Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer (BRIGHT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05044871
Recruitment Status : Not yet recruiting
First Posted : September 16, 2021
Last Update Posted : October 14, 2021
Sponsor:
Collaborators:
Qilu Hospital of Shandong University
Hubei Cancer Hospital
Hunan Cancer Hospital
Beijing Cancer Hospital
Obstetrics and Gynecology Hospital of Zhejiang University
Sun Yat-sen University
Anhui Provincial Cancer Hospital
Jilin Provincial Tumor Hospital
First Affiliated Hospital, Sun Yat-Sen University
Affiliated Hospital of Jiangnan University
Information provided by (Responsible Party):
Qinglei Gao, Tongji Hospital

Tracking Information
First Submitted Date  ICMJE September 9, 2021
First Posted Date  ICMJE September 16, 2021
Last Update Posted Date October 14, 2021
Estimated Study Start Date  ICMJE January 1, 2022
Estimated Primary Completion Date June 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2021)
Objective response rate (ORR) [ Time Frame: Up to 3 years ]
ORR is defined as the proportion of patients with complete response(CR) and partial response(PR) assessed by the investigator in accordance with the RECIST 1.1 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2021)
  • Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
    PFS is defined as the time from enrollment to the first imaging disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator.
  • Overall survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time between enrollment and the patient's death due to any cause.
  • Disease control rate (DCR) [ Time Frame: Up to 5 years ]
    DCR is defined as the proportion of the patients with complete response, partial remission, and stable disease after treatment. Assessed according to RECIST v1.1 by investigator.
  • Duration of remission (DOR) [ Time Frame: Up to 3 years ]
    DOR is defined as the time interval from the first record of disease response to disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator.
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Up to 5 years ]
    Safety includes the adverse event profile of all drugs included according to the Common Terminology Criteria for Adverse Events version 5.0.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2021)
  • Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
    PFS is defined as the time from enrollment to the first imaging disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator.
  • Overall survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time between enrollment and the patient's death due to any cause.
  • Disease control rate (DCR) [ Time Frame: Up to 5 years ]
    DCR is defined as the proportion of the patients with complete response, partial remission, and stable disease after treatment. Assessed according to RECIST v1.1 by investigator.
  • Duration of remission (DOR) [ Time Frame: Up to 3 years ]
    DOR is defined as the time interval from the first record of disease response to disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by investigator.
  • Safety of therapies [ Time Frame: Up to 5 years ]
    Safety includes the adverse event profile of all drugs included according to the Common Terminology Criteria for Adverse Events version 5.0.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer
Official Title  ICMJE The Efficiency of Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer (PROC): An Umbrella Study
Brief Summary This study is an open-label, multicenter, umbrella study aimed to evaluate the combined, biomarker-driven, targeted treatment efficiency of Pamiparib, Bevacizumab, Tislelizumab, and Nab-paclitaxel in patients with platinum-resistant recurrent ovarian cancer (PROC).
Detailed Description

BRCA1/2 gene status and CD8+ tumor-infiltrating T cell count (CD8 + TILs count) were evaluated as biomarkers using archived tumor tissue samples. Treatment arms were arranged according to pathological diagnosis and biomarker detection results.

Arm1 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).

Arm2 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w).

Arm3 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 wildtype and <3 CD8+ TILs count): Bevacizumab 7.5mg/kg IV D1, 15 + Nab-paclitaxel 100mg / m2 IV D1, 8, 15 (Q4w).

Arm4 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: ≥3 CD8+ TILs count): Tislelizumab 200mg IV D1 + Bevacizumab 7.5mg/kg IV D1 + Nab-paclitaxel 125mg / m2 IV D1, 8 (q3w).

Arm5 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: <3 CD8+ TILs count: Bevacizumab 7.5mg/kg IV. D1, 15 + Nab-paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).

