Study of a Novel Indibulin Dosing Schedule for the Treatment of Metastatic Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Ziopharm.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):
Ziopharm
ClinicalTrials.gov Identifier:
NCT01113970
First received: April 8, 2010
Last updated: January 29, 2013
Last verified: July 2012
  Purpose

This study is a Phase I/II trial of a novel Indibulin dosing schedule for the treatment of metastatic breast cancer. Eligible patients will have measurable or non-measurable, metastatic or unresectable, locally advanced breast cancer and may have received any number of prior therapies for their disease.

It is expected that the Phase I portion will enroll up to 20 patients and the Phase II portion will enroll up to 45 patients.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Indibulin
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 a Novel Indibulin Dosing Schedule for the Treatment of Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Ziopharm:

Primary Outcome Measures:
  • Phase I- Maximum Tolerated Dose [ Time Frame: Throughout Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    The primary objective of the Phase I portion of the trial is to determine the maximum tolerated dose (MTD) of Indibulin when given for 5 days followed by a 9 day rest (5—9) using a standard 3+3 dose escalation scheme for the treatment of metastatic breast cancer

  • Phase II- Progression Free Survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    The primary objective of the Phase II portion of this trial is to examine the efficacy of indibulin for the treatment of metastatic breast cancer at the MTD established in Phase I. The primary endpoint is the proportion of patients who are progression free at 4 months when treated with Indibulin (5-9)at the MTD determined by the phase I portion of the trial.


Secondary Outcome Measures:
  • Phase I- Number of participants with Adverse Events as a measure of safety and tolerability [ Time Frame: Duration of study, approximately one year ] [ Designated as safety issue: Yes ]
    To evaluate the safety of Indibulin when administered for 5 days followed by a 9 day rest (5-9) in patients with metastatic breast cancer

  • Phase I- Toxicity [ Time Frame: Cycle 1 (28 days), and duration of study (approximately one year) ] [ Designated as safety issue: Yes ]
    To describe the Cycle I and overall toxicity rates of indibulin (5-9) using the NCI CTC version 3.

  • Phase I- Pharmacokinetics of indibulin in study subject plasma assessed in Cycle 1 Day 1 and Cycle 1 Day 5 per schedule below in Description section. [ Time Frame: During Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
    To evaluate pharmacokinetics (PK) of Indibulin (5-9) as it is assessed in Cycle 1 Day 1, Day 2, Day 5 and Day 8. Cycle 1 PK schedule as follows: Day 1 immediately pre dose, 1 hour, 2 hours, 4 hours, 6 hours and approximately 24 hours after start of infusion (Cycle 2 Day 1), Day 5 pre-dose and at anytime during Day 8.

  • Phase II- Overall Response Rate [ Time Frame: At the end of Cycles 4 and 6 (approximately 4 months and 6 months respectively) ] [ Designated as safety issue: No ]
    To estimate the overall response rate (complete response and partial response)associated with Indibulin (5-9) schedule at eth MTD determined by the Phase I portion of this trial in patients with metastatic breast cancer.

  • Phase II- Rate of Stable Disease [ Time Frame: Phase II- greater than 6 months ] [ Designated as safety issue: No ]
    To estimate the rate of stable disease greater than 6 months associated with the Indibulin (5-9) schedule at the MTD determined by the the Phase I portion of this trial in patients with metastatic breast cancer.

  • Phase II- Number of patients with Adverse Events as a measure of safety and tolerability [ Time Frame: Throughout study, approximately one year ] [ Designated as safety issue: Yes ]
    To evaluate the safety of Indibulin when administered for 5 days followed by a 9 day rest (5-9) at the MTD determined by the Phase I portion of this trial in patients with metastatic breast cancer.


Estimated Enrollment: 60
Study Start Date: March 2010
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
open label, single arm, unblinded
Drug: Indibulin
Indibulin given orally once a day for 5 days followed by a 9 day rest
Other Names:
  • ZIO-301
  • Zybulin(TM)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic confirmation of invasive carcinoma of the breast.
  • Clinical evidence of metastatic disease or locally advanced disease not amenable to curative therapy.
  • Measurable or non-measurable lesions according to the RECIST Version 1.1 2009.
  • Any number of prior endocrine, biologic or chemotherapy regimens is permitted. All previous chemotherapy and biologic therapy must have been discontinued at least 3 weeks prior to beginning study drug. Endocrine therapy may not be used concurrently with protocol treatment. All acute toxic effects (excluding alopecia or neuropathy) of any prior therapy must have resolved to NCI CTC (version 4.0) Grade ≤ 1 or to baseline
  • Prior radiation therapy is permitted.
  • ECOG performance status of 0, 1 or 2.
  • Age ≥ 18 years
  • Life expectancy ≥ 12 weeks
  • Patients with HER2-positive (IHC 3+ or FISH-amplified) breast cancer must have received trastuzumab or have a contradiction to receiving HER2- targeted therapy (such as abnormal left ventricular ejection fraction)as determined by the treating physician.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:

    • Creatinine ≤ 1.5x upper limit of normal (ULN)
    • Total bilirubin ≤ 1.5x ULN
    • ALT or AST ≤ 2.5x ULN
    • ANC ≥ 1.5 x10(9)/L
    • Platelets ≥ 100 x10(9)/L
    • Hemoglobin ≥ 9g/dL
  • Subjects of childbearing potential must agree to use a barrier method of contraception throughout the study and for 3 months after study drug administration.

Exclusion Criteria:

  • Pregnant or nursing women may not participate.
  • Serious, uncontrolled, concurrent infection.
  • Patients with symptomatic CNS metastases that remain untreated by radiation therapy are excluded from this trial. The presence of asymptomatic, previously irradiated, stable brain metastases for at least 3 months are not grounds for trial exclusion.
  • Presence of uncontrolled gastrointestinal malabsorption syndrome.
  • Any chemotherapy, radiotherapy or breast cancer directed biologic therapy during the study or within 3 weeks of study start. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry. No washout period is required for hormonal therapies.
  • Concurrent radiation therapy is not permitted during treatment on protocol.
  • History of an invasive second primary malignancy diagnosed within the previous 3 years, except for Stage I endometrial or cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer.
  • Any medical, psychological or social condition that may interfere with the subject's ability to safely participate in the study.
  • Unwillingness to give written informed consent or unwillingness to participate or inability to comply with the protocol for the duration of the study. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures are necessary for participation in this clinical trial.
  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: NCT01113970

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
United States, Washington
Evergreen Hematology Oncology
Spokane, Washington, United States, 99218
Northwest Cancer Specialists
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Ziopharm
Memorial Sloan-Kettering Cancer Center
Investigators
Study Director: Jonathan J. Lewis, MD, PhD ZIOPHARM, Oncology, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Ziopharm
ClinicalTrials.gov Identifier: NCT01113970     History of Changes
Other Study ID Numbers: IBL2001
Study First Received: April 8, 2010
Last Updated: January 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ziopharm:
breast cancer
Indibulin
unresectable, locally advanced breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 16, 2014