None listed
Conditions
Brief summary
This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program, which is registered on ANZCTR with ID ACTRN12515000908437. This substudy will evaluate the activity of pamiparib in participants with acute myloid leukaemia or myelodysplastic syndrome with DNA repair pathway mutation (e.g. BRCA1/2), and/or BRCA mutational signature. Who is it for? You may be eligible to join the study if you are aged 18 years and older, with acute myeloid leukaemia or myelodysplastic syndrome. Your cancer will need to harbour DNA repair pathway mutations (e.g. BRCA1/2), and/or BRCA mutational signature. Study details: Participants will receive pamiparib, to be taken orally at a dose of 60 mg twice daily. Pamiparib will be given to participants continuously as long as they and their doctor agree there is a benefit from treatment. Participants will undergo clinical assessments at 4 weekly intervals from first treatment until end of treatment.. Safety and tolerability of treatment will be assessed at 4 weekly intervals. Health related quality of life during treatment will be assessed at 4 weekly intervals and then every 8 weeks after end of treatment until progression. We cannot guarantee that participants will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who have limited treatment options available to them. It is hoped that pamiparib will be well tolerated and will improve outcomes for future patients, however there may be no clear benefit from participation in this study.
Interventions
Pamiparib is the study intervention in this trial.
Pamiparib will be administered in the form of capsules taken orally at a dose of 60 mg twice daily continuously until disease progression, unacceptable toxicity, participant withdrawal or at the discretion of the investigator.
Pamiparib may be reduced to 40mg twice daily if participants experience intolerable toxicity. If participants continue to experience intolerable toxicity, pamiparib dosage may be further reduced to 20mg twice daily. I
Pamiparib is the study intervention in this trial. Pamiparib will be administered in the form of capsules taken orally at a dose of 60 mg twice daily continuously until disease progression, unacceptable toxicity, participant withdrawal or at the discretion of the investigator. Pamiparib may be reduced to 40mg twice daily if participants experience intolerable toxicity. If participants continue to experience intolerable toxicity, pamiparib dosage may be further reduced to 20mg twice daily. If a third dose reduction is required, the participant should come off study treatment. Participants will be asked to return unused drug and empty drug containers at each return visit. The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each participant.
Sponsors
The University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria - participants from Pan cancer subprogram 1. Adults, aged 18 years and older, with pathologically confirmed high grade haematological malignancy of any myeloid subtype, including but not limited to AML, MDS and MPN or an earlier diagnosis of a poor prognosis cancer. 2. Confirmation of molecular eligibility by the molecular tumour board to have germline or somatic DNA repair pathway mutation (e.g. BRCA1/2, ATM, RAD1/2, PALB2), and/or BRCA mutational signature. 3. ECOG performance status 0-2. 4. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists; 5. Measurable disease assessed within 28 days prior to registration. Percentage bone marrow infiltration or circulating myeloid blast cells may be used as a surrogate for measurable disease. 6. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug): a. bone marrow function; platelets greater than or equal to 100 x 10^9/L, ANC greater than or equal to 1.5 x 10^9/L, and haemoglobin greater than or equal to 9g/dL (5.6mmol/L),; except where bone marrow function is reduced as a result of the underlying disease; b. liver function; ALT/AST less than or equal to 3 x ULN and total bilirubin less than or equal to 1.5xULN; patients with Gilberts syndrome less than or equal to 4 x ULN c. renal function; serum creatinine calculated GFR (glomerular filtration rate) greater than 30ml/min 7. Sufficient and accessible tissue (Bone marrow aspirate) less than 3 months old for exploratory objectives 8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments 9. Signed, written informed consent to participation in the specific treatment substudy. 10. Life expectancy of at least 12 weeks
Exclusion criteria
1. Previous treatment with a PARP inhibitor; 2. Known history of hypersensitivity or contraindication to pamiparib; 3. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s) as assessed by the treating physician; 4. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol; 5. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment: a. Radiation therapy, within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions; b. Immunotherapy within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment; c. Chemotherapy, biologic therapy, or hormonal therapy within 7 days or 5 half-lives of a drug prior to the first dose of study treatment or until recovery from previous therapy (whichever is longer); d. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 6. Administration of any investigational treatment within 28 days prior to receiving the first dose of pamiparib 7. Any unresolved toxicity (greater than CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy); 8. Known history of active tuberculosis 9. Receipt of live attenuated vaccination within 30 days prior to study entry 10. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception. 11. Has difficulty with or is unable to swallow oral medication, or has gastrointestinal disease that would limit the absorption of oral medication 12. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer 13. Eligible for participation in another MoST substudy based on identification of an actionable mutation. Patients who have previously participated in another MoST substudy may subsequently participate in this study, all other inclusion and exclusion criteria being satisfied. 14. Any of the following cardiovascular criteria: a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, within 28 days prior to registration b. Symptomatic pulmonary embolism within 28 days prior to registration c. Any history of acute myocardial infarction within 6 months prior to registration d. Any history of heart failure meeting New York Heart Association Classification III or IV within 6 months prior to registration e. Any event of ventricular arrhythmia greater than or equal to Grade 2 in severity within 6 months prior to registration f. Any history of cerebral vascular accident within 6 months prior to registration
Outcome results
None listed