Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies

NCT01554371 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 11996NCI-2012-00436
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of eribulin (Halaven™) and cyclophosphamide (Cytoxan®) given together at different doses. This study will look at what effects, good and/or bad, that these drugs have on solid tumors. Eribulin is a drug that has been approved by the FDA for breast cancer that has spread to other parts of the body. Cyclophosphamide has been approved for different types of cancers (including breast cancer). However, the combination of eribulin and cyclophosphamide is considered experimental; that means this combination has not been approved by the FDA. The funding for this study is provided by Eisai Inc., the maker of eribulin.

Conditions

Malignant Solid Tumour; Breast Cancer Nos Metastatic Recurrent; Neuropathy

Keywords

Solid tumor; Metastatic breast cancer; Unresectable or metastatic carcinoma; Neuropathy; Eribulin; Cyclophosphamide

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) in Participants With Any Solid Tumor (Phase Ib)

  Standard dose-confirmation design of 3 to 6 participants per cohort (3+3 design) was used to determine the MTD of eribulin in combination with cyclophosphamide for participants with any solid tumor. The highest dose level or MTD is reached when no more than one of six participants experience a Dose Limiting Toxicity (DLTs). A DLT is defined as any treatment-related toxicity in first 28 days of therapy with a grade 3 or 4 non-hematologic toxicity, a grade 4 neutropenia or thrombocytopenia lasting \>7 days or febrile neutropenia, or any clinically significant toxicity grade 2 or higher that requires more than 14 days to resolve. The highest dose level at which no more than one of six participants experience DLT defines the MTD.

  Up to 24 months

• Clinical Benefit Rate for Patients With Advanced Breast Cancer (ABC) (Phase II)

  The clinical benefit rate is defined as the proportion of participants with confirmed complete response (CR), partial response (PR) and stable disease (SD) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Responses are determined by changes in the largest diameter of the tumor lesions and the shortest diameter in the case of malignant lymph nodes. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter, PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Only participants with measurable disease present at baseline, received at least 1 cycle of therapy, and had disease re-evaluated will be considered evaluable.

  Up to 24 months

Secondary Outcomes (4)

• Number of Participants With Treatment-related Toxicities

  Up to 24 months

• Number of Participants With Dose Limiting Toxicity (DLT) for Participants With Any Solid Tumor (Phase 1b)

  Up to 24 months

• Overall Response Rate (ORR) for Participants With Advanced Breast Cancer (Phase II)

  Up to 24 months

• Time to Progression for Participants With Advanced Breast Cancer (Phase II)

  Up to 24 months

Study Arms (3)

Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)

EXPERIMENTAL

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.1 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Drug: Eribulin; Drug: Cyclophosphamide

Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort)

EXPERIMENTAL

Dose escalation cohort will include all patients with solid tumors. Eribulin mesylate 1.4 mg/ m2 on days 1 and 8 followed by cyclophosphamide 600 mg/ m2 on day 1 of a 21-day cycle.The highest dose level at which no more than one of six subjects experience DLT defines the MTD

Drug: Eribulin; Drug: Cyclophosphamide

Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)

EXPERIMENTAL

Dose-expansion cohort will enroll patients with advanced breast cancer only after Phase Ib enrollment has been concluded. The MTD of Eribulin mesylate will be administered on days 1 and 8 followed by cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle.

Drug: Eribulin; Drug: Cyclophosphamide

Interventions

Eribulin DRUG

Given intravenously (IV) Phase II: Eribulin mesylate (mg/m2) + Cyclophosphamide (mg/ m2) for advanced breast cancer participants only

Also known as: Halaven, E7389, ER-086526

Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort); Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort); Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)

Cyclophosphamide DRUG

Given IV

Also known as: Cytoxan

Phase 1b: 1.1 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort); Phase 1b: 1.4 mg/m2 Eribulin Combination w/ Cyclophosphamide (Solid Tumor Escalation Cohort); Phase II: Eribulin Combination w/ Cyclophosphamide (Breast Cancer Expansion Cohort)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase Ib: Patient must have histologically or cytologically documented solid tumor malignancies.
• Phase II: Patients must have histologically or cytologically confirmed locally advanced, unresectable or metastatic carcinoma of the breast.
• Patient is male or female and ≥18 years of age on the day of signing informed consent.
• Patient must have performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale and life expectancy \> 3 months.
• Patient must have evaluable disease. Measureable disease is not required
• Patient must have adequate organ function
• Female patient of childbearing potential must have a negative serum or urine pregnancy test quantitative human chorionic gonadotropin (β-hCG) within 72 hours prior to receiving the first dose of study medication and agree to the use of effective methods of contraception while on study.
• Any number of prior lines of chemotherapy in the metastatic setting is allowed.
• Concomitant use of bisphosphonates is allowed.
• Patients with stable and clinically insignificant CNS disease are allowed. Patients must be off steroids with no new CNS symptoms or findings on radiographic imaging for 1 month.
• Patients willing and able to complete the questionnaires.
• Patients willing and able to comply with the study protocol for the duration of the study.
• Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within two weeks, 4 weeks for nitrosoureas, mitomycin C, pegylated-doxorubicin and one half-life for bevacizumab, hormone therapy within one week, trastuzumab within 2 weeks or lapatinib within one week of study Day 1.
• If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1.
• Patients with non-healing surgical wounds. Patients must be at least two weeks from a major surgical procedure, and surgical wounds must be completely healed.
• Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:
• no evidence of new or enlarging CNS metastasis
• off steroids that are used to minimize surrounding brain edema. Patients with clinically insignificant brain metastases that do not require treatment are eligible.
• Patients with known hypersensitivity to the components of study drug or its analogs.
• Significant cardiovascular impairment:
• Congestive heart failure, Clinically significant cardiac arrhythmia, history or current evidence of a myocardial infarction during the last 6 months, and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator, or unstable angina
• QTc prolongation \>480 msec (Bazett's Formula) or congenitally long QT syndrome (LQTS)
• Severe/uncontrolled concurrent illness/infection
• Patients with other active, current primary malignancies, other than carcinoma in situ of the cervix or non-melanoma skin cancer
• Patients with \> Grade 1 neuropathy at screening
• Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative
• Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Eisai Inc.: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Gumusay O, Huppert LA, Magbanua MJM, Wabl CA, Assefa M, Chien AJ, Melisko ME, Majure MC, Moasser M, Park J, Rugo HS. A phase Ib/II study of eribulin in combination with cyclophosphamide in patients with advanced breast cancer. Breast Cancer Res Treat. 2024 Jan;203(2):197-204. doi: 10.1007/s10549-023-07073-0. Epub 2023 Oct 10.

  PMID: 37815684 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma

Interventions

eribulin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Hope Rugo, MD
• Organization: University of California, San Francisco

Hope.Rugo@ucsf.edu

(415) 353-7618

Study Officials

• Hope S Rugo, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 9, 2012
• First Posted: March 15, 2012
• Study Start: March 27, 2012
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: February 3, 2021
• Results First Posted: February 3, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)