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 |
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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 |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 2026 |
Estimated Study Completion Date : | August 2029 |
Arm | Intervention/treatment |
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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.
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Drug: Pamiparib
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
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Using the Measure of Ovarian Cancer Symptoms and Treatment Concerns (MOST) v2 patient reported outcome measure (PROM)
Scale ranges: Subscales are reported in five different categories with the subscale score ranges below
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Gender Based Eligibility: | Yes |
Gender Eligibility Description: | Female patients with high grade serous ovarian cancinoma or carcinosarcoma. |
Accepts Healthy Volunteers: | No |
Inclusion Criteria - Pre-Screening
Patients with a histopathological diagnosis of HGSC or carcinosarcoma of the ovary (including primary peritoneal cancers and fallopian tube cancers) as defined by histological diagnosis and immunohistochemistry (IHC) and with a germline or somatic BRCA1/2 mutation:
Patients with progressive disease defined by GCIG CA-125 and/or RECIST v1.1 criteria after 3 or more lines of chemotherapy or after progression on a P-gp substrate PARPi (i.e.
olaparib, niraparib)
Disease that is amenable to a biopsy and/or ascitic drainage
Exclusion Criteria - Pre-Screening
Prior treatment with non-substrate P-gp PARPi (pamiparib or veliparib)
Patient has other diagnoses of malignancy
Previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease-causing malabsorption syndrome
Inclusion Criteria - Main Study
Patient has platinum sensitive or platinum resistant HGSC
Adequate haematologic and end-organ function, as defined by the following laboratory results (obtained within 7 days prior to registration to the main study):
Females who are of childbearing potential
Able to provide a formalin-fixed paraffin embedded (FFPE) tumour block, representative of the patient's primary disease
Exclusion Criteria - Main Study
Patients who have received chemotherapy, biologic therapy, immunotherapy, investigational agent, anticancer Chinese medicine, or herbal remedies ≤ 5 half-lives if the half-life is known, ≤ 14 days if not known, prior to registration to the main study
Major surgical procedure, open biopsy, or significant traumatic injury ≤ 14 days prior to registration to the main study, or anticipation of need for major surgical procedure during the course of the study
Patients with a history of treated and asymptomatic brain metastases are eligible, provided they meet all of the following:
Any of the following cardiovascular criteria:
Active infection requiring systemic treatment, acute/viral hepatitis or active chronic hepatitis B or C or active tuberculosis
Contact: Alison Freimund | +61 3 8559 7903 | ali.freimund@petermac.org | |
Contact: John Andrews | +61 2 8071 4881 | trials@anzgog.org.au |
Australia, New South Wales | |
Macarthur Cancer Therapy | Recruiting |
Campbelltown, New South Wales, Australia, 2560 | |
Contact: Melissa Fox Melissa.fox1@health.nsw.gov.au | |
Sub-Investigator: Felicia Roncolato, Dr | |
Sub-Investigator: Diana Adams, Dr | |
Sub-Investigator: Sarah Khan, Dr | |
Sub-Investigator: Kay Xu, Dr | |
Principal Investigator: Shalini Subramaniam, Dr | |
Royal Hospital for Women / Prince of Wales | Recruiting |
Randwick, New South Wales, Australia, 2031 | |
Contact: Umuhan Cet Umuhan.Cet@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: Sue Brew Sue.Brew@calvarymater.org.au | |
Contact: Kim Adler Kim.Adler@calvarymater.org.au | |
Sub-Investigator: Janine Lombard, Dr | |
Sub-Investigator: Tony Bonaventura, Dr | |
Sub-Investigator: Hiren Mandaliya, Dr | |
Australia, Queensland | |
Mater-Brisbane | Not yet recruiting |
Brisbane, Queensland, Australia | |
Contact: David Courtney-Rogers David.Courtney-Rodgers@mater.org.au | |
Principal Investigator: Cath Shannon, Dr | |
Australia, Victoria | |
Monash Health VIC | Recruiting |
Clayton, Victoria, Australia, 3168 | |
Contact: Halli Waran Halli.Waran@monashhealth.org | |
Contact: Team Email breastgynae.oncresearch@monashhealth.org | |
Sub-Investigator: Kate Webber, Dr | |
Sub-Investigator: Sophia Frentzas, Dr | |
Sub-Investigator: Gwo Ho, Dr | |
Sub-Investigator: Caroline Lum, Dr | |
Sub-Investigator: Yeojeong So, Dr | |
Peter MacCallum Cancer Centre | Recruiting |
Melbourne, Victoria, Australia, 3000 | |
Contact: Alison Freimund +61 3 85597903 ali.freimund@petermac.org | |
Contact: Amanda Seegum +61 3 85597531 amanda.seegum@petermac.org | |
Sub-Investigator: Linda Mileshkin, Asoc Prof | |
Australia, Western Australia | |
Sir Charles Gairdner Hospital | Recruiting |
Nedlands, Western Australia, Australia, 6009 | |
Contact: Hamza Cakan Hamza.Cakan@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 |
Tracking Information | |||||||||
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First Submitted Date ICMJE | April 2, 2019 | ||||||||
First Posted Date ICMJE | May 1, 2019 | ||||||||
Last Update Posted Date | March 23, 2021 | ||||||||
Actual Study Start Date ICMJE | July 29, 2019 | ||||||||
Estimated Primary Completion Date | August 2026 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | 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 | ||||||||
Official Title ICMJE | 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 | ||||||||
Brief Summary |
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. |
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Detailed Description |
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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: Pamiparib
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
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Study Arms ICMJE | 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.
Intervention: Drug: Pamiparib
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
40 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | August 2029 | ||||||||
Estimated Primary Completion Date | August 2026 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria - Pre-Screening
Exclusion Criteria - Pre-Screening
Inclusion Criteria - Main Study
Exclusion Criteria - Main Study
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Australia | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03933761 | ||||||||
Other Study ID Numbers ICMJE | ANZGOG 1721/2018 | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Australia New Zealand Gynaecological Oncology Group | ||||||||
Study Sponsor ICMJE | Australia New Zealand Gynaecological Oncology Group | ||||||||
Collaborators ICMJE | BeiGene | ||||||||
Investigators ICMJE |
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PRS Account | Australia New Zealand Gynaecological Oncology Group | ||||||||
Verification Date | March 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |