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Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer

Primary Purpose

Cervical Cancer

Status
Active
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Pembrolizumab
Olaparib
Sponsored by
Saitama Medical University International Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring cervical cancer, pembrolizumab, olaparib

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participants who are at least 20 years of age on the day of signing informed consent with histologically confirmed, recurrent or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma)
  2. Participants with confirmed disease progression during or after platinum-based chemotherapy 1 or intolerant to or ineligible for platinum-based chemotherapy or ineligible participants
  3. Participants with measurable disease based on RECIST 1.1 at screening
  4. Participant is able to provide a core or excisional biopsy of a tumor lesion for testing of PD-L1 status, etc
  5. Participants with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 upon the screening
  6. Participants who may be expected to survive at least for 12 weeks after the first dose of study drug as determined by the principal investigator or a subinvestigator
  7. Have adequate organ function

Exclusion Criteria:

  1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
  2. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the enrollment.
  3. Has received prior radiotherapy within 2 weeks prior to the enrollment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  4. Has received a live vaccine within 28 days prior to the enrollment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  5. 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 enrollment.
  6. 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 enrollment.
  7. Has a second malignancy advanced or requiring treatment within the past 3 years.The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, in situ cancers (e.g. in situ breast carcinomas).
  8. 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 the enrollment.
  9. Has severe hypersensitivity (≥Grade 3) to the study drug and/or any of its excipients.
  10. 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and participants can be enrolled in the trial.
  11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  12. Has an active infection requiring systemic therapy.
  13. Has a known history of Human Immunodeficiency Virus (HIV) infection.
  14. 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.
  15. Has a known history of active TB (Bacillus Tuberculosis).
  16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  17. Participant has received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the enrollment.
  18. Participant with clinically serious cardiovascular/cerebrovascular diseases including the following: cerebrovascular accident/stroke (less than 6 month prior to enrollment), myocardial infarction (less than 6 month prior to enrollment), unstable angina, congestive heart failure (the New York Heart Association (NYHA) Functional Classification Class 2 or severer), or serious arrhythmia. In addition, participants with history of bleeding tendency or recent major bleeding event in whom study drug administration carries higher risks as determined by the principal investigator will be excluded.
  19. Participant who have acute or chronic disease with severe and/or clinical symptoms which may compromise the tolerance to this study or competence to consistently follow the study procedures as determined by the principal investigator
  20. Participants with medical history of receiving all the PARP inhibitors
  21. Participant is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued before the study drug initiation. The required washout period prior to starting olaparib is 2 weeks.
  22. Participant is currently receiving either strong (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued before the study drug initiation. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
  23. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption).
  24. Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or participant has congenital long QT syndrome.
  25. Has a major surgery history 4 weeks prior to the enrollment (e.g.: diagnostic biopsy is not regarded as the major surgery)
  26. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  27. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit within 120 days after the last dose of trial treatment.
  28. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
  29. Participant has had an allogenic tissue/solid organ transplant

Sites / Locations

  • Saitama Medical Uiversity International Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

pembrolizumab plus olaparib

Arm Description

Until RECIST-based confirmation of progressive disease (PD), death, manifestation of intolerable toxicity, or participant withdrawal from the study, study participants will continue intravenous infusion of pembrolizumab 200 mg every three weeks (Q3W) in combination with oral olaparib 300 mg twice daily (BID) (combination therapy)

Outcomes

Primary Outcome Measures

Objective Response Rate
Objective Response Rate (ORR) will be evaluated after pembrolizumab in combination with olaparib based on RECIST 1.1.

Secondary Outcome Measures

Objective Response Rate on iRECIST
To assess ORR after administration of pembrolizumab in combination with olaparib based on iRECIST.
Duration of response
To assess duration of response (DOR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST.
Durable response rate
To assess durable response rate (DRR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST
Percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer
To assess the percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer based on RECIST 1.1 and iRECIST
PFS after administration of pembrolizumab in combination with olaparib
To assess progression-free survival (PFS) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST
Incidence of treatment-related adverse events after administration of pembrolizumab in combination with olaparib
To assess the number of participants with treatment-related adverse events after administration of pembrolizumab in combination with olaparib based on CTCAE v5.0
Objective Response Rate based on PD-L1 status
ORR will be evaluated after pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Duration of response based on PD-L1 status
To assess DOR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Durable response rate based on PD-L1 status
To assess DRR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
PFS based on PD-L1 status
To assess PFS after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.

