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AzTrials

Breast CancerPhase 1/2NCT00765765

Ixabepilone and Hydroxychloroquine in Treating Patients With Metastatic Breast Cancer

A Phase 1/2 study testing hydroxychloroquine and ixabepilone in people with Breast Cancer, run by University of Medicine and Dentistry of New Jersey at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Breast Cancer
What is being tested?
hydroxychloroquine and ixabepilone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
2 sitesUnited States
Study dates
Feb 2009to Dec 2011
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Cancer Institute of New Jersey at Hamilton

    Hamilton, New Jersey, 08690

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

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Breast Cancer
Being tested
hydroxychloroquine, ixabepilone
Keywords
stage IV breast cancer, recurrent breast cancer, male breast cancer
Medical subject headings
Breast Neoplasms, Breast Neoplasms, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • hydroxychloroquineDrug

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

  • ixabepiloneDrug

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

Study groups in NCT00765765
Study groupRoleWhat they receive
Ixabepilone and hydroxychloroquineExperimentalNot described
Receives: Drug: hydroxychloroquine; Drug: ixabepilone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 3 years

Secondary outcomes (6)
  1. Duration of Response

    Measured: 5 years

  2. Time to Progressive Disease

    Measured: 5 years

  3. Survival Time

    Measured: 5 years

  4. Pharmacodynamic Markers for Autophagy Detection

    Measured: 2 years

  5. Effects of Hydroxychloroquine on Autophagy

    Measured: 2 years

  6. Correlation of Estrogen Receptor, Progesterone Receptor and/or HER2 Status With Treatment Response

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2008 (estimated)
  2. Study startFeb 2009
  3. Primary completionDec 2011
  4. Study completionDec 2011

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00765765
Sponsor's protocol ID
CDR0000615000
Other IDs
P30CA072720, CINJ-040804, 0220080205
Status last verified
Jul 2023
First submitted
2 Oct 2008
Last updated
9 Aug 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing hydroxychloroquine and ixabepilone in people with Breast Cancer, run by University of Medicine and Dentistry of New Jersey at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor Response Rate (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2023.

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