Phase 1b Study of Indibulin in Combination With Capecitabine in Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00726687
Recruitment Status : Unknown
Verified July 2012 by Ziopharm.
Recruitment status was:  Active, not recruiting
First Posted : August 1, 2008
Last Update Posted : July 19, 2012
Information provided by (Responsible Party):

Brief Summary:
This is a phase 1b study of Indibulin in combination with Capecitabine in advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: indibulin Drug: capecitabine Phase 1 Phase 2

Detailed Description:

The primary objective of the trial is to determine the maximum tolerated dose (MTD) and optimal dosing schedule of indibulin in combination with capecitabine in subjects diagnosed as having advanced solid tumors.

Secondary objectives include the determination of dose-limiting toxicity (DLT), safety and tolerability, and preliminary activity of this combination. In addition, biological activity of indibulin in combination with capecitabine will be evaluated.

Single arm, open label, Phase Ib, dose-escalation study of indibulin in combination with capecitabine in subjects with advanced histologically confirmed, solid tumors for which no standard therapy exists and for whom treatment with capecitabine is considered medically acceptable.

3 subjects will be treated at each dose level. When DLT occurs in 2 or more of 6 or fewer subjects, MAD has been reached and the dose will be reduced to the previous dosing level, which will be considered the MTD.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b Study of Indibulin in Combination With Capecitabine in Advanced Solid Tumors
Study Start Date : June 2008
Estimated Primary Completion Date : June 2013
Estimated Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: single
Single arm designed to elicit Maximum Tolerated Dose
Drug: indibulin
indibulin, dose escalation, 400-600 mg taken twice every day
Drug: capecitabine
capecitabine, dose escalation, 875 mg/m2- 1250 mg/m2, taken twice daily for 14 days per 21 day cycle
Other Name: Xeloda

Primary Outcome Measures :
  1. toxicities [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. pharmacokinetics [ Time Frame: 6 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  1. Subjects with advanced, histologically confirmed solid tumors for whom treatment with capecitabine is considered medically acceptable
  2. ≥18 years of age
  3. ECOG performance score ≤2 (see Appendix 2)
  4. Eligible subjects MUST have at least one measurable lesion as defined by RECIST guidelines (see Appendix 3). Measurable lesions MUST NOT have been in a previously irradiated field or injected with biological agents.
  5. Life-expectancy ≥12 weeks
  6. No more than 2 prior chemotherapy regimens for metastatic disease
  7. Subjects on prophylactic anticoagulation (i.e., low-dose warfarin) are eligible provided the coagulation parameter levels are as follows: prothrombin time (INR of prothrombin time) <1.1× institutional ULN
  8. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted <2 weeks prior to Study Day 1:

    • Creatinine ≤1.5 × upper limit of normal (ULN) OR a calculated creatinine clearance ≥1.50 cc/min (See Appendix 6 for calculation method)
    • Total bilirubin ≤1.5×ULN
    • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤2.5×ULN (<5×ULN for patients presenting with liver involvement)
    • White blood cell count ≥3.0×109/L
    • Absolute neutrophil count (ANC) ≥1.5×109/L
    • Platelets ≥100×109/L
    • Hemoglobin ≥10 g/dL
  9. Written informed consent in compliance with ZIOPHARM policies and the Institutional Review Board (IRB) having jurisdiction over the site
  10. Ability and willingness to undergo multiple venous punctures for serum PK sampling
  11. For the second phase of the trial (expanded cohort of 10), only capecitabine-naïve subjects will be included; prior therapy with 5-FU will be allowed
  12. Each man and woman of childbearing potential must agree to use a reliable method of contraception during the study and for 3 months following his or her last dose of study drug

Exclusion Criteria

  1. New York Heart Association (NYHA) functional class ≥3 or myocardial infarction within 6 months (see Appendix 4)
  2. Severe renal impairment (creatinine clearance below 30 mL/min)
  3. Known dihydropyrimidine dehydrogenase deficiency (DPD)
  4. Any evidence of bleeding diathesis or coagulopathy
  5. International normalized ration (INR) >1.5, unless the subject is on full-dose warfarin
  6. Subjects on full-dose anticoagulants (e.g., warfarin) are eligible provided that both of the following criteria are met:

    • The subject must have an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular-weight heparin
    • The subject must not have any active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  7. Pregnancy and/or lactation. To be enrolled, each woman of childbearing potential must have a negative pregnancy test, which will be repeated at the end of the study.
  8. Uncontrolled systemic infection (documented with microbiological studies)
  9. Anticancer chemotherapy or immunotherapy within 4 weeks of study entry or at any time during the study or investigational drug therapy outside of this trial during or within 4 weeks of study entry
  10. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry.
  11. Radiotherapy within 3 weeks of study entry or at any time during the study. For target lesions that have been radiated within 3 months of study entry, only those lesions with documented progression post radiation will be allowed.
  12. Surgery within 4 weeks of start of study drug dosing, excluding tumor biopsy for pharmacodynamic parameters
  13. History of an invasive second primary malignancy diagnosed within the previous 3 years except for Stage I endometrial/cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer
  14. Substance abuse or medical, psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of study results
  15. Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance with study protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00726687

United States, Indiana
Indianapolis, Indiana, United States
United States, Nevada
Las Vegas, Nevada, United States
United States, Washington
Vancouver, Washington, United States
Sponsors and Collaborators
Study Chair: Jonathan Lewis, MD Ziopharm

Responsible Party: Ziopharm Identifier: NCT00726687     History of Changes
Other Study ID Numbers: IBL1005
First Posted: August 1, 2008    Key Record Dates
Last Update Posted: July 19, 2012
Last Verified: July 2012

Keywords provided by Ziopharm:

Additional relevant MeSH terms:
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents