Exemestane and Cyclophosphamide for Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT01963481
• Recruitment Status: Completed
• First Posted: October 16, 2013
• Results First Posted: March 17, 2020
• Last Update Posted: March 17, 2020
• Sponsor: NYU Langone Health
• Information provided by (Responsible Party): NYU Langone Health

Study Description

Brief Summary:

This phase II trial studies how well exemestane and cyclophosphamide work in treating patients with estrogen receptor (ER) -positive, progesterone receptor (PR) -positive, and human epidermal growth factor receptor (HER)2-negative stage IV breast cancer.

Condition or disease	Intervention/treatment	Phase
Metastatic Beast Cancer	Drug: Exemestane; Drug: Cyclophosphamide	Phase 2

Detailed Description:

Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells. Low dose cyclophosphamide may also stimulate the white blood cells, including natural killer cells, for instance by decreasing the suppressor (regulatory) T-cells. Giving exemestane with cyclophosphamide may be an effective treatment for estrogen receptor-positive, progesterone receptor-positive, and HER2-negative stage IV breast cancer.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Exemestane With Immunomodulatory Cyclophosphamide in ER and/or PR-positive and HER2/Neu Negative Metastatic Breast Cancer
• Study Start Date: September 2013
• Actual Primary Completion Date: October 1, 2017
• Actual Study Completion Date: October 1, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Exemestane and cyclophosphamide; A treatment cycle is defined as 4 weeks: One tablet (25 mg) of exemestane and one tablet (50 mg) of cyclophosphamide given daily by mouth until disease progression or unacceptable adverse events.	Drug: Exemestane; Other Name: Aromasin; Drug: Cyclophosphamide; Other Names: Cytoxan; CTX

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) Rate at 3 Months [ Time Frame: 3 months ]
   PFS is defined as the time from first treatment day until objective disease progression or death from any cause. Assessment of disease progression based on Response Evaluation Criteria in Solid Tumor (RESIST) guideline version 1.1 is performed every 12 weeks on study. The percent of participants with PFS at 3 months will be reported.

Secondary Outcome Measures :

1. Response Rate (RR) - Complete Response and Partial Response [ Time Frame: 2 years ]
   Complete response (CR) is defined as the disappearance of all target lesions, while partial response (PR) is when at least a 30% decrease in the sum of the diameters of target lesions. Evaluation of response is based on RESIST guideline version 1.1. RR is reported as percentage of participants with a CR and/or PR at 2 years.
2. Clinical Benefit Rate Score [ Time Frame: 3 years ]
   Clinical benefit rate is defined as the percentage of patients who have achieved objective response or stable disease for at least 24 weeks. Evaluation of response and disease progression is based on RESIST guideline version 1.1. Response and progression are assessed every 12 weeks.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients must have histologically confirmed breast cancer that is ER positive and/or PR positive, and HER2/neu negative and have disease that is metastatic (stage IV)

  • HER2/neu negative disease determined using commercially available/approved assay in local institutional or reference laboratory, according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (IHC 0-1+ or 2+ with HER2/17 ratio on FISH <= 1.8).
  • ER/PR expression performed by standard immunohistochemical assay and classified as ER and/or PR-positive according to ASCO/CAP guidelines (1-100% expression)
  • Histologic and/or cytologic confirmation of metastatic disease is encouraged whenever feasible, furthermore, if feasible, the biopsy should confirm that the metastatic tumor is ER and/or PR positive and HER2/neu negative. For patients in whom histologic biopsy confirmation and/or assessment of ER/PR/HER2 of metastatic disease is not feasible, it is required that the primary tumor be ER and/or PR-positive and HER2/neu negative.
• Measurable disease (RECIST 1.1) or non-measurable (assessable) disease
• Patients must have had progressive disease during at least one line of endocrine therapy for metastatic disease or have recurrent disease while or within 12 months of receiving adjuvant endocrine therapy. Prior treatments accepted include a non-steroidal aromatase inhibitor, tamoxifen, fulvestrant or combinations.
• Patients taking bisphosphonates for bone disease are permitted to enter the trial, but their bone lesions are not considered to be assessable for response, although they are assessable for progression.
• Female or male subjects age >= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count >= 1,200/mcL
• platelets >= 100,000/mcL
• hemoglobin >= 9g/dl
• total bilirubin <= 2 X upper limit of normal (ULN) [unless due to Gilbert's disease]
• AST(SGOT) <= 2.5 X ULN
• ALT(SGPT) <= 2.5 X ULN
• creatinine <= 1.5 X ULN
• Patients must be able to swallow and tolerate oral medications.
• Postmenopausal status, defined as 60 years and older, being 45 years and older and having amenorrhea x 12 months or follicle stimulating hormone levels within postmenopausal range, OR having undergone a bilateral oophorectomy.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients may not be receiving any other investigational agents.
• Prior treatment for breast cancer with a steroidal aromatase inhibitor; with the exception of patients who were started on the combination of exemestane with everolimus less than 4 weeks prior to study entry and discontinued everolimus due to poor tolerability.
• Presence of life threatening metastatic visceral disease (defined as extensive hepatic involvement or symptomatic pulmonary lymphangitic spread) or uncontrolled brain metastases.
• 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.

Contacts and Locations

Locations

United States, New York

NYU Cancer Center

New York, New York, United States, 10016

Sponsors and Collaborators

NYU Langone Health

Investigators

• Principal Investigator: Sylvia Adams, MD; NYU Perlmutter Cancer Center

  Study Documents (Full-Text)

Documents provided by NYU Langone Health:

Study Protocol and Statistical Analysis Plan  [PDF] September 12, 2013

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kwa M, Li X, Novik Y, Oratz R, Jhaveri K, Wu J, Gu P, Meyers M, Muggia F, Speyer J, Iwano A, Bonakdar M, Kozhaya L, Tavukcuoglu E, Budan B, Raad R, Goldberg JD, Unutmaz D, Adams S. Serial immunological parameters in a phase II trial of exemestane and low-dose oral cyclophosphamide in advanced hormone receptor-positive breast cancer. Breast Cancer Res Treat. 2018 Feb;168(1):57-67. doi: 10.1007/s10549-017-4570-4. Epub 2017 Nov 9.

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT01963481
• Other Study ID Numbers: 13-00761
• First Posted: October 16, 2013
• Results First Posted: March 17, 2020
• Last Update Posted: March 17, 2020
• Last Verified: March 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by NYU Langone Health:

hormonal therapy; immunotherapy

Additional relevant MeSH terms:

Cyclophosphamide; Exemestane; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists