Palbociclib in Treating Patients With Metastatic HER-2 Positive Breast Cancer With Brain Metastasis

NCT02774681 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 15B08STU00202582P30CA060553NCI-2016-00626
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate if the study drug palbociclib has anti-tumor activity against the breast cancer that has spread to the brain and also to determine the overall radiographic response rate in the CNS. Palbociclib is an anti-cancer medication that has been shown to stop cancer cells from growing. It has been approved in hormone positive breast cancer, along with other hormone therapies and has been found to be effective. The preclinical studies suggest that the drug may also have activity in other types of breast cancer, such as HER2 positive breast cancer. The purpose of this study is to see if the study drug is effective in patients with brain metastasis, who have HER2-positive breast cancer.

Conditions

Breast Carcinoma Metastatic in the Brain; Estrogen Receptor Negative; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Radiographic Response Rate (RRR) in the CNS in Patients With HER2-positive Breast Cancer Who Have Brain Metastasis Treated With Palbociclib

  Assess the Radiographic Response Rate (RRR) in the CNS by modified Response Assessment in Neuro-Oncology Criteria Brain Metastasis (modifiedRANO-BM). Maximum response prior to disease progression will be used. In General: Complete Response : Disappearance of all lesions Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)

  Up to 3 years

Secondary Outcomes (5)

• Incidence of Adverse Events

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Progression Free Survival (PFS)

  Up to 3 years

• Overall Response Rate (ORR)

  Up to 3 years

• Time to CNS Progression

  Up to 3 years

Other Outcomes (4)

• Change in Cognitive Function in Patients Receiving Palbociclib

  At baseline, 2 months and 4 months

• Change in Genomic Landscape of Available CNS and Non-CNS Tumors

  At baseline

• Change in Quality of Life in Patients Receiving Palbociclib

  At baseline, 2 months and 4 months

Study Arms (1)

Treatment (palbociclib)

EXPERIMENTAL

Patients receive palbociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with HER2 positive breast cancer may also receive trastuzumab IV over 30-90 minutes every 3 weeks.

Procedure: Cognitive Assessment; Drug: Palbociclib; Procedure: Quality-of-Life Assessment; Biological: Trastuzumab

Interventions

Cognitive Assessment PROCEDURE

Ancillary studies

Treatment (palbociclib)

Palbociclib DRUG

Given PO

Also known as: Ibrance, PD-0332991, PD-332991

Treatment (palbociclib)

Quality-of-Life Assessment PROCEDURE

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (palbociclib)

Trastuzumab BIOLOGICAL

Given IV

Also known as: ABP 980, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, PF-05280014, rhuMAb HER2, RO0452317, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar PF-05280014

Treatment (palbociclib)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed HER2-positive metastatic breast cancer (estrogen and progesterone receptor 0%, HER-2 3+ by immunohistochemistry (IHC); if IHC score of 2, fluorescence in situ hybridization (FISH) ratio must be greater than 2.0; if FISH less than 2.0, HER2 copy number must be greater than 6; NOTE: Brain lesions are not required to have pathologic confirmation
• Patients should not have received \> 2 lines of chemotherapy for metastatic disease
• Patients must have a life expectancy of at least 12 weeks at the time of registration
• Eastern Cooperative Oncology Group (ECOG) performance status \>= 2
• Measurable disease in the brain, defined as at least 1 lesion measuring \>= 5 mm on imaging at the time of registration
• If patients are on corticosteroids, they must have been on a stable or decreasing dose \>= 5 days prior to obtaining their baseline gadolinium (Gd)-magnetic resonance imaging (MRI) of brain; this MRI is to be obtained within 28 days of registration; NOTE: If patient needs escalation of steroids prior to therapy, or are on unstable doses of steroids they are not eligible
• Patients who underwent neurosurgery (NSGY) or stereotactic radiosurgery (SRS) to a brain lesion must have a new measureable lesion; NOTE: SRS may be done to a lesion that will not be used for response evaluation and should be done \> 2 weeks prior to registration; any NSGY procedure must have been completed \> 3 weeks prior to registration
• Patients must not have received systemic therapy within 2 weeks of initiating palbociclib; NOTE: For the HER2-positive cohort, patients on trastuzumab can remain on the drug; no break or washout period required; however, lapatinib, ado-trastuzumab-emtansine, and pertuzumab are prohibited and a minimum wash out period of 2 weeks is required
• Patients must exhibit adequate bone marrow, liver, and renal function, within 14 days prior to registration, defined as:
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (growth factor support is permitted)
• Platelets \>= 100,000/mm\^3 (may be reached by transfusion)
• Hemoglobin \>= 10 gm/dl (may be reached by transfusion)
• Glutamate pyruvate transaminase (GPT)/glutamate oxaloacetate transaminase (GOT) \< 3 x upper limit of normal (ULN) (or \< 5 x ULN in case of liver metastasis)
• Bilirubin \< 3 x ULN (or \< 5 x ULN in case of liver metastasis)
• Creatinine \< 1.5 x ULN

You may not qualify if:

• Any uncontrolled neurological symptom attributed to CNS metastasis
• Brain metastasis must not be impending herniation or other significant vasogenic edema requiring increasing steroid doses; lesions must not have frank hemorrhage
• Patients with leptomeningeal disease are not eligible for participation
• Any significant medical illnesses or infection that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are not eligible for participation
• Known human immunodeficiency virus (HIV) positive status
• Known active hepatitis B and/or C
• Previous treatment with palbociclib
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib are not eligible; AND/OR patients who have had prior exposure to compounds of similar chemical or biologic composition to palbociclib are not eligible hypersensitivity to any component of palbociclib are not eligible for participation
• Patients being treated with any other experimental agents/clinical trials are not eligible for participation; if the patient is on any investigational agent, a wash-out period of minimum 2 weeks prior to registration is mandatory for the patient to be eligible for the study
• Patients who are on any prohibited medication; a wash-out period of minimum 2 weeks prior to registration is mandatory for the patient to be eligible for the study
• Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure
• Unstable angina pectoris

Sponsors & Collaborators

• Northwestern University: lead
• Pfizer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

Houston Methodist Hospital/Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Mental Status and Dementia Tests; palbociclib; Trastuzumab; PF-05280014

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was closed before the accrual goal was met due to slow accrual.

Results Point of Contact

• Title: Massimo Cristofanilli, MD
• Organization: Northwestern University

Massimo.cristofanilli@nm.org

312-503-5488

Study Officials

• Cristofanilli Massimo, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 17, 2016
• Study Start: August 31, 2016
• Primary Completion: February 13, 2019
• Study Completion: February 16, 2020
• Last Updated: April 14, 2020
• Results First Posted: February 24, 2020

Record last verified: 2020-04

Locations

US (3)