Letrozole plus Oral CDK4/6 inhibitor in Advanced Breast Cancer

• Research type

  Research Study

• Full title

  Phase 1/2, open-label, randomised study of the safety efficacy, and pharmacokinetics of Letrozole plus PD 0332991 (oral CDK 4/6 inhibitor) and Letrozole sinble agent for the first-line treatment of ER positive, HER2 negative advance breast cancer in post menopausal women

• IRAS ID

  74458

• Contact name

  Catherine Harper-Wynne

• Sponsor organisation

  Pfizer Inc. 235 East 42nd Street, New York, NY 10017

• Eudract number

  2008-002392-27

• ISRCTN Number

  No number provided

• Clinicaltrials.gov Identifier

  No number provided

• Research summary

  The protocol includes both phase 1 and 2 information. This initial study comprised of a limited Phase 1 portion, this is now complete with 12 patients enrolled. The Phase 2 portion has been divided into 2 parts; part1 and 2. Phase 2 part 1 is also complete with 60 patients enrolled. This application to IRAS is for the Phase 2 part 2 study.The research is looking at improving the treatment of patients with Advanced Breast Cancer (ABC) which cannot be treated with surgery but that's sensitive to hormonal treatment. The medical need remains high in this population with as progression free survival is less than 1 year and overall survival is approximately 3 years. Letrozole is first line treatment for post menopausal women with receptor positive ABC. PD0332991-(Oral Cylin-Dependent Kinase (CDK) 4/6 inhibitor) works by blocking growth signals in breast cancer cells. The study is designed to assess the activity of the combination of letrozole plus PD 0332991 to determine if the effects are positive and further development of the combination in the biomarker-positive patient population is warranted. Patients will be screened for biomarker positive status to confirm they are eligible. A stored tumor sample from the original surgery will be tested to demonstrate that there is an increase in a gene cyclin D1 (CCND1) and/or loss of p16/INK4A/CDKN2A (hereafter referred to as p16). There is a mandatory molecular profiling component aimed at assessing the relationship between antitumour activity and expression of cell cycle- and aromatase-related proteins in tumor tissue and blood. Subject to IRB/IEC approval this study will include an additional research component involving collection of biological samples for anonymous exploratory gene mutation analysis. The Molecular Profiling Supplement to this protocol provides details of this additional research. Patients can take part in the study even if they do not choose to take part in optional sample banking component.

• REC name

  London - Brighton & Sussex Research Ethics Committee

• REC reference

  11/LO/1341

• Date of REC Opinion

  27 Oct 2011

• REC opinion

  Further Information Favourable Opinion