Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
Condition: 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
MeSH terms: Breast Neoplasms; Melanoma; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Neoplasms, Germ Cell and Embryonal; Germinoma; Ovarian Neoplasms; Teratoma; Testicular Neoplasms; Breast Neoplasms, Male; Seminoma; Dermoid Cyst; Recurrence
Intervention: PD-0332991
Intervention description: Given orally, 125 mg QD on a 21-day
Intervention MeSH terms: Palbociclib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 304.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

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.