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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Advanced Solid Tumors

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Trial Information

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

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

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.

Inclusion Criteria

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Jonathan Lewis, MD

Investigator Role:

Study Chair

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

June 2013

Related Keywords:

  • Advanced Solid Tumors
  • Cancer
  • Indibulin
  • Capecitabine
  • Xeloda
  • Neoplasms



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Indianapolis, Indiana  
Las Vegas, Nevada  89109