Palbociclib and Pembrolizumab In Central Nervous System Metastases

NCT02896335 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 16-254
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying This research study is studying the efficacy and safety of the following study drugs as a possible treatment for recurrent central nervous system (CNS) metastases:

• Palbociclib alone (Cohort 1)
• The combination of palbociclib and pembrolizumab (Cohort 2) Pfizer and Merck, pharmaceutical companies, are supporting this research study by providing the study drugs as well as funding for research activities.

Conditions

Metastatic Malignant Neoplasm to Brain; Recurrent Brain Metastases; Progressive Brain Metastases

Keywords

Recurrent Brain metastases; Progressive Brain Metastases; Recurrent brain metastases from breast cancer; central nervous system metastases

Outcome Measures

Primary Outcomes (2)

• Intracranial Clinical Benefit Rate (Cohort 1)

  Intracranial Clinical Benefit is defined by complete response (CR), partial response (PR) or stable disease (SD) in the central nervous system (CNS). The proportion of patients in Cohort 1 with response in the CNS will be presented with a two-sided, 90% confidence interval based on the method of Atkinson and Brown, which allows for the two-stage design.

  8 weeks (Screening through 8 weeks)

• Intracranial Clinical Benefit Rate (Cohort 2)

  Intracranial clinical benefit is defined by CR, PR, or SD in the CNS. The proportion of Cohort 2 participants with response in the CNS will be presented with a two-sided, 90% exact binomial confidence interval.

  8 weeks (Screening through 8 weeks)

Secondary Outcomes (5)

• Extracranial Overall Response Rate

  8 weeks (Screening through 8 weeks)

• Intracranial disease progression rate of Cohort 1

  Time from registration to the earlier of progression or death due to any cause, up to 2 years post End of Treatment (EoT) visit.

• Extracranial disease progression rate of Cohort 1

  Time from registration to the earlier of progression or death due to any cause, for up to 2 years post EoT visit.

• Overall Survival (OS) Rate

  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.

• Incidence of Drug Related Toxicities

  Day 1 of study treatment through 30 days post last dose, an average of 1.5 years.

Study Arms (2)

Cohort 1 (Palbociclib)

EXPERIMENTAL

This arm involves screening for eligibility, study treatment and study visits, and follow up. Cohort 1 participants will receive palbociclib daily at a pre-determined dose for 21 days (Day 1-21) per 28-day cycle. Palbociclib is taken orally. Participants may receive study drug as long as they do not meet the criteria for ending treatment (no intolerable side effects and disease is not progressing). Participants will be followed for up to 2 years after their treatment with the study drug ends. Up to 30 participants will be enrolled in Cohort 1.

Drug: Palbociclib

Cohort 2 (Palbociclib in Combination with Pembrolizumab)

EXPERIMENTAL

Cohort 2 involves screening for eligibility, study treatment and study visits, and follow up. Participants in Cohort 2 will receive study drugs palbociclib and pembrolizumab. Palbociclib is taken orally once per day for 21 days (Day 1-21) of each 28-day cycle. Pembrolizumab will be administered as an intravenous (IV) infusion once every 21 days. Participants may receive study drugs as long as they do not meet the criteria for ending treatment (no intolerable side effects and disease is not progressing), and will be followed for up to 2 years after they stop study treatment. Up to 15 participants will be enrolled in Cohort 2.

Drug: Palbociclib; Drug: Pembrolizumab

Interventions

Palbociclib DRUG

Administered orally once per day on days 1-21 of 28-day cycles.

Also known as: Ibrance

Cohort 1 (Palbociclib); Cohort 2 (Palbociclib in Combination with Pembrolizumab)

Pembrolizumab DRUG

Pembrolizumab is administered via intravenous (IV) infusion at a dose of 200 mg over 30 minutes once every 21 days. Pembrolizumab cycles are 3 weeks (21 days) long in this study, and participants in Cohort 2 can receive pembrolizumab as long as they are receiving study drug palbociclib.

Also known as: MK-3475, Keytruda

Cohort 2 (Palbociclib in Combination with Pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed disease from any solid tumor (Cohort 1)
• Participants must have histologically or cytologically confirmed disease from breast cancer (Cohort 2).
• 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 of 0, 1 or 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

You may not qualify if:

• 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 ≥ grade 2 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 (Cohort 1). Leptomeningeal involvement is allowed for Cohort 2.
• 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.
• If a participant inadvertently becomes pregnant while on treatment with pembrolizumab, the participant will be immediately discontinued from study intervention(s). The site will contact the participant at least monthly and document the participant's status until the pregnancy has been completed or terminated. The outcome of the pregnancy will be reported to Merck within 2 working days if the outcome is a serious adverse experience (e.g. death, abortion, congenital anomaly, or other disabling or life-threatening complication to the mother or newborn). The study Investigator will make every effort to obtain permission to follow the outcome of the pregnancy and report the condition of the fetus or newborn to Merck. If a male participant impregnates his female partner, the study personnel at the site must be informed immediately and the pregnancy must be reported to the Overall PI, Merck and Pfizer and followed as necessary.
• 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 (Cohort 1). In Cohort 2, HIV-positive patients will NOT be permitted.
• 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).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Pfizer: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Interventions

palbociclib; pembrolizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Priscilla Brastianos, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Priscilla Brastianos, MD

CONTACT

617-724-8770; PBRASTIANOS@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 12, 2016
• Study Start: February 2, 2017
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)