Study Start: April 12, 2021
• Primary Completion: November 1, 2023
• Study Completion (Estimated): November 1, 2029
• Last Updated: June 8, 2023

Record last verified: 2023-06

Locations

IL (1)