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PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma

Primary Purpose

Sarcoma, Liposarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Palbociclib 200mg
Palbociclib 125mg
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring soft tissue, Palbociclib (PD0332991), 10-094

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 Palbociclib 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 Palbociclib 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 Palbociclib.
  • 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.
  • Palbociclib is a substrate of CYP3A. Caution should be exercised when dosing Palbociclib 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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Palbociclib 200mg

Palbociclib 125mg

Arm Description

This is a phase II study of Palbociclib in patients with advanced / metastatic liposarcoma. A one-stage design is used to determine whether patients treated with Palbociclib achieved a PFS rate of ≥ 40% at 12 weeks.

This is a phase II study of Palbociclib in patients with advanced / metastatic liposarcoma. A one-stage design is used to determine whether patients treated with Palbociclib achieved a PFS rate of ≥ 40% at 12 weeks.

Outcomes

Primary Outcome Measures

Progression Free Survival at 12 Weeks
PFS, defined as RECIST 1.1 (CR + PR + SD) when treated with Palbociclib

Secondary Outcome Measures

Best Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Full Information

First Posted
September 24, 2010
Last Updated
October 5, 2017
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01209598
Brief Title
PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma
Official Title
A Phase II Study Of PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
September 23, 2010 (Actual)
Primary Completion Date
October 25, 2016 (Actual)
Study Completion Date
October 25, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to find out what effects, good and/or bad, Palbociclib (Ibrance) (formerly known as PD0332991) has on the patient and on the liposarcoma. Palbociclib is an investigational drug. An investigational drug is a medication that has not been approved for marketing by the Food and Drug Administration (FDA). Palbociclib 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. Palbociclib is an oral medication.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Liposarcoma
Keywords
soft tissue, Palbociclib (PD0332991), 10-094

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Palbociclib 200mg
Arm Type
Experimental
Arm Description
This is a phase II study of Palbociclib in patients with advanced / metastatic liposarcoma. A one-stage design is used to determine whether patients treated with Palbociclib achieved a PFS rate of ≥ 40% at 12 weeks.
Arm Title
Palbociclib 125mg
Arm Type
Experimental
Arm Description
This is a phase II study of Palbociclib in patients with advanced / metastatic liposarcoma. A one-stage design is used to determine whether patients treated with Palbociclib achieved a PFS rate of ≥ 40% at 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Palbociclib 200mg
Intervention Description
Schedule 2/1: Palbociclib 200mg given once daily by mouth for 14 consecutive days, followed by 7 days of rest. A cycle will be defined as 21 days.
Intervention Type
Drug
Intervention Name(s)
Palbociclib 125mg
Intervention Description
Schedule 3/1: Palbociclib 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. Capsules should be taken with food.
Primary Outcome Measure Information:
Title
Progression Free Survival at 12 Weeks
Description
PFS, defined as RECIST 1.1 (CR + PR + SD) when treated with Palbociclib
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Best Response
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 Palbociclib 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 Palbociclib 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 Palbociclib. 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. Palbociclib is a substrate of CYP3A. Caution should be exercised when dosing Palbociclib 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Dickson, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32641862
Citation
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.
Results Reference
derived
PubMed Identifier
27124835
Citation
Dickson MA, Schwartz GK, Keohan ML, D'Angelo SP, Gounder MM, Chi P, Antonescu CR, Landa J, Qin LX, Crago AM, Singer S, Koff A, Tap WD. Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial. JAMA Oncol. 2016 Jul 1;2(7):937-40. doi: 10.1001/jamaoncol.2016.0264.
Results Reference
derived
PubMed Identifier
23569312
Citation
Dickson MA, Tap WD, Keohan ML, D'Angelo SP, Gounder MM, Antonescu CR, Landa J, Qin LX, Rathbone DD, Condy MM, Ustoyev Y, Crago AM, Singer S, Schwartz GK. Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. J Clin Oncol. 2013 Jun 1;31(16):2024-8. doi: 10.1200/JCO.2012.46.5476. Epub 2013 Apr 8.
Results Reference
derived
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan-Kettering Cancer Center

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PD0332991 (Palbociclib) in Patients With Advanced or Metastatic Liposarcoma

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