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PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER

NCT01037790

Description:

RATIONALE: PD 0332991 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and how well PD 0332991 works in treating patients with refractory solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Germ Cell Tumor
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER

Title

  • Brief Title: PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER
  • Official Title: Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
  • Clinical Trial IDs

    NCT ID: NCT01037790

    ORG ID: UPCC 03909

    NCI ID: NCI-2009-01467

    Trial Conditions

    Adult Solid Tumor

    Adenocarcinoma of the Colon

    Adenocarcinoma of the Rectum

    Adult Central Nervous System Germ Cell Tumor

    Adult Teratoma

    Benign Teratoma

    Estrogen Receptor-negative Breast Cancer

    Estrogen Receptor-positive Breast Cancer

    Familial Testicular Germ Cell Tumor

    HER2-negative Breast Cancer

    HER2-positive Breast Cancer

    Male Breast Cancer

    Ovarian Immature Teratoma

    Ovarian Mature Teratoma

    Ovarian Monodermal and Highly Specialized Teratoma

    Progesterone Receptor-negative Breast Cancer

    Progesterone Receptor-positive Breast Cancer

    Recurrent Breast Cancer

    Recurrent Colon Cancer

    Recurrent Extragonadal Germ Cell Tumor

    Recurrent Extragonadal Non-seminomatous Germ Cell Tumor

    Recurrent Extragonadal Seminoma

    Recurrent Malignant Testicular Germ Cell Tumor

    Recurrent Melanoma

    Recurrent Ovarian Germ Cell Tumor

    Recurrent Rectal Cancer

    Stage III Extragonadal Non-seminomatous Germ Cell Tumor

    Stage III Extragonadal Seminoma

    Stage III Malignant Testicular Germ Cell Tumor

    Stage III Ovarian Germ Cell Tumor

    Stage IV Breast Cancer

    Stage IV Colon Cancer

    Stage IV Extragonadal Non-seminomatous Germ Cell Tumor

    Stage IV Extragonadal Seminoma

    Stage IV Melanoma

    Stage IV Ovarian Germ Cell Tumor

    Stage IV Rectal Cancer

    Testicular Immature Teratoma

    Testicular Mature Teratoma

    Trial Interventions

    Drug Synonyms Arms
    PD-0332991 Arm 1, Arm 2, Arm 3, Arm 4, Arm 5

    Trial Purpose

    RATIONALE: PD 0332991 may stop the growth of tumor cells by blocking some of the enzymes
    needed for cell growth.

    PURPOSE: This phase II trial is studying the side effects and how well PD 0332991 works in
    treating patients with refractory solid tumors.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the response rates following treatment with PD 0332991 in the following
    malignancies: 1) Metastatic breast cancer, 2) Metastatic colorectal cancer, 3) Metastatic
    melanoma with CDK4 mutation or amplification, or 4) Cisplatin-refractory, unresectable germ
    cell tumors.

    II. To evaluate the safety and tolerability of PD 0332991 administered to subjects with
    refractory solid tumors.

    SECONDARY OBJECTIVES:

    I. To assess the pharmacodynamic effects of PD0332991 on tumor and non-tumor tissue.

    II. To investigate the relationship between selected biomarkers, PK and/or efficacy and
    safety outcomes.

    III. To estimate the population pharmacokinetic for PD 0332991 and to correlate PK with
    efficacy outcomes.

    IV: To perform a Phase II evaluation of PD 0332991 in a population defined as potential
    responders on the basis of CCND1 gene amplification.

    OUTLINE:

    Patients receive oral PD 0332991 once daily on days 1-21. Treatment repeats every 28 days
    for up to 12 courses in the absence of unacceptable toxicity or disease progression.

    Trial Arms

    Name Type Description Interventions
    Arm 1 Experimental Metastatic breast cancer PD-0332991
    Arm 2 Experimental Metastatic colorectal cancer that harbors the Kras or BRAF mutation PD-0332991
    Arm 3 Experimental Advanced or metastatic esophageal and/or gastric cancer PD-0332991
    Arm 4 Experimental Cisplatin-refractory, unresectable germ cell tumors PD-0332991
    Arm 5 Experimental Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation , CCND2 amplification OR any other functional alteration at the G1/S checkpoint. PD-0332991

    Eligibility Criteria

    Inclusion Criteria:

    - Disease Characteristics:

