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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03933761




Registration number
NCT03933761
Ethics application status
Date submitted
2/04/2019
Date registered
1/05/2019

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
ANZGOG 1721/2018
Universal Trial Number (UTN)
Trial acronym
PRECISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Carcinosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pamiparib

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.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical benefit rate
Timepoint [1] 0 0
Assessed at 16 weeks after commencing treatment.
Secondary outcome [1] 0 0
Frequency of ABCB1 fusions and BRCA1/2 reversions
Timepoint [1] 0 0
At Baseline
Secondary outcome [2] 0 0
Median progression free survival
Timepoint [2] 0 0
Through study completion, on average 6 months.
Secondary outcome [3] 0 0
Median overall survival
Timepoint [3] 0 0
Assessed for up to 3 years after the last patient enrolled has commenced treatment.
Secondary outcome [4] 0 0
Duration of response
Timepoint [4] 0 0
Assessed for up to 3 years after the last patient enrolled has commenced treatment.
Secondary outcome [5] 0 0
Best overall response according to RECIST v1.1
Timepoint [5] 0 0
Assessed for up to 3 years after the last patient enrolled has commenced treatment.
Secondary outcome [6] 0 0
Best overall response according to CA-125
Timepoint [6] 0 0
Assessed for up to 3 years after the last patient enrolled has commenced treatment.
Secondary outcome [7] 0 0
Patient reported symptom burden
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Patient reported results of the 40 item State-trait anxiety inventory for adults (STAI-ADTM)
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
The type, grade and relationship to treatment of adverse events
Timepoint [9] 0 0
During the treatment period, on average 3 years

Eligibility
Key inclusion criteria
Inclusion Criteria - Pre-Screening

1. Patient has provided written informed consent for pre-screening
2. Patient is able to comply with the study protocol and follow-up procedures, in the Investigator's judgement
3. Patient is female aged = 18 years at time of consent
4. ECOG performance status 0-2 (refer to Appendix 1)
5. 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
6. 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
7. 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)
8. 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
9. Patient has a life expectancy > 12 weeks
10. Patient has consented to the collection and use of their fresh tumour biopsies and/or ascites samples
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria - Pre-Screening

1. Patients with a clear cell, mucinous, or other non-high grade serous histological subtype
2. Prior treatment with non-substrate P-gp PARPi (pamiparib or veliparib)

* Prior treatment with substrate PARPi is allowed (olaparib, niraparib, rucaparib, and talazoparib)
3. Patients who are pregnant or nursing
4. Patient has a diagnosis of myelodysplastic syndrome (MDS)
5. 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
6. Prior radiation therapy to target lesions in the absence of documented progression at the treated target lesion
7. Patient has uncontrolled pleural effusion, pericardial effusion, or ascites requiring weekly recurrent drainage procedures
8. Known history of intolerance to the excipients of the pamiparib capsule
9. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena =6 months prior to registration to pre-screening
10. 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

Inclusion Criteria - Main Study

1. Patient has provided written informed consent for main PRECISE study
2. Patient continues to meet all pre-screening inclusion criteria
3. Patient has an ABCB1 fusion(s) and the absence of a BRCA1/2 reversion
4. Patient has platinum sensitive or platinum resistant HGSC

* Patients who are refractory (progress during or within 4 weeks) to second or subsequent lines of platinum-based chemotherapy are eligible
* Patients who are primary platinum refractory (progress during or within 4 weeks of first line chemotherapy) are considered ineligible
5. Recurrent disease that is measurable according to RECIST v1.1 or evaluable disease using CA-125 according to GCIG criteria
6. Adequate haematologic and end-organ function, as defined by the following laboratory results (obtained within 7 days prior to registration to the main study):

* Absolute neutrophil count (ANC) =1.5 x 109/L
* Platelet count = 100 x 109/L
* Haemoglobin (Hb) = 90 g/L (= 28 days after transfusion)
* Estimated glomerular filtration rate = 30 mL/min/1.73 m2 by the Modification of Diet in Renal Disease study equation (MDRD STUDY EQ; www.mdrd.com or Appendix 5)
* Total serum bilirubin = 1.5 x upper limit of normal (ULN)
* = 4 x ULN, if Gilbert's syndrome or if indirect bilirubin concentrations suggestive of extrahepatic source of elevation
* Aspartate and alanine aminotransferase (AST and ALT) = 3 x upper limit of normal (ULN) or = 5 x ULN for patients with liver metastases
7. Females who are of childbearing potential

* Females of childbearing potential require a negative serum pregnancy test within 7 days prior to registration into the main study
8. Females of childbearing potential must practice highly effective methods of birth control (refer to Appendix 2) for the duration of the study and for at least 6 months after last study drug
9. Patients must have recovered to = grade 1 from their treatment-related adverse event (AE) with the exception of alopecia and peripheral neuropathy
10. Able to provide a formalin-fixed paraffin embedded (FFPE) tumour block, representative of the patient's primary disease

* In cases where there is insufficient FFPE tumour, a discussion with the Coordinating Principal Investigator (CPI) must be had before registration to the main study

Exclusion Criteria - Main Study

1. 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

* Bisphosphonate and denosumab use are allowed on study, if administered at a stable dose > 28 days prior to registration to the main study
2. The use or anticipated need for food or drugs known to be strong CYP3A inducers (Appendix 7) = 5 half-lives if the half-life is known or = 14 days if not known prior to registration to the main study
3. 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

* Placement of vascular access device is not considered major surgery
4. Prior radiation therapy = 14 days prior to registration to the main study to non-target lesions. Patients who have received palliative radiotherapy of non-target lesions for local symptom control > 14 days prior to registration to the main study must have stabilisation of any AEs or a return to baseline prior to registration to the main study
5. Leptomeningeal disease or uncontrolled, untreated brain metastases
6. Patients with a history of treated and asymptomatic brain metastases are eligible, provided they meet all of the following:

* Only supratentorial metastases
* Brain imaging at screening without evidence of interim progression
* No ongoing requirement for corticosteroids as therapy for brain metastases
* Anticonvulsants at a stable dose allowed (except for contraindicated medications carbamazepine and phenytoin)
* No stereotactic radiation or whole-brain radiation = 14 days prior to registration to the main study
7. Any of the following cardiovascular criteria:

* Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, = 28 days prior to registration to the main study
* Symptomatic pulmonary embolism = 28 days prior to registration to the main study
* Any history of acute myocardial infarction = 6 months prior to registration to the main study
* Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV (refer to Appendix 8) = 6 months prior to registration to the main study
* Any event of ventricular arrhythmia = Grade 2 in severity = 6 months prior to registration to the main study
* Any history of cerebrovascular accident (CVA) = 6 months prior to registration to the main study
8. Active infection requiring systemic treatment, acute/viral hepatitis or active chronic hepatitis B or C or active tuberculosis

* Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is > 500 IU/mL or patients with active hepatitis C should be excluded. Note: Inactive hepatitis B surface antigen carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL), and cured hepatitis C patients can be enrolled

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/08/2021
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Other
Name
Australia New Zealand Gynaecological Oncology Group
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
BeiGene
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alison Freimund
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03933761