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Palbociclib In Progressive Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02896335
Recruitment Status : Recruiting
First Posted : September 12, 2016
Last Update Posted : September 7, 2020
Information provided by (Responsible Party):
Priscilla Brastianos, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE August 30, 2016
First Posted Date  ICMJE September 12, 2016
Last Update Posted Date September 7, 2020
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
Clinical Benefit Rate (Intracranial) [ Time Frame: 8 Weeks ]
Simon two-stage design comparing the proportion of intracranial responders (as defined by CR, PR or SD) under a null hypothesis response rate of 10% against an alternative of 30%.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
  • Clinical Benefit Rate (Extracranial) [ Time Frame: 8 Weeks ]
  • Intracranial disease progression rate [ Time Frame: Time from registration to the earlier of progression or death due to any cause. Patients will be followed for a maximum of 2 years after End-of-Treatment visit. ]
  • Extracranial disease progression rate [ Time Frame: Time from registration to the earlier of progression or death due to any cause. Patients will be followed for a maximum of 2 years after End-of-Treatment visit. ]
  • Overall Survival Rate [ Time Frame: registration to death due to any cause, or censored at date last known alive. Patients will be followed for a maximum of 2 years after End-of-Treatment visit. ]
    Kaplan-Meier estimates of overall survival will be presented with 90% confidence intervals estimated using log(-log(survival)) methodology
  • Number of Participants with Grade 3 or more hematologic toxicity; grade 3 or more neurologic toxicity [ Time Frame: 24 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Palbociclib In Progressive Brain Metastases
Official Title  ICMJE A Phase 2 Study of Palbociclib in Progressive Brain Metastases Harboring Alterations in the CDK Pathway
Brief Summary

This research study is studying palbociclib as a possible treatment for recurrent brain metastases.

- Pfizer, a pharmaceutical company, is supporting this research study by providing the study drug as well as funding for research activities

Detailed Description
  • This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
  • This is a study designed to evaluate the efficacy and safety of palbociclib in recurrent brain metastases. Palbociclib is being studied for use in the treatment of a broad range of cancers. This type of drug inhibits cell growth in the cells called cyclin-dependent kinases which promote tumor cell proliferation.
  • The FDA (the U.S. Food and Drug Administration) has not approved palbociclib for participants specific disease but it has been approved for other uses
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Malignant Neoplasm to Brain
Intervention  ICMJE Drug: Palbociclib
Other Name: Ibrance
Study Arms  ICMJE Experimental: Palbociclib

Description Patients who fulfill eligibility criteria will be entered into the trial to receive Palbociclib

After the screening procedures confirm participation in the research study:

  • Palbociclib- Fixed Dose, daily for 21 days per cycle.
  • The participant will be requested to maintain a medication diary of each dose of medication. The medication diary will be returned to clinic staff at the end of each cycle.
Intervention: Drug: Palbociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2016)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2024
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed disease from any solid tumor
  • Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm .
  • Participants must have progressive CNS lesions, as defined by one of the following:

    • Patients may have multiple progressive CNS lesions, some of which have been treated by SRS or surgery. Patients are eligible if they have one or more un-treated (by surgery or SRS) progressive lesions that is measurable.
    • Patients have measurable residual or progressive lesions after surgery.
    • Patients who have had prior WBRT and/or SRS are eligible but there needs to be unequivocal evidence of progression of at least one lesion treated by radiation (e.g. tissue diagnosis). Biopsy can be considered for definitive diagnosis.
    • Patients who have previously been treated with systemic therapy for CNS metastases are eligible.
  • Age ≥ 18 years. The toxicity of palbociclib in children is unknown.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Participants must have normal organ and marrow function as defined below:

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • hemoglobin >9g/dL
    • total bilirubin ≤ 1.5 x institutional upper limit of normal

      --- OR

    • > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range.
    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
    • creatinine within normal institutional limits

      --- OR

    • creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
    • baseline QTc <480ms
  • The effects of palbociclib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of palbociclib administration.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Tissue from a prior craniotomy or biopsy for genetic sequencing (at least one FFPE block or 15 unstained slides). Patients previously assessed for genetic sequencing who meet requirements of section 9.2.1 do not need to have additional tissue available for prospective genetic sequencing.
  • Presence of alteration in CDK pathway (amplifications in CDK4, CDK6, CCND1, CCND2, CCND3 or CCNE1 or loss of CDKN2A)
  • Patients with progressive extracranial disease will not be excluded.
  • Stable corticosteroids for at least 7 days

Exclusion Criteria:

  • Prior treatment with CDK4/6 inhibitor
  • Participants who have had chemotherapy, immunotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
  • Participants who are receiving any other investigational agents
  • Participants who are receiving other concurrent chemotherapies or immunotherapies for their cancer (except for patients who will receive letrozole, anastrozole, exemestane, tamoxifen, fulvestrant, trastuzumab, bisphosphonates, or ovarian suppression therapy)
  • Leptomeningeal involvement of cancer
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib (including abemaciclib)
  • Participants receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A isoenzymes are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in Appendix C, and can also be found within section 5.4. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with palbociclib, breastfeeding should be discontinued if the mother is treated with palbociclib.
  • HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with palbociclib. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Current use of drugs that are known to prolong the QT interval (See Appendix C)
  • Unable to undergo MRI scans.
  • QTc>480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QTc prolongation, or Torsade de Pointes (TdP).
  • Uncontrolled electrolyte disorders that can compound the effects of QTc-prolonging drug (eg. hypocalcemia, hypokalemia, hypomagnesemia
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: Priscilla Brastianos, MD 617-724-8770
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02896335
Other Study ID Numbers  ICMJE 16-254
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Priscilla Brastianos, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Priscilla Brastianos, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date September 2020

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