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

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ClinicalTrials.gov Identifier: NCT01037790
Recruitment Status : Completed
First Posted : December 23, 2009
Last Update Posted : April 7, 2020
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 10, 2009
First Posted Date  ICMJE December 23, 2009
Last Update Posted Date April 7, 2020
Study Start Date  ICMJE October 2009
Actual Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2015)
  • Response rates [ Time Frame: 5 years ]
  • Safety and tolerability [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2009)
  • Response rates
  • Safety and tolerability
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2015)
  • Pharmacodynamic effects on tumor and non-tumor tissue [ Time Frame: 5 years ]
  • Relationship between selected biomarkers, pharmacokinetics, and/or efficacy and safety outcomes [ Time Frame: 5 years ]
  • Population pharmacokinetic for PD 0332991 and correlation with efficacy outcomes [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2009)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER
Official Title  ICMJE Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
Brief 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: PD-0332991
    Given orally, 125 mg QD on a 21-day
  • Other: pharmacological study
    Correlative study
    Other Name: pharmacological studies
Study Arms  ICMJE
  • Experimental: Arm 1
    Metastatic breast cancer
    Interventions:
    • Drug: PD-0332991
    • Other: pharmacological study
  • Experimental: Arm 2
    Metastatic colorectal cancer that harbors the Kras or BRAF mutation
    Interventions:
    • Drug: PD-0332991
    • Other: pharmacological study
  • Experimental: Arm 3
    Advanced or metastatic esophageal and/or gastric cancer
    Interventions:
    • Drug: PD-0332991
    • Other: pharmacological study
  • Experimental: Arm 4
    Cisplatin-refractory, unresectable germ cell tumors
    Interventions:
    • Drug: PD-0332991
    • Other: pharmacological study
  • 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.
    Interventions:
    • Drug: PD-0332991
    • Other: pharmacological study
Publications * McAndrew NP, Dickson MA, Clark AS, Troxel AB, O'Hara MH, Colameco C, Gallager M, Gramlich K, Zafman K, Vaughn D, Schwartz GK, O'Dwyer PJ, DeMichele A. Early treatment-related neutropenia predicts response to palbociclib. Br J Cancer. 2020 Sep;123(6):912-918. doi: 10.1038/s41416-020-0967-7. Epub 2020 Jul 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2020)
304
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2009)
120
Actual Study Completion Date  ICMJE October 2019
Actual Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01037790
Other Study ID Numbers  ICMJE UPCC 03909
NCI-2009-01467
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Abramson Cancer Center of the University of Pennsylvania
Study Sponsor  ICMJE Abramson Cancer Center of the University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter ODwyer Abramson Cancer Center of the University of Pennsylvania
PRS Account Abramson Cancer Center of the University of Pennsylvania
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP