Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer

NCT01037790 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 03909
• Study Type: interventional
• Target: 304
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Response Rates

  Response rates will be measured using the Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR) - Disappearance of all target lesions Partial Response (PR) - ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline Progressive Disease (PD) - ≥20% increase in the sum of the longest diameter of the target lesions compared with the smallest sum of the longest diameter recorded since treatment started OR The appearance of 1 or more new lesions Stable Disease (SD) - Neither PR or PD Not Evaluable (NE)

  10 years

Study Arms (5)

Arm 1 - Metastatic breast cancer

EXPERIMENTAL

Metastatic breast cancer PD-0332991 Given orally, 125 mg QD on a 21-day

Drug: PD-0332991

Arm 2 - Metastatic colorectal cancer that harbors the Kras or BRAF mutation

EXPERIMENTAL

Metastatic colorectal cancer that harbors the Kras or BRAF mutation PD-0332991 Given orally, 125 mg QD on a 21-day

Drug: PD-0332991

Arm 3 - Advanced or metastatic esophageal and/or gastric cancer

EXPERIMENTAL

Advanced or metastatic esophageal and/or gastric cancer PD-0332991 Given orally, 125 mg QD on a 21-day

Drug: PD-0332991

Arm 4 - Cisplatin-refractory, unresectable germ cell tumors

EXPERIMENTAL

Cisplatin-refractory, unresectable germ cell tumors PD-0332991 Given orally, 125 mg QD on a 21-day

Drug: PD-0332991

Arm 5 - CCND1amplification, CDK4/6mutation, CCND2amplification, OR other functional G1/S alterations

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 Given orally, 125 mg QD on a 21-day

Drug: PD-0332991

Interventions

PD-0332991 DRUG

Given orally, 125 mg QD on a 21-day

Also known as: Palbociclib

Arm 1 - Metastatic breast cancer; Arm 2 - Metastatic colorectal cancer that harbors the Kras or BRAF mutation; Arm 3 - Advanced or metastatic esophageal and/or gastric cancer; Arm 4 - Cisplatin-refractory, unresectable germ cell tumors; Arm 5 - CCND1amplification, CDK4/6mutation, CCND2amplification, OR other functional G1/S alterations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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:
• ongoing or active infection
• diabetes mellitus
• hypertension
• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Karasic TB, O'Hara MH, Teitelbaum UR, Damjanov N, Giantonio BJ, d'Entremont TS, Gallagher M, Zhang PJ, O'Dwyer PJ. Phase II Trial of Palbociclib in Patients with Advanced Esophageal or Gastric Cancer. Oncologist. 2020 Dec;25(12):e1864-e1868. doi: 10.1634/theoncologist.2020-0681. Epub 2020 Aug 8.

  PMID: 32692450 DERIVED

• 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.

  PMID: 32641862 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Teratoma; Breast Neoplasms, Male; Breast Neoplasms; Testicular Neoplasms; Melanoma

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms

Results Point of Contact

• Title: Jennifer Louie, Program Manager
• Organization: University of Pennsylvania

Jennifer.Louie2@pennmedicine.upenn.edu

267-414-6179

Study Officials

• Peter ODwyer

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2009
• First Posted: December 23, 2009
• Study Start: October 1, 2009
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: March 11, 2021
• Results First Posted: March 11, 2021

Record last verified: 2021-02

Locations

US (1)