Treatment would continue until disease progression, intolerable toxicity, death, withdrawal of consent, or sponsor termination of the study, whichever occurs first.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • Drug: Pamiparib
    40mg PO. bid.
  • Drug: Bevacizumab
    7.5mg/kg IV. D1 (q3w.)
  • Drug: Tislelizumab
    200mg IV. D1
  • Drug: Nab paclitaxel
    125mg / m2 IV. D1, 8 (q3w).
  • Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)
    Bevacizumab 7.5mg/kg IV. D1, 15 (Q4w). + Nab paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).
Study Arms  ICMJE
  • Experimental: Arm 1: Pamiparib+ Bevacizumab
    Arm1 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).
    Interventions:
    • Drug: Pamiparib
    • Drug: Bevacizumab
  • Experimental: Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel
    Arm2 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w).
    Interventions:
    • Drug: Bevacizumab
    • Drug: Tislelizumab
    • Drug: Nab paclitaxel
  • Experimental: Arm 3: Bevacizumab + Nab-paclitaxel
    Arm3 (Pathological classification: Serous, Endometrioid, and Clear cell Ovarian cancer; Biomarkers: BRCA 1/2 wildtype and <3 CD8+ TILs count): Bevacizumab 7.5mg/kg IV D1, 15 + Nab-paclitaxel 100mg / m2 IV D1, 8, 15 (Q4w).
    Intervention: Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)
  • Experimental: Arm 4: Tislelizumab + Bevacizumab + Nab-paclitaxel
    Arm4 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: ≥3 CD8+ TILs count): Tislelizumab 200mg IV D1 + Bevacizumab 7.5mg/kg IV D1 + Nab-paclitaxel 125mg / m2 IV D1, 8 (q3w).
    Interventions:
    • Drug: Bevacizumab
    • Drug: Tislelizumab
    • Drug: Nab paclitaxel
  • Experimental: Arm 5: Bevacizumab + Nab-paclitaxel
    Arm5 (Pathological classification: Mucinous Ovarian cancer, Ovarian carcinosarcoma; Biomarkers: <3 CD8+ TILs count: Bevacizumab 7.5mg/kg IV. D1, 15 + Nab-paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).
    Intervention: Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2021)
160
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2027
Estimated Primary Completion Date June 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Voluntary participation and signing of informed consent
  2. Age ≥ 18 years;
  3. the Eastern United States cancer cooperation group (ECoG) score 0-1;
  4. Platinum-resistant recurrent ovarian cancer (PROC): the patient was diagnosed with platinum-resistant recurrence for the first time. PROC refers to the disease progression that occurred < 6 months after the last dose of platinum-based chemotherapy. Imaging-based evaluation for the latest recurrence/progression before enrollment was required;
  5. Malignant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer confirmed by histology or cytology, including high-grade serous cancer, low-grade serous cancer, endometrioid cancer, clear cell cancer, mucinous cancer, and carcinosarcoma;
  6. Biomarker detection and tumor sample collection meet the following standards:

    • Patients must provide archived tumor tissue samples (formalin-fixed, paraffin-embedded tumor tissue blocks [preferred], or about 20 unstained tissue sections), except for patients with serous carcinoma, endometrioid carcinoma, clear cell carcinoma and gBRCAm
    • If the patient has been tested for BRCA1 / 2 gene in the past, only the corresponding test report needs to be provided
  7. Sufficient organ functions, which is defined as:

    • neutrophil absolute value (ANC) ≥ 1.5 × 109/L
    • platelet count (PLT) ≥ 75 × 10*9/L
    • hemoglobin ≥ 9 g / dl
    • serum creatinine CR < 1.5 × Upper normal value (ULN)
    • total serum bilirubin ≤ 1.5 × Upper normal range (ULN)
    • both aspartate aminotransferase and alanine aminotransferase ≤ 3 × ULN
    • coagulation function: international normalized ratio (INR) ≤ 1.5; Activated partial prothrombin time (APTT) ≤ 1.5 × ULN
  8. Patients must have lesions that can be measured according to RECIST v1.1 standard;
  9. Participants were allowed to have previously VEGF / VEGFR inhibitors treatment, but the proportion of these patients would not exceed 20%;
  10. Participants were allowed to have previously PARP inhibitors treatment. However, for treatment arm 1 (arm1), the exposure time of PARP inhibitors should ≥ 12 months after first-line chemotherapy or ≥ 6 months after second-line and above chemotherapy;
  11. Life expectancy ≥ 3 months;

