Ixabepilone and Hydroxychloroquine in Treating Patients With Metastatic Breast Cancer

University of Medicine and Dentistry of New Jersey

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Breast Cancer

Treatments

Drug: ixabepilone

Drug: hydroxychloroquine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00765765

P30CA072720 (U.S. NIH Grant/Contract)

CDR0000615000

CINJ-040804 (Other Identifier)

0220080205 (Other Identifier)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

The primary objective of this study is to assess the antitumor activity, measured by tumor response rate, in patients who receive this regimen as a third-line treatment. (Phase II)

Secondary

To measure the duration of response for responding patients.
To measure the time to progressive disease.
To measure survival time.
To characterize the quantitative and qualitative toxicities of this regimen in these patients.
To develop pharmacodynamic markers for autophagy detection in patient specimens.
To characterize the effects of hydroxychloroquine on autophagy in patients in vivo.
To investigate whether the estrogen receptor, progesterone receptor, and/or HER2 status of breast tumors correlates with treatment response.

OUTLINE: This is a multicenter, phase I dose-escalation study of ixabepilone followed by a phase II study.

During the first course, patients receive ixabepilone IV over 3 hours on day 1 and oral hydroxychloroquine twice daily on days 3-21. On all subsequent courses, patients receive ixabepilone IV over 3 hours on day 1 and oral hydroxychloroquine twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 6 months.

Enrollment

6 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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