Ixabepilone and Hydroxychloroquine in Treating Patients With Metastatic Breast Cancer

NCT00765765 | Terminated Phase 1 Results

• 4 other identifiers: CDR0000615000P30CA072720CINJ-0408040220080205
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hydroxychloroquine may help ixabepilone work better by making tumor cells more sensitive to the drug. PURPOSE: This phase I/II trial is studying the side effects and best dose of ixabepilone given together with hydroxychloroquine and to see how well they work in treating patients with metastatic breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (1)

• Tumor Response Rate

  Overall Complete Response and Partial Response will be considered tumor response. Ixabepilone as a single agent (40 mg/m2 as an intravenous infusion every 3 weeks) was evaluated in a previous (Phase II) study in women with metastatic breast cancer and that the objective tumor response rate was 11.5%. In another(Phase III) study, Ixabepilone in combination with capecitabine resulted in an objective tumor response rate of 35%, compared to that of capecitabine alone (14%). Therefore, in the Phase II portion of the ixabepilone plus hydroxychloroquine combination treatment study, a tumor response rate of less than 15% will be deemed uninteresting. The target tumor response rate will be 35%. Due to uncertainty about the true response rate of ixabepilone plus hydroxychloroquine combination on this patient poupation, we also will consider a response rate of 30% to be encouraging.

  3 years

Secondary Outcomes (6)

• Duration of Response

  5 years

• Time to Progressive Disease

  5 years

• Survival Time

  5 years

• Pharmacodynamic Markers for Autophagy Detection

  2 years

• Effects of Hydroxychloroquine on Autophagy

  2 years

Study Arms (1)

Ixabepilone and hydroxychloroquine

EXPERIMENTAL

Drug: hydroxychloroquine; Drug: ixabepilone

Interventions

hydroxychloroquine DRUG

Dose escalation from 200 mg po qd to 200 mg po bid.

Ixabepilone and hydroxychloroquine

ixabepilone DRUG

Starting dose of 40 mg/m2 and can dose reduce to 32 mg/m2.

Ixabepilone and hydroxychloroquine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed breast cancer * Histologic or cytologic elements can be established on metastatic tumor aspirate or biopsy * Metastatic disease * Measurable disease according to RECIST criteria * Must have received 2 prior chemotherapy regimens for metastatic breast cancer * Anthracycline-resistant (or treated with minimum cumulative doxorubicin dose of 240 mg/m\^2 or epirubicin dose of 360 mg/m\^2) and taxane-resistant disease * Anthracycline resistance is defined as progression while on therapy or within 6 months in the adjuvant/neoadjuvant setting or 3 months in the metastatic setting * Taxane resistance is defined as progression while on therapy or within 12 months in the adjuvant/neoadjuvant setting or 4 months in the metastatic setting * Hormone receptor status known * No known CNS metastases or previously treated and now stable CNS metastases PATIENT CHARACTERISTICS: * Menopausal status not specified * ECOG performance status 0-2 * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL * Total bilirubin ≤ upper limit of normal (ULN) * If patient has Gilbert's disease, then patient must have isolated hyperbilirubinemia (e.g., no other liver function test abnormality), with maximum bilirubin ≤ 2 times ULN * AST and ALT ≤ 2.5 times ULN, independently of liver metastases * Alkaline phosphatase ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN OR calculated creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other active malignancy * History of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix within the past 3 years allowed provided patient has been treated with curative intent * History of prior malignancy allowed provided patient has been treated with curative intent and has been disease free \> 3 years * None of the following conditions within the past 6 months: * Myocardial infarction * Stroke * Symptomatic peripheral vascular disease * No unstable angina or NYHA class II-IV congestive heart failure * No history of psoriasis or porphyria * No history of hypersensitivity to 4-aminoquinoline compound * No retinal or visual field changes from prior 4-aminoquinoline-compound use * No history of G6PD deficiency * No GI pathology that would interfere with drug bioavailability * No motor or sensory neuropathy ≥ grade 2 (NCI CTCAE) at study entry * No serious uncontrolled medical disorder or active infection at study entry * No rheumatoid arthritis or systemic lupus erythematosus requiring active treatment * No history of HIV * No history of any condition (social or medical) that, in the opinion of the investigator, might interfere with the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior radiation to tumor sites allowed provided: * Radiation was completed ≥ 3 weeks prior to study treatment * All radiation-related toxicities have resolved to ≤ grade 1 * No more than 3 prior chemotherapy regimens in the metastatic setting * No prior ixabepilone or another epothilone * No concurrent highly active antiretroviral therapy * No other concurrent hydroxychloroquine for treatment or prophylaxis of malaria * No other concurrent anticancer investigational or commercial agents or therapies

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Medicine and Dentistry of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Cancer Institute of New Jersey at Hamilton

Hamilton, New Jersey, 08690, United States

Location

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Hydroxychloroquine; ixabepilone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Vassiliki Karantza
• Organization: Cancer Institute of New Jersey

karantva@cinj.rutgers.edu; rizzoji@cinj.rutgers.edu; zelinsta@cinj.rutgers.edu

732-235-8675

Study Officials

• Vassil Karantza-Wadsworth, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: October 2, 2008
• First Posted: October 3, 2008
• Study Start: February 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: August 9, 2023
• Results First Posted: December 25, 2013

Record last verified: 2023-07

Locations

US (2)