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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03933761
Ethics application status
Date submitted
2/04/2019
Date registered
1/05/2019
Date last updated
2/08/2019

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 - as assessed by RECIST v1.1 or by Gynaecological Cancer Intergroup (GCIG) Cancer antigen (CA)-125 criteria
Timepoint [1] 0 0
Assessed at 16 weeks after commencing treatment.
Secondary outcome [1] 0 0
Frequency of ABCB1 fusions and BRCA1/2 reversions - in patients with germline or somatic BRCA1/2 high grade serous cancer or carcinosarcoma
Timepoint [1] 0 0
At Baseline
Secondary outcome [2] 0 0
Progression free survival - in BRCA1/2 high grade serous cancer or carcinosarcoma patients with ABCB1 fusions in the absence of BRCA1/2 reversions treated with pamiparib.
Timepoint [2] 0 0
Through study completion, on average 6 months.
Secondary outcome [3] 0 0
Overall survival - in BRCA1/2 high grade serous cancer or carcinosarcoma patients with ABCB1 fusions in the absence of BRCA1/2 reversions treated with pamiparib.
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 - Duration of response according to RECIST v1.1 in the subset of patients who achieved partial response or complete 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 - Best overall response is the best response from commencement of treatment 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 - defined as best response from commencement of treatment determined by GCIG CA-125 criteria
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 - 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.
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) - 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.
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 - 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
Timepoint [9] 0 0
During the treatment period, on average 3 years

Eligibility
Key inclusion criteria
Inclusion Criteria - Pre-Screening

- Patient has provided written informed consent for the Pre-Screening part of the study

- Patient is able to comply with the study protocol and follow-up procedures, in the
investigator's judgement

- Patient is female aged at least 18 years at screening

- ECOG performance status 0-2

- Ability to swallow whole capsules

- Patients with a histopathological diagnosis of High Grade Serous Ovarian Carcinoma 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:

a. Mixed histologies are allowed provided that >80% of the primary tumour is a high
grade serous ovarian carcinoma based on diagnostic pathology review and IHC profile

- Progressive symptomatic or asymptomatic recurrent disease defined by GCIG CA- 125
and/or RECIST v1.1 criteria after > 1 line of chemotherapy and/or after P-gp substrate
PARPi provided that the patient must not have progressed nor had recurrent disease
within 6 months of the completion of the last platinum-containing regimen

1. 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.

2. 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) provided that the patient must
not have progressed nor had recurrent disease within 6 months of the completion
of the last platinum-containing regimen via RECIST v1.1 criteria.

- Disease that is measurable according to RECIST v1.1 or evaluable disease using CA-125
according to GCIG criteria

- Disease that is amenable to a biopsy and/or ascitic drainage (note that 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

Inclusion Criteria - Main Study

- Patient has provided written informed consent for main PRECISE study

- Patient continues to meet all pre-screening inclusion criteria

- Patient has an ABCB1 fusion(s) and the absence of a BRCA1/2 reversion

- Adequate haematologic and end-organ function, as defined by the following laboratory
results (obtained = 14 days before start of pamiparib on Day 1)

- Absolute neutrophil count (ANC) =1.5 x 109/L

- Platelet count = 100 x 109/L

- Haemoglobin (Hb) = 9 g/dL (= 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)

- 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

- Females of childbearing potential must practice highly effective methods of birth
control (Appendix 1) for the duration of the study and for at least 6 months after
last study drug

- Patients must have recovered to = grade 1 from their treatment-related adverse event
(AE) with the exception of alopecia and peripheral neuropathy

- Patient has consented to the use of their collected fresh tumour biopsies, archival
FFPE specimen, ascites and peripheral blood samples as detailed in the protocol for
translational research, including but not limited to DNA, RNA and protein-based
biomarker detection.

- Able to provide a formalin-fixed paraffin embedded (FFPE) tumour block, representative
of the participant's primary disease, which must be forwarded to the Central
Laboratory within 20 working days post registration.

1. In cases where there is insufficient FFPE tumour, a discussion with the
coordinating principal investigator (CPI) must be had before consent into the
main study.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with a clear cell, mucinous, or other non-high grade serous histological
subtype

- Prior treatment with non-substrate P-gp PARPi

a. Prior treatment with substrate PARPi is allowed (Olaparib, Niraparib, Rucaparib,
and Talazoparib)

- Leptomeningeal disease or uncontrolled, untreated brain metastases

a. Patients with a history of treated and asymptomatic brain metastases are eligible,
provided they meet all of the following: i. Only supratentorial metastases ii. Brain
imaging at screening without evidence of interim progression iii. No ongoing
requirement for corticosteroids as therapy for brain metastases [Anticonvulsants at a
stable dose allowed (except for contraindicated medications carbamazepine and
phenytoin)] iv. No stereotactic radiation or whole-brain radiation = 14 days before
Day 1

- Patients who are pregnant or nursing

a. Females of childbearing potential require a negative serum pregnancy test = 7 days
before Day 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

a. Bisphosphonate and denosumab use is allowed on study, if administered at a stable
dose > 28 days prior to registration.

- The use or anticipated need for food or drugs known to be strong or moderate
cytochrome P450 (CYP) 3A inhibitors or strong CYP3A inducers = 5 half-lives if the
half-life is known or = 14 days if not known prior to registration

- Major surgical procedure, open biopsy, or significant traumatic injury = 14 days prior
to registration, or anticipation of need for major surgical procedure during the
course of the study

a. Placement of vascular access device is not considered major surgery

- Patient has a diagnosis of Myelodysplastic Syndrome (MDS)

- Patient has other diagnoses of malignancy

a. 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 registration

- Prior radiation therapy to target lesions

- Prior radiation therapy = 14 days before start of pamiparib on Day 1 to non-target
lesions. Patients who have received palliative radiotherapy of non-target lesions for
local symptom control > 14 days before start of pamiparib must have stabilisation of
any AEs or a return to baseline prior to the start of pamiparib

- Patient has uncontrolled pleural effusion, pericardial effusion, or ascites requiring
weekly recurrent drainage procedures

- Active infection requiring systemic treatment, acute/viral hepatitis or active chronic
hepatitis B or C or active tuberculosis

a. 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.

- 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

- Previous complete gastric resection, chronic diarrhea, active inflammatory
gastrointestinal disease, or any other disease-causing malabsorption syndrome

a. Gastroesophageal reflux disease under treatment with proton-pump inhibitors is
allowed.

- Any of the following cardiovascular criteria:

1. Cardiac chest pain, defined as moderate pain that limits instrumental activities
of daily living, = 28 days prior to registration

2. Symptomatic pulmonary embolism = 28 days prior to registration

3. Any history of acute myocardial infarction = 6 months prior to registration

4. Any history of heart failure meeting New York Heart Association (NYHA)
Classification III or IV = 6 months prior to registration

5. Any event of ventricular arrhythmia = Grade 2 in severity = 6 months prior to
registration

6. Any history of cerebrovascular accident (CVA) = 6 months prior to registration

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Australia New Zealand Gynaecological Oncology Group
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03933761
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
Alison Freimund
Address 0 0
Country 0 0
Phone 0 0
+61 3 8559 7903
Fax 0 0
Email 0 0
ali.freimund@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03933761