Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer

NCT02768701 | Completed Phase 2 Results DMC

• 1 other identifier: LCCC 1525
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate pembrolizumab therapy in patients with triple-negative breast cancer (TNBC) who have received at least one prior line of therapy.

Conditions

Triple Negative Breast Cancer

Keywords

Pembrolizumab; cyclophosphamide

Outcome Measures

Primary Outcomes (2)

• The Progression Free Survival (PFS)

  PFS is defined as the time from day1 of the study treatment until disease progression or death. Disease progression is defined as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST)1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images or assessment of the physician. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Up to 5 years

• Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment.

  Regulatory T cells (Tregs) are counted before the treatment start and during the treatment. Methods: Blood Sample collection.

  Up to 2 years

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 3 years

• Disease Control Rate (DCR)

  Up to 2 years

• Overall Survival (OS)

  Up to 3 years

• Treatment Associated Toxicity

  Up to 3 years

Study Arms (1)

Experimental: Single Arm

EXPERIMENTAL

Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks.

Drug: Pembrolizumab; Drug: Cyclophosphamide

Interventions

Pembrolizumab DRUG

Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion.

Also known as: Keytruda

Experimental: Single Arm

Cyclophosphamide DRUG

A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.

Also known as: Cytoxan, Neosar

Experimental: Single Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Have measurable disease based on RECIST 1.1 (see section 6.7 for details).
• ECOG Performance Status ≤ 1 as defined in the protocol ECOG Performance Status.
• Subject must have histologically confirmed stage IV TNBC (ER-, PR-, HER2-negative) and have received at least 1 prior line of systemic therapy.
• ER- and PR-negative: defined as \< 1% staining by immunohistochemistry (IHC)
• HER2-negative disease, defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio \< 2.0
• Patients with stable brain metastases will be allowed provided the following criteria are met:
• Brain radiation was already provided at least 4 weeks prior to initiating study treatment
• The subject has no new or progressive neurologic symptoms AND neurological symptom stability for the last 4 weeks prior to the study
• The subject has been off of corticosteroids for at least 7 days prior to trial treatment
• The subject does not have carcinomatous meningitis
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 h of initiating study treatment.
• Females of childbearing potential must have a negative serum pregnancy test within 72 hrs prior to treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile, have a congenital acquired condition that prevents childbearing (have undergone a hysterectomy, bilateral tubal ligation/occlusion, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to screening) or they are naturally postmenopausal for at least 12 consecutive months without an alternative medical cause. In women \< 45 years of age a high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Female patients of childbearing potential should be willing to use appropriate birth control as outlined in Section 5.2.8, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.

You may not qualify if:

• Active infection requiring systemic therapy
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to receipt of study medication or who has not recovered (i.e., ≤ Grade 1 or at baseline; excludes alopecia and Grade 2 neuropathy) from adverse events due to a previously administered agent.
• If subject had major surgery, they must have recovered adequately from the toxicity and complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has had monoclonal antibody therapy within 4 weeks prior to study Day 1 or who has not recovered (ie, ≤ Grade 1 at baseline; excludes alopecia and Grade 2 neuropathy) from adverse events due to agent(s) administered more than 4 weeks earlier.
• Treatment with any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study medication.
• Used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis requiring treatment with steroids; has history of, or any evidence of, active interstitial lung disease.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

George Washington University-Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Cone Health Cancer Center

Greensboro, North Carolina, 27403, United States

Location

Rex Cancer Center

Raleigh, North Carolina, 27607, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Melahat G. Canter MD MS ACRP-CP, Clinical Trial Analyst
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

Melahat_Canter@med.unc.edu

(919) 962-0000

Study Officials

• Elizabeth C Dees, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: 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 5, 2016
• First Posted: May 11, 2016
• Study Start: October 18, 2016
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2023
• Last Updated: May 22, 2023
• Results First Posted: August 3, 2022

Record last verified: 2023-05

Locations

US (5)