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

NCT01113970 | Unknown Phase 1

• 1 other identifier: IBL2001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; Indibulin; unresectable, locally advanced breast cancer

Outcome Measures

Primary Outcomes (2)

• Phase I- Maximum Tolerated Dose

  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

  Throughout Cycle 1 (28 days)

• Phase II- Progression Free Survival

  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.

  4 months

Secondary Outcomes (6)

• Phase I- Number of participants with Adverse Events as a measure of safety and tolerability

  Duration of study, approximately one year

• Phase I- Toxicity

  Cycle 1 (28 days), and duration of study (approximately one year)

• 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.

  During Cycle 1 (28 days)

• Phase II- Overall Response Rate

  At the end of Cycles 4 and 6 (approximately 4 months and 6 months respectively)

• Phase II- Rate of Stable Disease

  Phase II- greater than 6 months

Study Arms (1)

Single Arm

EXPERIMENTAL

open label, single arm, unblinded

Drug: Indibulin

Interventions

Indibulin DRUG

Indibulin given orally once a day for 5 days followed by a 9 day rest

Also known as: ZIO-301, Zybulin(TM)

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnant or nursing women may not participate.
• Serious, uncontrolled, concurrent infection.
• 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.

Sponsors & Collaborators

• Alaunos Therapeutics: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (4)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Evergreen Hematology Oncology

Spokane, Washington, 99218, United States

Location

Northwest Cancer Specialists

Vancouver, Washington, 98684, United States

Location

Related Publications (1)

• Kapoor S, Srivastava S, Panda D. Indibulin dampens microtubule dynamics and produces synergistic antiproliferative effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy. Sci Rep. 2018 Aug 17;8(1):12363. doi: 10.1038/s41598-018-30376-y.

  PMID: 30120268 DERIVED

Related Links

• ZIOPHARM Oncology, Inc. home page

MeSH Terms

Conditions

Breast Neoplasms

Interventions

indibulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jonathan J. Lewis, MD, PhD

  ZIOPHARM, Oncology, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2010
• First Posted: April 30, 2010
• Study Start: March 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 30, 2013

Record last verified: 2012-07

Locations

US (4)