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Ovarian CancerPhase 2PRECISENCT03933761

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

A Phase 2 study testing Pamiparib in people with Ovarian Cancer and Carcinosarcoma, run by Australia New Zealand Gynaecological Oncology Group.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer, Carcinosarcoma
What is being tested?
Pamiparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
29 Jul 2019to 2 Aug 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • 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
  • 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
  • Recurrent disease that is measurable according to RECIST v1.1 or evaluable disease using CA-125 according to GCIG criteria
  • 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
  • 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
  • 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
  • Patients must have recovered to ≤ grade 1 from their treatment-related adverse event (AE) with the exception of alopecia and peripheral neuropathy
  • 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

Who cannot join

  • 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
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  • 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
  • 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
  • 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
  • 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
  • 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
  • Leptomeningeal disease or uncontrolled, untreated brain metastases
  • 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
  • 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
  • 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

About this study

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

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.

Read the 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.

Being tested
Pamiparib
Keywords
High grade serous, ABCB1 fusion positive, BRCA 1/2 reversion negative, Platinum resistant, Platinum sensitive
Medical subject headings
Ovarian Neoplasms, Carcinosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PamiparibDrug

    Also called BGB-290

    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.

Study groups in NCT03933761
Study groupRoleWhat they receive
Pamiparib (BGB-290)ExperimentalDrug: Pamiparib Oral capsules 60mg twice daily continuously Although treatment is continuous, a cycle is defined as 4 weeks or 28 days.
Receives: Drug: Pamiparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical benefit rate

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

    Measured: Assessed at 16 weeks after commencing treatment.

Secondary outcomes (9)

  1. Frequency of ABCB1 fusions and BRCA1/2 reversions

    in patients with germline or somatic BRCA1/2 high grade serous cancer or carcinosarcoma

    Measured: At Baseline

  2. Median 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.

    Measured: Through study completion, on average 6 months.

  3. Median 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.

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

  4. Duration of response

    Duration of response according to RECIST v1.1 in the subset of patients who achieved partial response or complete response.

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

  5. Best overall response according to RECIST v1.1

    Best overall response is the best response from commencement of treatment according to RECIST v1.1

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

  6. Best overall response according to CA-125

    defined as best response from commencement of treatment determined by GCIG CA-125 criteria

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

  7. 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.

    Measured: 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.

  8. 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.

    Measured: 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.

  9. 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

    Measured: During the treatment period, on average 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2019
  2. Study start29 Jul 2019
  3. Primary completion2 Aug 2021
  4. Study completion2 Aug 2021

Why it stopped: No eligible patient identified after 18 evaluable patients underwent pre-screening over a 2 year period.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03933761
Sponsor's protocol ID
ANZGOG 1721/2018
Acronym
PRECISE
Status last verified
Aug 2021
First submitted
2 Apr 2019
Last updated
10 Aug 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pamiparib in people with Ovarian Cancer and Carcinosarcoma, run by Australia New Zealand Gynaecological Oncology Group.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 10 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical benefit rate (time frame: Assessed at 16 weeks after commencing treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03933761.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2021.

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