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 ACTRN12616000908437. This substudy will evaluate the activity of palbociclib in patients with advanced cancers and tumours with mutations in components of the Rb-pathway. Who is it for? All participants in this study must have completed screening as part of the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437), and been identified as having tumours carrying somatic mutations in the Rb-pathway including amplification or activating mutations in CCND1, CCND2, CCND3 or CDK4, or loss of function mutations in CDKN2A. They must also be able to swallow capsules. Study details All participants in this study will take the drug, palbociclib, orally once daily at a dose of 125mg/day for days 1-21, every 28 day cycle (3 weeks on, 1 week off). Treatment will continue until progression, unacceptable toxicity or withdrawal. All participants will undergo assessments at 8 weekly intervals or as clinically indicated in order to evaluate tumour response, safety and tolerability of treatment, health related quality of life during treatment, and overall survival. We cannot guarantee that patients will receive any benefits from this study. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that palbociclib will be well tolerated and will improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
Palbociclib will be administered orally once daily at a dose of 125mg/day (one capsule) for days 1-21, every 28 day cycle (3 weeks on, 1 week off).
Palbociclib will be administered continuously until documented disease progression, intolerable toxicity or withdrawal for another reason.
The Pharmacy Department at participating institutions will maintain a record of drugs dispensed for each patient and subsequent returns.
Sponsors
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
To be eligible for treatment in a substudy, patients must continue to meet all of the inclusion criteria and none of the exclusion criteria specified for entry into molecular screening at the time of registration to a treatment substudy. In addition, they must meet all the inclusion criteria and none of the exclusion criteria in the substudy addendum at the time of registration. 1. Confirmation of molecular eligibility by the molecular tumour board; 2. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists; 3. Clinical or radiological progression on or following last anticancer therapy; 4. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug): 5. Meet any additional inclusion criteria specified in the relevant substudy addendum; 6. Signed, written informed consent to participation in the specific treatment substudy. Inclusion Criteria specific to this sub-study : 1. Subjects with tumours carrying somatic mutations in the Rb-pathway including amplification or activating mutations in CCND1, CCND2, CCND3 or CDK4, or loss of function mutations in CDKN2A; 2. Able to swallow capsules.
Exclusion criteria
Exclusion criteria will include those relevant for screening but also include: 1. Contraindications to investigational product, as listed in the substudy addendum and outlined in the Investigator Brochure appended to each substudy module; 2. Known history of hypersensitivity to active or inactive components of investigational product; 3. Previous treatment with the same agent or same class of agent; 4. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment: o Radiation therapy, surgery or tumour embolization 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; o Immunotherapy within 28 days prior to the first dose of study treatment; o Chemotherapy, biologic therapy, investigation therapy or hormonal therapy within 30 days or 5 half-lives of a drug (whichever is longer), prior to the first dose of study treatment; 5. Administration of any non-oncologic investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment; 6. Any additional exclusion criteria specified in the relevant substudy addendum. Exclusion Criteria specific to this sub-study: 1. Subjects with breast cancer, mantle cell lymphoma, myeloma, or germ cell tumours; 2. Patients with steroid-responsive tumours must be on a stable dose of dexamethasone for a minimum of 14 days prior to registration 3. Contraindications to palbociclib, including known hypersensitivity to any of the components of palbociclib; 4. Prior treatment with a CDK inhibitor.
Outcome results
None listed