Full Information

First Posted
November 2, 2020
Last Updated
August 8, 2022
Sponsor
Saitama Medical University International Medical Center
Collaborators
Tokyo University, National Cancer Center, Japan, Cancer Institute Hospital, Japan, Aichi Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04641728
Brief Title
Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer
Official Title
A Phase 2 Study of Pembrolizumab in Combination With Olaparib in Patients With Recurrent or Metastatic Cervical Cancer Who Had Disease Progression During or After Platinum-based Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Saitama Medical University International Medical Center
Collaborators
Tokyo University, National Cancer Center, Japan, Cancer Institute Hospital, Japan, Aichi Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

Brief Summary
This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with olaparib in recurrent or metastatic cervical cancer patients who had disease progression during or after platinum-based chemotherapy.
Detailed Description
This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with olaparib in recurrent or metastatic cervical cancer patients who had disease progression during or after platinum-based chemotherapy. This study is planned to enroll 28 patients eligible for participation from multiple study sites in Japan.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer
Keywords
cervical cancer, pembrolizumab, olaparib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
pembrolizumab plus olaparib
Arm Type
Experimental
Arm Description
Until RECIST-based confirmation of progressive disease (PD), death, manifestation of intolerable toxicity, or participant withdrawal from the study, study participants will continue intravenous infusion of pembrolizumab 200 mg every three weeks (Q3W) in combination with oral olaparib 300 mg twice daily (BID) (combination therapy)
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
KEYTRUDA
Intervention Description
pembrolizumab 200 mg every three weeks (Q3W)
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
LYNPARZA
Intervention Description
olaparib 300 mg twice daily (BID)
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
Objective Response Rate (ORR) will be evaluated after pembrolizumab in combination with olaparib based on RECIST 1.1.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Objective Response Rate on iRECIST
Description
To assess ORR after administration of pembrolizumab in combination with olaparib based on iRECIST.
Time Frame
3 years
Title
Duration of response
Description
To assess duration of response (DOR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST.
Time Frame
3 years
Title
Durable response rate
Description
To assess durable response rate (DRR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST
Time Frame
3 years
Title
Percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer
Description
To assess the percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer based on RECIST 1.1 and iRECIST
Time Frame
3 years
Title
PFS after administration of pembrolizumab in combination with olaparib
Description
To assess progression-free survival (PFS) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST
Time Frame
3 years
Title
Incidence of treatment-related adverse events after administration of pembrolizumab in combination with olaparib
Description
To assess the number of participants with treatment-related adverse events after administration of pembrolizumab in combination with olaparib based on CTCAE v5.0
Time Frame
3 years
Title
Objective Response Rate based on PD-L1 status
Description
ORR will be evaluated after pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Time Frame
3 years
Title
Duration of response based on PD-L1 status
Description
To assess DOR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Time Frame
3 years
Title
Durable response rate based on PD-L1 status
Description
To assess DRR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Time Frame
3 years
Title
PFS based on PD-L1 status
Description
To assess PFS after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Overall survival after administration of pembrolizumab in combination with olaparib based on RECIST 1.1
Description
To assess overall survival (OS) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1
Time Frame
3 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants who are at least 20 years of age on the day of signing informed consent with histologically confirmed, recurrent or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma) Participants with confirmed disease progression during or after platinum-based chemotherapy 1 or intolerant to or ineligible for platinum-based chemotherapy or ineligible participants Participants with measurable disease based on RECIST 1.1 at screening Participant is able to provide a core or excisional biopsy of a tumor lesion for testing of PD-L1 status, etc Participants with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 upon the screening Participants who may be expected to survive at least for 12 weeks after the first dose of study drug as determined by the principal investigator or a subinvestigator Have adequate organ function Exclusion Criteria: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the enrollment. Has received prior radiotherapy within 2 weeks prior to the enrollment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. Has received a live vaccine within 28 days prior to the enrollment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, 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 enrollment. 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 enrollment. Has a second malignancy advanced or requiring treatment within the past 3 years.The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, in situ cancers (e.g. in situ breast carcinomas). 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 the enrollment. Has severe hypersensitivity (≥Grade 3) to the study drug and/or any of its excipients. 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and participants can be enrolled in the trial. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Has an active infection requiring systemic therapy. Has a known history of Human Immunodeficiency Virus (HIV) infection. 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. Has a known history of active TB (Bacillus Tuberculosis). Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Participant has received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the enrollment. Participant with clinically serious cardiovascular/cerebrovascular diseases including the following: cerebrovascular accident/stroke (less than 6 month prior to enrollment), myocardial infarction (less than 6 month prior to enrollment), unstable angina, congestive heart failure (the New York Heart Association (NYHA) Functional Classification Class 2 or severer), or serious arrhythmia. In addition, participants with history of bleeding tendency or recent major bleeding event in whom study drug administration carries higher risks as determined by the principal investigator will be excluded. Participant who have acute or chronic disease with severe and/or clinical symptoms which may compromise the tolerance to this study or competence to consistently follow the study procedures as determined by the principal investigator Participants with medical history of receiving all the PARP inhibitors Participant is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued before the study drug initiation. The required washout period prior to starting olaparib is 2 weeks. Participant is currently receiving either strong (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued before the study drug initiation. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption). Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or participant has congenital long QT syndrome. Has a major surgery history 4 weeks prior to the enrollment (e.g.: diagnostic biopsy is not regarded as the major surgery) Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit within 120 days after the last dose of trial treatment. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study. Participant has had an allogenic tissue/solid organ transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kosei Hasegawa, MD, PhD
Organizational Affiliation
Saitama Medical University International Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Saitama Medical Uiversity International Medical Center
City
Hidaka
State/Province
Saitama
ZIP/Postal Code
3501298
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer

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