Pembrolizumab/placebo plus paclitaxel with or without bevacizumab for platinum-resistant recurrent ovarian cancer.
- Conditions
- Platinum-resistant Recurrent Ovarian CancerMedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-005027-37-PL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 616
A participant will be eligible for inclusion in the study if the participant meets the following criteria:
1. Has histologically confirmed epithelial (including high-grade serous or predominantly serous, low-grade serous, any-grade endometrioid, malignant mixed Müllerian tumors [carcinosarcoma], or clear cell) ovarian, fallopian tube, or primary peritoneal carcinoma.
2. Has received 1 or 2 prior lines of systemic therapy for OC, including at least 1 prior platinum-based therapy.
– Participants must have received at least 4 cycles but not more than 9
cycles of platinum-based therapy in first line.
– Adjuvant ± neoadjuvant therapy is considered 1 line
– Participants may have received a prior PARPi; this will not be considered a separate line of therapy if received in maintenance
– Participants may have received a prior 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
– Hormonal therapy for OC (eg, tamoxifen, aromatase inhibitors etc.)
will not count as a separate line of prior therapy
3. Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (ie, platinum-resistant disease).
4. Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
5. Is female, and at least 18 years of age, at the time of signing the informed consent.
6. Has an ECOG performance status of 0 to 1 assessed within 3 days before randomization.
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and:
- Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
-- Pembrolizumab: 120 days
-- Paclitaxel (or docetaxel, if applicable): 180 days
-- Bevacizumab (if administered): 180 days
The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
- Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Abs
The participant must be excluded from the study if the participant meets the following criteria:
1. Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors), borderline tumors (low malignant potential), mucinous, seromucinous that is predominantly mucinous, malignant Brenner’s tumor and undifferentiated carcinoma.
2. Has primary platinum-refractory disease, defined as disease that has
progressed per radiographic imaging while receiving or within 28 days of
the last dose of first-line platinum-based therapy.
3. Has prior disease progression on weekly paclitaxel alone.
4. Has uncontrolled hypertension.
5. Has current, clinically relevant bowel obstruction (including subocclusive disease) including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
6. Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
7. Has received >2 prior lines of systemic therapy for OC.
8. Has received prior systemic anticancer therapy, including
investigational agents or maintenance therapy (including bevacizumab
maintenance therapy), within 4 weeks before randomization.
9. Has received prior radiation therapy within 2 weeks of start of study intervention.
10. Has not recovered adequately from surgery and/or any complications from the surgery.
11. Has received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks before randomization.
12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
13. Has received an investigational agent or has used an investigational
device within 4 weeks prior to study intervention administration.
14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication.
15. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
16. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days before the first dose of study intervention.
17. Has severe hypersensitivity (=Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
18. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
20. Has an active infection requiring systemic therapy.
21. Has a known history of HIV infection.
22. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C vir
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method