Ixabepilone and Hydroxychloroquine in Treating Patients With Metastatic Breast Cancer

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry of New Jersey )
ClinicalTrials.gov Identifier:
NCT00765765
First received: October 2, 2008
Last updated: November 6, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: hydroxychloroquine
Drug: ixabepilone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Ixabepilone in Combination With the Autophagy Inhibitor Hydroxychloroquine for the Treatment of Patients With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Tumor Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Time to Progressive Disease [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Survival Time [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Pharmacodynamic Markers for Autophagy Detection [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Effects of Hydroxychloroquine on Autophagy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Correlation of Estrogen Receptor, Progesterone Receptor and/or HER2 Status With Treatment Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: February 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ixabepilone and hydroxychloroquine Drug: hydroxychloroquine
Dose escalation from 200 mg po qd to 200 mg po bid.
Drug: ixabepilone
Starting dose of 40 mg/m2 and can dose reduce to 32 mg/m2.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00765765

Locations
United States, New Jersey
Cancer Institute of New Jersey at Hamilton
Hamilton, New Jersey, United States, 08690
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
University of Medicine and Dentistry of New Jersey
Investigators
Principal Investigator: Vassil Karantza-Wadsworth, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Rutgers, The State University of New Jersey ( University of Medicine and Dentistry of New Jersey )
ClinicalTrials.gov Identifier: NCT00765765     History of Changes
Other Study ID Numbers: CDR0000615000, P30CA072720, CINJ-040804, 0220080205
Study First Received: October 2, 2008
Results First Received: November 6, 2013
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
stage IV breast cancer
recurrent breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hydroxychloroquine
Epothilones
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 31, 2014