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Palbociclib In Progressive Brain Metastases

This study is currently recruiting participants.
Verified August 2017 by Priscilla Brastianos, Massachusetts General Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02896335
First Posted: September 12, 2016
Last Update Posted: August 29, 2017
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.
Collaborator:
Pfizer
Information provided by (Responsible Party):
Priscilla Brastianos, Massachusetts General Hospital
  Purpose

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


Condition Intervention Phase
Metastatic Malignant Neoplasm to Brain Drug: Palbociclib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Palbociclib in Progressive Brain Metastases Harboring Alterations in the CDK Pathway

Resource links provided by NLM:


Further study details as provided by Priscilla Brastianos, Massachusetts General Hospital:

Primary Outcome Measures:
  • 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%.


Secondary Outcome Measures:
  • Clinical Benefit Rate (Extracranial) [ Time Frame: 8 Weeks ]
    RECIST (CR, PR, SD)

  • 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 ]

Estimated Enrollment: 30
Study Start Date: November 2016
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Palbociclib
Other Name: Ibrance

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
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 http://medicine.iupui.edu/clinpharm/ddis/table.aspx; 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02896335


Contacts
Contact: Priscilla Brastianos, MD 617-724-8770 PBRASTIANOS@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Priscilla Brastianos, MD    617-724-8770    PBRASTIANOS@mgh.harvard.edu   
Principal Investigator: Priscilla Brastianos, MD         
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Eudocia K. Lee, MD    617-632-2166      
Principal Investigator: Eudocia Lee, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Pfizer
Investigators
Principal Investigator: Priscilla Brastianos, MD Massachusetts General Hospital
  More Information

Responsible Party: Priscilla Brastianos, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02896335     History of Changes
Other Study ID Numbers: 16-254
First Submitted: August 30, 2016
First Posted: September 12, 2016
Last Update Posted: August 29, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Priscilla Brastianos, Massachusetts General Hospital:
Recurrent Brain metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Brain Diseases
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases
Palbociclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action