A Study Of Oral Palbociclib (PD-0332991), A CDK4/6 Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-Line Treatment Of Postmenopausal Japanese Patients With ER (+) HER2 (-) Advanced Breast Cancer
Condition: Neoplasms; Breast Neoplasms
MeSH terms: Breast Neoplasms; Neoplasms
Intervention: PD-0332991; PD-0332991; letrozole; PD-0332991; letrozole
Intervention description: PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.; PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.; Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.; PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.; Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.
Intervention MeSH terms: Letrozole; Palbociclib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Phase 1/2; PD-0332991; palbociclib; Cyclin Dependent Kinase 4/6 inhibitor; Japanese; solid tumors; breast cancer; A5481010

Summary:

      This study is comprised of two portions: a Phase 1 portion and a Phase 2 portion. The Phase 1
      portion is a single-country, non-randomized, open label, clinical trial which will evaluate
      the safety, tolerability, preliminary efficacy, and PK profile of PD-0332991 as a single
      agent in Japanese patients with advanced solid tumors, and PD-0332991 in combination with
      letrozole in the first-line treatment of Japanese patients with ER(+) HER2(-) ABC. The Phase
      2 portion is a single-country, non-randomized, open-label, single-cohort, multi-center
      clinical trial to evaluate the efficacy and safety of PD-0332991 in combination with
      letrozole for the first-line treatment of postmenopausal Japanese patients with ER(+) HER2(-)
      ABC.
    

Eligibility criteria:

        Inclusion Criteria:

        Phase 1

          -  In Part 1, advanced solid tumor (except SCLC or retinoblastoma) proven histologically
             or cytologically at original diagnosis, that is refractory to standard therapy or for
             whom no standard of care therapy is available.

          -  In Part 2 and Phase 2, post menopausal women with proven diagnosis of ER-positive,
             HER2-negative adenocarcinoma of the breast with evidence of locoregionally recurrent
             or metastatic disease (including bone only disease) not amenable to resection or
             radiation therapy with curative intent and for whom chemotherapy is not clinically
             indicated.

          -  Adequate blood cell counts, kidney function and liver function and and Eastern
             Cooperative Oncology Group [ECOG] score of 0 or 1.

          -  Resolved acute effects of any prior therapy to baseline severity or Grade ≤1

        Phase 2

          -  Adult women (≥ 20 years of age) with proven diagnosis of adenocarcinoma of the breast
             with evidence of locoregionally recurrent or metastatic disease not amenable to
             resection or radiation therapy with curative intent and for whom chemotherapy is not
             clinically indicated.

          -  Documentation of histologically or cytologically confirmed diagnosis of ER(+) breast
             cancer based on local laboratory results.

          -  Adequate blood cell counts, kidney function and liver function and and Eastern
             Cooperative Oncology Group [ECOG] score of 0 to 2.

        Exclusion Criteria:

        Phase 1

          -  Active uncontrolled or symptomatic CNS metastases.

          -  Uncontrolled infection, unstable or sever intercurrent medical condition, or current
             drug or alcohol abuse

          -  Active or unstable cardiac disease or history of heart attack within 6 months

        Phase 2

          -  HER2 positive tumor based on local laboratory results utilizing one of the sponsor
             approved assays.

          -  Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
             leptomeningeal disease.

          -  Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie,
             anastrozole or letrozole) with disease recurrence while on or within 12 months of
             completing treatment.