PD0332991 in Patients With Advanced or Metastatic Liposarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01209598
First received: September 24, 2010
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to find out what effects, good and/or bad, PD0332991 has on the patient and on the liposarcoma.

PD0332991 is an investigational drug. An investigational drug is a medication that has not been approved for marketing by the Food and Drug Administration (FDA). PD0332991 blocks a protein called CDK4 which is part of a pathway in liposarcoma cells that is over-active. The investigators hope that blocking CDK4 will shut down this pathway in the liposarcoma cells and stop tumors from growing. PD0332991 is an oral medication.


Condition Intervention Phase
Sarcoma
Liposarcoma
Drug: PD0332991
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: A Phase II Study Of PD0332991 in Patients With Advanced or Metastatic Liposarcoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • to determine the proportion of patients with advanced/metastatic liposarcoma who are progression-free at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    PFS, defined as RECIST 1.1 CR + PR + SD) when treated with PD0332991


Secondary Outcome Measures:
  • Overall response rate (defined as CR + PR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinical benefit rate (CR + PR + SD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 86
Study Start Date: September 2010
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PD0332991
This is a phase II study of PD0332991 in patients with advanced / metastatic liposarcoma. A one-stage design is used to determine whether patients treated with PD0332991 achieved a PFS rate of ≥ 40% at 12 weeks.
Drug: PD0332991

Treatment will consist of either:

Schedule 2/1: PD0332991 200mg given once daily by mouth for 14 consecutive days, followed by 7 days of rest. A cycle will be defined as 21 days.

Schedule 3/1: PD0332991 125mg given once daily by mouth for 21 consecutive days, followed by 7 days of rest. A cycle will be defined as 28 days. Following the positive results of the study, a new Expansion Cohort has been added to permit enrollment of up to 20 additional patients.

Expansion Cohort: Dosed as per Schedule 3/1


  Eligibility

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

Inclusion Criteria:

  • A diagnosis of liposarcoma confirmed at MSKCC. Because myxoid / round cell liposarcoma does not have significant CDK4 amplification, patients with this subtype are not eligible.
  • Metastatic and/or locally advanced or locally recurrent disease that is not surgically resectable, with evidence of disease progression, either clinically or radiographically, as determined by the investigator
  • All patients must have measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >10 mm when measured by CT, MRI or caliper measurement by clinical exam; or >20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.
  • A minimum of 1 prior systemic regimen for recurrent/metastatic disease. Note: This requirement does not apply to patients enrolled in the Expansion Cohort. The last dose of systemic therapy (include targeted therapies) must have been given at least 2 weeks prior to initiation of therapy. Patients receiving BCNU or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy.
  • Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months are eligible.
  • Age > or = 18 years.
  • ECOG performance status 0 or 1.
  • Adequate organ and marrow function as defined below (ULN indicates institutional upper limit of normal):

Absolute neutrophil count ≥ 1.5x109/L Hemoglobin ≥ 9.0 g/dL WBC ≥ 3.0x109/L Platelets ≥ 100x109/L Total bilirubin ≤ 1.5 x ULN except for patients with known Gilbert syndrome AST(SGOT)/ALT(SGPT) ≤ 3 x institutional ULN Serum creatinine ≤ 1.5 x ULN or Creatinine Clearance > 50 mL/min (calculated by Cockcroft-Gault method)QTc interval ≤ 470 msec

  • Patients must not have current evidence of another malignancy that requires treatment.
  • The effects of PD0332991 on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence). Women must not breast feed while on study.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Ability to swallow intact PD0332991 capsules.
  • Patients‟ tumors must express Rb, as assessed using an historical biopsy sample if available or a newly obtained tumor sample. Samples must demonstrate ≥1+ staining for Rb. Patients' tumors must also have evidence of CDK4 amplification by FISH. Note: This does not apply to patients enrolled in the Expansion Cohort.

Exclusion Criteria:

  • Patients who have not recovered from adverse events of prior therapy to ≤ NCI CTCAEv4.0 Grade 1.
  • Patients receiving any other investigational agents.
  • Patients who have received prior treatment with a selective CDK4 inhibitor
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD0332991.
  • Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including HIV, active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (specifically, atrial fibrillation or ventricular dysrhythmias except ventricular premature contractions), or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women and women who are breast-feeding.
  • Patients with a history of long-QT syndrome or documented family history of long-QT syndrome. Patients who must remain on drugs that prolong the QT interval.
  • PD0332991 is a substrate of CYP3A. Caution should be exercised when dosing PD0332991 concurrently with CYP3A inducers or inhibitors. Furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk. A list of CYP3A4 substrates, inducers and/or inhibitors is provided in Appendix B. The following medications with strong potential for interaction are not allowed: indinavir nelfinavir ritonavir clarithromycin itraconazole ketoconazole nefazodone saquinavir telithromycin carbamazepine phenobarbital phenytoin pioglitazone rifabutin rifampin St. John's wort Troglitazone
  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: NCT01209598

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Pfizer
Investigators
Principal Investigator: Mark Dickson, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01209598     History of Changes
Other Study ID Numbers: 10-094
Study First Received: September 24, 2010
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
soft tissue
PD0332991
10-094

Additional relevant MeSH terms:
Liposarcoma
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma

ClinicalTrials.gov processed this record on September 16, 2014