    All Subjects: All subjects treated under this protocol will have histologically documented
    cancer of one of the following types:

    A. Metastatic breast cancer (7 triple negative, 23 ER+ after the first 15 patients are
    enrolled on the non-CCND1cohort; in addition 10 HER2+ for combination trastuzumab and
    PD0332991 therapy) up to 55 total enrollment slots B. Metastatic colorectal cancer that
    harbors the Kras or BRAF mutation (15-30 enrollment slots) C. Advanced or metastatic
    esophageal and/or gastric cancer (15-30 enrollment slots) D. Cisplatin-refractory,
    unresectable germ cell tumors (15-30 enrollment slots) E. Any tumor type if tissue tests
    positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other
    functional alteration at the G1/S checkpoint. (15-30 enrollment slots)

    - Biopsy Requirements: For Subjects with accessible disease amenable to biopsy: A biopsy
    will be obtained pre-treatment and in during cycle 1 (while patient is receiving drug) for
    molecular markers of the cell cycle, and its inhibition.

    - Subjects will be > 18 years old

    - The subject has disease that is assessable by tumor marker, physical, or radiologic
    means.

    - The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0
    or 1.

    - The subject has adequate organ function, defined as follows A. Bilirubin 1.5 x the
    upper limit of normal (ULN) B. Serum creatinine 1.5 x UNL or calculated creatinine
    clearance 60 mL/min, and C. For subjects without liver metastases: alanine
    aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 x ULN D. For
    subjects with liver metastases: alanine aminotransferase (ALT) and aspartate
    aminotransferase 5 x ULN

    - All tumors must test positive for Rb expression except:

    A. ER positive metastatic breast tumors (data now shows all to be Rb positive.) B. Any
    tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2
    amplification OR any other functional alteration at the G1/S checkpoint.

    - The subject has adequate marrow function, defined as follows: A. Absolute neutrophil
    count (ANC) >1500/mm3 B. Platelets >100,000/mm3, and C. Hemoglobin > 9 g/dL

    - The subject is capable of understanding and complying with the protocol requirements
    and has signed the informed consent document.

    - Sexually active subjects (male and female) must use accepted methods of contraception
    during the course of the study and for 3 months after the last dose of protocol
    drug(s).

    - Female subjects of childbearing potential must have a negative pregnancy test at
    screening. Females of childbearing potential are defined as sexually mature women
    without prior hysterectomy or who have had any evidence of menses in the past 12
    months.

    - However, women who have been amenorrheic for 12 or more months are still considered
    to be of childbearing potential if the amenorrhea is possibly due to prior
    chemotherapy, antiestrogens, or ovarian suppression.

    Exclusion Criteria

    - The subject has received cytotoxic chemotherapy (including investigational cytotoxic
    chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before
    the first dose of PD 0332991. . Patients with HER2-overexpressing tumors may receive
    trastuzumab up to the date of starting therapy, and may continue to receive
    trastuzumab while receiving PD0332991.

    - The subject has received any other type of investigational agent within 28 days
    before the first dose of study treatment.

    - The subject has not recovered from clinically-meaningful toxicity due to prior
    therapy (i.e., back to baseline or Grade 1), with the exception of neurotoxicity
    and alopecia.

    - The subject has untreated or uncontrolled brain metastases or evidence of
    leptomeningeal involvement of disease unless the subject has a teratoma in which case
    s/he may be eligible if all other eligibility criteria are met

    - The subject has uncontrolled intercurrent illness including, but not limited to:

    1. ongoing or active infection

    2. diabetes mellitus

    3. hypertension

    4. symptomatic congestive heart failure, unstable angina pectoris, stroke or
    myocardial infarction within 3 months

    - The subject has a baseline corrected QT interval (QTc) > 470 ms.

    - The subject is pregnant or breastfeeding.

    - The subject is known to be positive for the human immunodeficiency virus (HIV). Note:

    baseline HIV screening is not required

    - The subject is unable or unwilling to abide by the study protocol or cooperate fully
    with the investigator or designee.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response rates

    Safety and tolerability

    Secondary Outcome Measures

    Pharmacodynamic effects on tumor and non-tumor tissue

    Relationship between selected biomarkers, pharmacokinetics, and/or efficacy and safety outcomes

    Population pharmacokinetic for PD 0332991 and correlation with efficacy outcomes

    Trial Keywords