Pembrolizumab/placebo plus paclitaxel with or without bevacizumab for platinum-resistant recurrent ovarian cancer

JRCT ID: jRCT2051210184

Registered date:02/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Platinum-resistant Recurrent Ovarian Cancer
• Date of first enrollment: 01/04/2022
• Target sample size: 40
• Countries of recruitment: USA,Japan,Belgium,Japan,Denmark,Japan,Finland,Japan,France,Japan,Germany,Japan,Italy,Japan,Netherlands,Japan,Norway,Japan,United Kingdom,Japan,Ireland,Japan,Israel,Japan,Turkey,Japan,Poland,Japan,Australia,Japan,New Zealand,Japan,Korea,Japan,China,Japan,Russia,Japan,Brazil,Japan,Chile,Japan,Colombia,Japan,Mexico,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

- Participants receive pembrolizumab 400 mg or placebo via IV infusion on Day 1 of each 6-week cycle (Q6W) for up to 18 cycles (up to approximately 2 years).

- Participants receive paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle.
Participants who experience a severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel 70 mg/m^2 in place of paclitaxel on Day 1 Q3W after Sponsor consultation.

- Participants may also receive bevacizumab 15 mg/kg via IV infusion of each 3-week cycle

Outcome(s)

• Primary Outcome: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator

Secondary Outcome

1. Overall survival (OS)
2. PFS per RECIST 1.1 by Blinded Independent Central Review (BICR)
3. Number of Participants who Experience an Adverse Event (AE)
4. Number of Participants who Discontinue Study Treatment due to an AE
5. Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
6. Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30
7. Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale
8. TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

- Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
- Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy or bevacizumab; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
- Has provided documented informed consent for the study.
- Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
- Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
- For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of <1% per year).
- Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator.
- Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
- Have adequate organ function.

Exclude criteria

- Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
- Has primary platinum-refractory disease, defined as disease that has progressed per RECIST 1.1 while receiving first-line platinum-based therapy.
- Has prior disease progression on weekly paclitaxel alone.
- Has uncontrolled hypertension.
- Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
- Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
- Has received >2 prior lines of systemic therapy for OC.
- Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
- Has received prior radiation therapy within 2 weeks of start of study intervention.
- Has not recovered adequately from surgery and/or any complications from the surgery.
- Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has severe hypersensitivity (>=Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of Hepatitis B or known active Hepatitis C virus infection.
- Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
- Has had an allogenic tissue/solid organ transplant.

Related Information

• Primary Sponsor: Hoki Toshifumi
• Secondary ID(s): NCT05116189