Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

NCT03012230 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MC1534NCI-2016-0205715-006282
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with pembrolizumab in treating patients with stage IV triple negative breast cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ruxolitinib phosphate together may work better in treating patients with stage IV triple negative breast cancer.

Conditions

Metastatic Malignant Neoplasm in the Bone; Stage IV Breast Cancer AJCC v6 and v7; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients. Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  Up to 21 days

• Incidence of adverse events

  Assessed by NCI CTCAE version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by cohort and overall). Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The rate of grade 3 or higher non-hematologic adverse events, and the rate of grade 4 or higher adverse event (hematologic and non-hematologic) will be computed each with a 95% exact binomial confidence.

  Up to 28 days after last dose of study drug

Secondary Outcomes (1)

• Best response

  Up to 2 years

Other Outcomes (1)

• Assessment of PDJ amplification, PD-L1, PD-L2, JAK2 expression and pSTAT3

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, ruxolitinib phosphate)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 and ruxolitinib phosphate PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Drug: Ruxolitinib Phosphate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, ruxolitinib phosphate)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, ruxolitinib phosphate)

Ruxolitinib Phosphate DRUG

Given PO

Also known as: INCB-18424 Phosphate, Jakafi

Treatment (pembrolizumab, ruxolitinib phosphate)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Metastatic (stage IV) triple negative breast cancer that has progressed after at least one prior chemotherapy regimen in the metastatic setting or refusal of chemotherapy in the metastatic setting; non-measurable disease (i.e. bone metastases) is permitted
• Histological confirmation of triple negative breast cancer defined as:
• Her2/neu by fluorescence in situ hybridization (FISH) (ratio =\< 1.8) or immunohistochemistry (IHC) (0 or 1+)
• Estrogen receptor (ER) and progesterone receptor (PR) expression \< 10%
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 7 days prior to registration)
• Platelet count \>= 100,000/mm\^3 (obtained =\< 7 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit normal (ULN) (obtained =\< 7 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN or \< 5 x ULN if organ involvement (obtained =\< 7 days prior to registration)
• Alkaline phosphatase \< 5 x ULN (obtained =\< 7 days prior to registration)
• Serum creatinine =\< 2 x ULN or 24 hour creatinine (Cr) clearance \> 60 ml/min (obtained =\< 7 days prior to registration)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Ability to provide informed written consent and be able to adhere to the study visit schedule and other protocol requirements
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willing to provide blood samples for correlative research purposes

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, known positive for active infectious hepatitis, type A, B or C (past infection allowed), or psychiatric illness/social situations that would limit compliance with study requirements; Note: ongoing infection controlled on antibiotics/antifungal/antiviral medications are allowed
• Any of the following prior therapies:
• Cytotoxic chemotherapy =\< 14 days prior to registration
• Immunotherapy =\< 14 days prior to registration
• Biologic therapy (i.e. antibody therapies) =\< 28 days prior to registration
• Radiation therapy =\< 14 days prior to registration
• Targeted therapies (i.e. PARP inhibitors, =\< 7 days or 5 half-lives whichever is shorter)
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =\< 14 days prior to registration
• Active uncontrolled central nervous system (CNS) metastases
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
• Hypersensitivity to ruxolitinib or any of its excipients
• Major surgery =\< 28 days prior to registration; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Clinically significant heart disease, including the following:
• Active severe angina pectoris prior to registration
• Acute myocardial infarction prior to registration

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab; ruxolitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Donald W Northfelt

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 6, 2017
• Study Start: December 6, 2017
• Primary Completion: January 6, 2023
• Study Completion: March 8, 2023
• Last Updated: January 31, 2024

Record last verified: 2024-01

Locations

US (1)