Exclusion Criteria:

  1. The exclusion criteria of bevacizumab were clinically significant cardiovascular and cerebrovascular diseases, history of abdominal fistula or gastrointestinal perforation, acute intestinal obstruction or sub obstruction, and active bleeding;
  2. Uncontrolled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) or clinically significant (active) cardiovascular disease: cerebrovascular accident (CVA) / stroke ≤ 6 months from the treatment of the first clinical study; Myocardial infarction ≤ 6 months from the first clinical study treatment; Unstable angina pectoris; Congestive heart failure (CHF) of grade II or above in the cardiac function classification standard of the New York Heart Association (NYHA); Serious arrhythmias requiring treatment;
  3. Previous medical history showed newly discovered thrombotic diseases within 6 months before or during the screening period; Patients with severe wound nonunion, ulcer, or fracture;
  4. Major surgery within 30 days before the first administration of study treatment; Patients expected to have invasive surgery during treatment;
  5. Patients with other malignant tumors;
  6. Patients who have previously received anti-programmed cell death protein-1 (anti-PD-1), anti-programmed death ligand-1 (anti-PD-L1) or anti-PD-L2 drugs, or another drug treatment for T cell inhibitory receptors (e.g., cytotoxic T lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (tnfrsf9)];
  7. Active autoimmune diseases requiring systemic treatment in the past 2 years;
  8. Any case requiring systemic treatment with corticosteroids (prednisone or equivalent > 10 mg/day) or other immunosuppressive drugs ≤ 14 days before the first administration of the study drug;
  9. Known history of human immunodeficiency virus (HIV) infection;
  10. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA > 500 IU / ml) or active HCV carriers with detectable HCV RNA; Note: inactive hepatitis B surface antigen (HBsAg) carriers and treated and stable hepatitis B patients (HBV DNA < 500 IU / ml) can be included in the group;
  11. History of interstitial lung disease, noninfectious pneumonia, or uncontrolled diseases, including pulmonary fibrosis, acute lung disease, etc;
  12. Previous heterologous stem cell transplantation or organ transplantation;
  13. Peripheral neuropathy ≥ grade 2;
  14. Foods or drugs that are expected to use CYP3A4 strong inducers or strong inhibitors within 28 days before the use of the study drug;
  15. Participate in another clinical study at the same time, unless it is an observational (non-intervention) clinical study or is in the follow-up period of intervention study;
  16. Women of childbearing age who are unwilling or unable to use effective methods for contraception during the whole treatment period of this trial and within 6 months after the last administration of the study drug [women of childbearing age include: any women who have had menarche and have not undergone successful artificial sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or premenopausal], pregnant or lactating women.
  17. Other conditions judged by the researcher that do not meet the enrollment requirements.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Qinglei Gao, MD. PhD 15391566981 qingleigao@hotmail.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05044871
Other Study ID Numbers  ICMJE 2021-TJ-PROC
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Qinglei Gao, Tongji Hospital
Study Sponsor  ICMJE Tongji Hospital
Collaborators  ICMJE
  • Qilu Hospital of Shandong University
  • Hubei Cancer Hospital
  • Hunan Cancer Hospital
  • Beijing Cancer Hospital
  • Obstetrics and Gynecology Hospital of Zhejiang University
  • Sun Yat-sen University
  • Anhui Provincial Cancer Hospital
  • Jilin Provincial Tumor Hospital
  • First Affiliated Hospital, Sun Yat-Sen University
  • Affiliated Hospital of Jiangnan University
Investigators  ICMJE
Principal Investigator: Qinglei Gao, MD. PhD Tongji Hospital
PRS Account Tongji Hospital
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP