Phase I Study of Indibulin in Combination With Erlotinib in Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

Phase I Study of Indibulin in Combination With Erlotinib in Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00591383
• Other study ID #: IBL1004
• Status: Active, not recruiting
• Phase: Phase 1
• First received: December 26, 2007
• Last updated: July 18, 2012
• Start date: January 2008
• Est. completion date: June 2013

Study information

• Verified date: July 2012
• Source: Ziopharm
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subjects with advanced, histologically confirmed solid tumors for which no standard therapy exists and for whom treatment with erlotinib is considered medically acceptable.

2. =18 years of age

3. ECOG performance score =2

4. Eligible subjects MUST have at least one measurable lesion as defined by RECIST guidelines. 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. 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 =50 cc/min

• Total bilirubin =1.5×ULN

• Alanine transaminase (ALT) and aspartate transaminase (AST) =2.5×ULN

• White blood cell count =3.0×109/L

• Absolute Neutrophil Count (ANC) =1.5×109/L

• Platelets =100×109/L

• Hemoglobin =10 g/dL

8. Written informed consent in compliance with ZIOPHARM policies and the Human Investigation Review Committee with jurisdiction over the site.

9. Each man and woman of childbearing potential must agree to use a reliable method of contraception during the study and for 3 months following the last dose of study drug.

Exclusion Criteria:

1. New York Heart Association (NYHA) functional class =3 or myocardial infarction within 6 months (see Appendix 5)

2. Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation

3. Subjects cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs: eg, phenytoin, carbamazepine, phenobarbital, primidone, oxcarbezine)

4. Subjects may not be taking CYP3A4 inducers (rifampicin)

5. Subjects must not have any evidence of bleeding diathesis or coagulopathy

6. Subjects with international normalized ration (INR) >1.5 are excluded, unless the subject is on full dose warfarin

7. Subjects on full-dose anticoagulants (eg, warfarin) are eligible provided that both of the following criteria are met:

• The subject has 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 has no active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices.

8. Subjects on prophylactic anticoagulation (ie, low-dose warfarin) are eligible provided their coagulation parameter levels are as follows: prothrombin time (INR of prothrombin time) <1.1×institutional ULN

9. Pregnancy and/or lactation

10. Uncontrolled systemic infection (documented with microbiological studies)

11. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry. Mitomycin C or nitrosureas should not be given within 6 weeks of study entry.

12. Prior treatment with EGFR inhibitors

13. Radiotherapy during the study or within 3 weeks of study entry

14. Surgery within 4 weeks of start of study drug excluding tumor biopsy for pharmacodynamic parameters

15. Investigational drug therapy outside of this trial during or within 4 weeks of study entry

16. 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

17. Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results

18. Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance with the study protocol

Study Design

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

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• indibulin
indibulin, dose escalation, 200 mg - 600 mg. Taken twice every day.
• erlotinib
erlotinib taken at 150 mg every morning with food.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ziopharm

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	toxicities		6 months	Yes
Secondary	pharmacokinetics		6 months	No