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

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: indibulin
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with advanced, histologically confirmed solid tumors for which no standard therapy exists and for whom treatment with erlotinib is considered medically acceptable. ≥18 years of age ECOG performance score ≤2 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. Life-expectancy ≥12 weeks No more than 2 prior chemotherapy regimens for metastatic disease 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 Written informed consent in compliance with ZIOPHARM policies and the Human Investigation Review Committee with jurisdiction over the site. 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: New York Heart Association (NYHA) functional class ≥3 or myocardial infarction within 6 months (see Appendix 5) Uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation Subjects cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs: eg, phenytoin, carbamazepine, phenobarbital, primidone, oxcarbezine) Subjects may not be taking CYP3A4 inducers (rifampicin) Subjects must not have any evidence of bleeding diathesis or coagulopathy Subjects with international normalized ration (INR) >1.5 are excluded, unless the subject is on full dose warfarin 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. 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 Pregnancy and/or lactation Uncontrolled systemic infection (documented with microbiological studies) 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. Prior treatment with EGFR inhibitors Radiotherapy during the study or within 3 weeks of study entry Surgery within 4 weeks of start of study drug excluding tumor biopsy for pharmacodynamic parameters Investigational drug therapy outside of this trial during or within 4 weeks of study entry 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 Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance with the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Once Maximum Tolerated Dose (MTD) is determined an expanded cohort will be enrolled to evaluate efficacy. | Drug: indibulin<br>* indibulin, dose escalation, 200 mg - 600 mg. Taken twice every day.<br>* Other names: ZIO-301;Drug: erlotinib<br>* erlotinib taken at 150 mg every morning with food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| toxicities |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Indibulin, Erlotinib