Pamiparib in Fusion Positive, Reversion Negative High Grade Serous Ovarian Cancer or Carcinosarcoma With BRCA1/2 Gene Mutations If Progression on Substrate Poly ADP Ribose Polymerase Inhibitbor (PARPI) or Chemotherapy (PRECISE)
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|ClinicalTrials.gov Identifier: NCT03933761|
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : August 7, 2020
This study is a phase II, multi-centre, open label study in patients with advanced ovarian cancer. The treatment being tested is Pamiparib, with daily dosing.
All patients enrolled to the study will receive treatment with pamiparib. Patients will be selected for entry into the study based on the molecular signature of their cancer.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Carcinosarcoma||Drug: Pamiparib||Phase 2|
Ovarian cancer is the deadliest gynaecologic cancer in Western women. Although initially responsive to therapy, drug resistance commonly evolves.
Novel mechanisms of drug resistance in ovarian cancer have been identified and include genetic mutations that result in the activation of a drug efflux pump and secondary mutations in BRCA1/2 genes that restore the cancer cell's ability to repair treatment related DNA damage. It is hypothesized that patients with BRCA1/2 mutant high grade serous ovarian cancer or carcinosarcoma who have progressed on recent therapy and have an activated efflux pump without a secondary BRCA1/1 mutation will be selectively sensitive to a new PARPi, Pamiparib, which does not get effluxed out of cancer cells.
The primary objective of this trial is to assess the clinical benefit rate at > 4 months in 2 cohorts of patients (cohort 1: post substrate-PARP inhibitor and cohort 2: post chemotherapy) defined as response or absence of progression. Secondary objectives are to determine the median progression free and overall survival of patients treated with Pamiparib and the impact on symptom burden and benefit.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Signal-Seeking Trial of the Clinical Benefit Rate Associated With Pamiparib in Subjects With Germline or Somatic BRCA1/2 High Grade Serous Ovarian Cancer or Carcinosarcoma Who Have Progressed on P-gp Substrate Chemotherapy or PARPi With the Presence of an ABCB1 Fusion and the Absence of a BRCA1/2 Reversion|
|Actual Study Start Date :||July 29, 2019|
|Estimated Primary Completion Date :||August 2025|
|Estimated Study Completion Date :||August 2028|
Experimental: Pamiparib (BGB-290)
Drug: Pamiparib Oral capsules 60mg twice daily continuously Although treatment is continuous, a cycle is defined as 4 weeks or 28 days.
60 mg of pamiparib (3 capsules of 20mg) will be administered orally twice a day, once in the morning and once in the evening continuously in 28 day cycles.
Other Name: BGB-290
- Clinical benefit rate [ Time Frame: Assessed at 16 weeks after commencing treatment. ]as assessed by RECIST v1.1 or by Gynaecological Cancer Intergroup (GCIG) Cancer antigen (CA)-125 criteria
- Frequency of ABCB1 fusions and BRCA1/2 reversions [ Time Frame: At Baseline ]in patients with germline or somatic BRCA1/2 high grade serous cancer or carcinosarcoma
- Median progression free survival [ Time Frame: Through study completion, on average 6 months. ]in BRCA1/2 high grade serous cancer or carcinosarcoma patients with ABCB1 fusions in the absence of BRCA1/2 reversions treated with pamiparib.
- Median overall survival [ Time Frame: Assessed for up to 3 years after the last patient enrolled has commenced treatment. ]in BRCA1/2 high grade serous cancer or carcinosarcoma patients with ABCB1 fusions in the absence of BRCA1/2 reversions treated with pamiparib.
- Duration of response [ Time Frame: Assessed for up to 3 years after the last patient enrolled has commenced treatment. ]Duration of response according to RECIST v1.1 in the subset of patients who achieved partial response or complete response.
