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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2015 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01037790
First received: December 10, 2009
Last updated: December 7, 2015
Last verified: December 2015
  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.


Condition Intervention Phase
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
Drug: PD-0332991
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • Response rates [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacodynamic effects on tumor and non-tumor tissue [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Relationship between selected biomarkers, pharmacokinetics, and/or efficacy and safety outcomes [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Population pharmacokinetic for PD 0332991 and correlation with efficacy outcomes [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 205
Study Start Date: October 2009
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Metastatic breast cancer
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other: pharmacological study
Correlative study
Other Name: pharmacological studies
Experimental: Arm 2
Metastatic colorectal cancer that harbors the Kras or BRAF mutation
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other: pharmacological study
Correlative study
Other Name: pharmacological studies
Experimental: Arm 3
Advanced or metastatic esophageal and/or gastric cancer
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other: pharmacological study
Correlative study
Other Name: pharmacological studies
Experimental: Arm 4
Cisplatin-refractory, unresectable germ cell tumors
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other: pharmacological study
Correlative study
Other Name: pharmacological studies
Experimental: Arm 5
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.
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other: pharmacological study
Correlative study
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037790

Contacts
Contact: Peter O Dwyer, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramson Cancer Center of The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Peter ODwyer    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Peter ODwyer         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Peter ODwyer Abramson Cancer Center of the University of Pennsylvania
  More Information

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01037790     History of Changes
Other Study ID Numbers: UPCC 03909  NCI-2009-01467 
Study First Received: December 10, 2009
Last Updated: December 7, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Testicular Neoplasms
Adenocarcinoma
Breast Neoplasms
Breast Neoplasms, Male
Dermoid Cyst
Germinoma
Melanoma
Neoplasms, Germ Cell and Embryonal
Ovarian Neoplasms
Rectal Neoplasms
Seminoma
Teratoma
Adnexal Diseases
Breast Diseases
Carcinoma
Colorectal Neoplasms
Cysts
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Female
Genital Diseases, Male
Genital Neoplasms, Female
Genital Neoplasms, Male
Gonadal Disorders
Intestinal Diseases
Intestinal Neoplasms

ClinicalTrials.gov processed this record on May 23, 2016