Trial Summary:

Inhibition of cyclin-dependent kinases (CDK) 4 and 6 blocks DNA synthesis by prohibiting progression of the cell cycle from G1 to S phase. Specifically, in complex with cyclin D, CDK4 phosphorylates retinoblastoma protein (Rb) and drives cell‐cycle progression. Cell cycle control through CDK inhibition has emerged as an attractive option in the development of targeted cancer therapy. Some tumours display biologic features suggesting particular dependence on this interaction. Of specific interest are tumours with amplified D‐type cyclins or CDK4 or inactivation of CDKN2A.

The aim of substudy 1 is to assess the clinical activity of palbociclib in patients with with advanced cancer and somatic mutations identified through molecular screening in components of the Rb pathway upstream of Rb itself. Genetic alterations include amplification or activating mutations in CCND1, CCND2, CCND3 or CDK4, or loss of function mutations in CDKN2A. To be eligible this trial, patients must continue to meet all of the inclusion criteria and none of the exclusion criteria specified in the MoST framework protocol (sections 5.3-5.8) and, in addition, meet all the inclusion criteria and none of the exclusion criteria below at the time of registration. Patients with breast cancer, mantle cell lymphoma, myeloma, or germ cell tumours are the subject of ongoing studies elsewhere and will be excluded from this study.

Supported By:

OHMR, CGMP, Pfizer

Eligibility:

 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;

Registration ID:

ACTRN12616000931471

Participation:

National

Status:

Closed

Activation Date:

7/11/2016

Chairs:

Katrin Sjoquist

Contact:

most.study@sydney.edu.au