- Best overall response according to RECIST v1.1 [ Time Frame: Assessed for up to 3 years after the last patient enrolled has commenced treatment. ]Best overall response is the best response from commencement of treatment according to RECIST v1.1
- Best overall response according to CA-125 [ Time Frame: Assessed for up to 3 years after the last patient enrolled has commenced treatment. ]defined as best response from commencement of treatment determined by GCIG CA-125 criteria
- Patient reported symptom burden [ Time Frame: At the time of consent to screening, at every cycle to 16 weeks, then every 4 cycles, and again at the time of progression. Assessed for up to 3 years after the last patient enrolled has commenced treatment. ]
Using the Measure of Ovarian Cancer Symptoms and Treatment Concerns (MOST) v2 patient reported outcome measure (PROM)
- The scale measures disease or therapy related symptoms and symptom burden and well-being
Scale ranges: Subscales are reported in five different categories with the subscale score ranges below
- Abdominal symptoms, higher values reflecting worst possible symptoms
- Disease or treatment-related symptoms, higher values reflecting worst possible symptoms
- Chemotherapy-related symptoms, higher values reflecting worst possible symptoms
- Psychological symptoms, higher values reflecting worst possible symptoms
- Well-being, higher values reflecting best possible symptoms
- Each of the 5 subscales can be scored and analysed separately (item by item) or by taking the average of the component items.
- Patient reported results of the 40 item State-trait anxiety inventory for adults (STAI-ADTM) [ Time Frame: This will be assessed 3 times - at the time of pre-screening consent, immediately prior to clinician consult with notification of pre-screening results, and immediately following notification of pre-screening results. ]
- The scale measures state level anxiety (S-Anxiety or current levels) and trait anxiety levels (T-anxiety or how someone generally feels)
- Scale ranges: STA Form Y-1 includes 20 items/questions, with a total score range of 20-80, and STA Form Y-2 includes 20 items/questions, with a total score range of 20-80. Each scored item/question is then given a weighted score of 1 to 4 with a rating of 4 indicative of a high level of anxiety for 10 x S-Anxiety items and 11 x T-Anxiety items. A high rating indicates the absences of anxiety for the remaining 10 S-Anxiety items and 9 T-Anxiety items. The scoring weights for the anxiety-present items are the same as the chosen numbers on the form and the scoring weight for the anxiety-absent items are reversed.
- For each form separately, weighted scores are then totalled and averaged. Groups of respondents will be identified (including most anxious, least anxious, and middle) based on top, bottom, and middle percentiles.
- The type, grade and relationship to treatment of adverse events [ Time Frame: During the treatment period, on average 3 years ]The type, grade and relationship to treatment of adverse events, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03933761
|Contact: Alison Freimund||+61 3 8559 email@example.com|
|Contact: John Andrews||+61 2 8071 firstname.lastname@example.org|
|Australia, New South Wales|
|Macarthur Cancer Therapy||Recruiting|
|Campbelltown, New South Wales, Australia, 2560|
|Sub-Investigator: Felicia Roncolato, Dr|
|Royal Hospital for Women / Prince of Wales||Recruiting|
|Randwick, New South Wales, Australia, 2031|
|Contact: Christie Norris Christie.Norris@health.nsw.gov.au|
|Principal Investigator: Michael Friedlander, Prof|
|Sub-Investigator: Chen Lee, Dr|
|Calvary Mater Newcastle Private||Recruiting|
|Waratah, New South Wales, Australia, 2298|
|Contact: Kim Adler Kim.Adler@calvarymater.org.au|
|Sub-Investigator: Janine Lombard, Dr|
|Mater-Brisbane||Not yet recruiting|
|Brisbane, Queensland, Australia|
|Contact: David Courtney-Rogers David.Courtney-Rodgers@mater.org.au|
|Principal Investigator: Cath Shannon, Dr|
|Monash Health VIC||Recruiting|
|Clayton, Victoria, Australia, 3168|
|Contact: Merylyn Ryan Merylyn.Ryan@monashhealth.org|
|Contact: Kelly Hoffman Kelly.Hoffman@nomashhealth.org|
|Sub-Investigator: Kate Webber, Dr|
|Peter MacCallum Cancer Centre||Recruiting|
|Melbourne, Victoria, Australia, 3000|
|Contact: Alison Freimund +61 3 85597903 email@example.com|
|Contact: Daniela Surace +61 3 85597531 firstname.lastname@example.org|
|Australia, Western Australia|
|Sir Charles Gairdner Hospital||Recruiting|
|Nedlands, Western Australia, Australia, 6009|
|Contact: Edwin Tan Edwin.Tan@health.wa.gov.au|
|Contact: Gemma Walker Gemma.Walker@health.wa.gov.au|
|Principal Investigator: Tarek Meniawy, Dr|
|Principal Investigator:||Alison Freimund||Peter MacCallum Cancer Centre, Australia|