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

NCT03933761 | Withdrawn Phase 2

• 1 other identifier: ANZGOG 1721/2018
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ovarian Cancer; Carcinosarcoma

Keywords

High grade serous; ABCB1 fusion positive; BRCA 1/2 reversion negative; Platinum resistant; Platinum sensitive

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate

  as assessed by RECIST v1.1 or by Gynaecological Cancer Intergroup (GCIG) Cancer antigen (CA)-125 criteria

  Assessed at 16 weeks after commencing treatment.

Secondary Outcomes (9)

• Frequency of ABCB1 fusions and BRCA1/2 reversions

  At Baseline

• Median progression free survival

  Through study completion, on average 6 months.

• Median overall survival

  Assessed for up to 3 years after the last patient enrolled has commenced treatment.

• Duration of response

  Assessed for up to 3 years after the last patient enrolled has commenced treatment.

• Best overall response according to RECIST v1.1

  Assessed for up to 3 years after the last patient enrolled has commenced treatment.

Study Arms (1)

Pamiparib (BGB-290)

EXPERIMENTAL

Drug: Pamiparib Oral capsules 60mg twice daily continuously Although treatment is continuous, a cycle is defined as 4 weeks or 28 days.

Drug: Pamiparib

Interventions

Pamiparib DRUG

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.

Also known as: BGB-290

Pamiparib (BGB-290)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients with high grade serous ovarian cancinoma or carcinosarcoma.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent for pre-screening
• Patient is able to comply with the study protocol and follow-up procedures, in the Investigator's judgement
• Patient is female aged ≥ 18 years at time of consent
• ECOG performance status 0-2 (refer to Appendix 1)
• Patient has the ability to take oral medications without medical history of malabsorption or other chronic gastrointestinal disease, or other conditions that may harm compliance and/or absorption of the study agent
• 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:
• Mixed histologies are allowed provided that \>80% of the primary tumour is a HGSC based on diagnostic pathology review and IHC profile
• 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)
• Patients may continue on treatment as per standard of care by their usual clinician while awaiting the results of pre-screening with no impact on usual care
• Patients who have been treated with both substrate PARPi and substrate chemotherapy will be considered eligible for either cohort 1 or cohort 2 based on the therapy they have most recently progressed on (cohort 1 is progression on PARPi and cohort 2 is progression on chemotherapy)
• Disease that is amenable to a biopsy and/or ascitic drainage
• Lesions intended to be biopsied should not be target lesions with the preference of the biopsy site having progressed on most recent imaging where clinically safe and feasible
• Patient has a life expectancy \> 12 weeks
• Patient has consented to the collection and use of their fresh tumour biopsies and/or ascites samples

You may not qualify if:

• Patients with a clear cell, mucinous, or other non-high grade serous histological subtype
• Prior treatment with non-substrate P-gp PARPi (pamiparib or veliparib)
• Prior treatment with substrate PARPi is allowed (olaparib, niraparib, rucaparib, and talazoparib)
• Patients who are pregnant or nursing
• Patient has a diagnosis of myelodysplastic syndrome (MDS)
• Patient has other diagnoses of malignancy
• Except for surgically excised non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated non-invasive bladder cancer, ductal carcinoma in situ treated surgically with curative intent, or a malignancy diagnosed \>2 years ago with no current evidence of disease and no therapy ≤2 years prior to pre-screening
• Prior radiation therapy to target lesions in the absence of documented progression at the treated target lesion
• Patient has uncontrolled pleural effusion, pericardial effusion, or ascites requiring weekly recurrent drainage procedures
• Known history of intolerance to the excipients of the pamiparib capsule
• Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena ≤6 months prior to registration to pre-screening
• Previous complete gastric resection, chronic diarrhea, active inflammatory gastrointestinal disease, or any other disease-causing malabsorption syndrome
• Gastroesophageal reflux disease under treatment with proton-pump inhibitors is allowed
• Patient has provided written informed consent for main PRECISE study
• Patient has an ABCB1 fusion(s) and the absence of a BRCA1/2 reversion

Sponsors & Collaborators

• Australia New Zealand Gynaecological Oncology Group: lead
• BeiGene: collaborator

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinosarcoma

Interventions

pamiparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue

Study Officials

• Alison Freimund

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: May 1, 2019
• Study Start: July 29, 2019
• Primary Completion: August 2, 2021
• Study Completion: August 2, 2021
• Last Updated: August 10, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share