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Phase I/II Study of Ixabepilone in Combination With the Autophagy Inhibitor Hydroxychloroquine for the Treatment of Patients With Metastatic Breast Cancer


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer

Thank you

Trial Information

Phase I/II Study of Ixabepilone in Combination With the Autophagy Inhibitor Hydroxychloroquine for the Treatment of Patients With Metastatic Breast Cancer


OBJECTIVES:

Primary

- To determine the recommended phase II dose of ixabepilone and hydroxychloroquine in
patients with metastatic breast cancer. (Phase I)

- 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended phase II dose of ixabepilone and hydroxychloroquine

Outcome Time Frame:

Phase I portion of study

Safety Issue:

Yes

Principal Investigator

Vassil Karantza-Wadsworth, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000615000

NCT ID:

NCT00765765

Start Date:

February 2009

Completion Date:

March 2011

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • male breast cancer
  • Breast Neoplasms

Name

Location

Cancer Institute of New Jersey at HamiltonHamilton, New Jersey  08690
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903