A Phase I/II Study of Tivozanib and Erlotinib as Initial Treatment for Metastatic Non-small Cell Lung Cancer Assigned by VeriStrat® Serum Proteomic Evaluation

NCT01728181 | Withdrawn Phase 1 DMC

• 1 other identifier: HCI59004
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The current trial "A Phase I/II study of Erlotinib +/- Tivozanib as initial treatment for Metastatic Non-small Cell Lung Cancer assigned by VeriStrat® Serum Proteomic Evaluation" will begin by evaluating toxicity for the combination of Tivozanib and Erlotinib to determine a phase II dose. The phase II portion of the study will seek to duplicate the finding of the BEER trial in a selected population of patients with NSCLC with a VeriStrat® Good signature using two oral agents with Tivozanib substituted for bevacizumab. Phase II will be designed as a selection-based randomized trial. Patients with VeriStrat® Good signature will be assigned to EGFR inhibitor therapy with a randomization to Erlotinib plus/minus Tivozanib. Patients with VeriStrat® Poor signature will be assigned to standard of care. Standard-of-care chemotherapy as first treatment at the discretion of patient and physician will be evaluated for response to treatment, survival and repeat VeriStrat® signature.

Conditions

Non-small Cell Lung Cancer; Stage IV Disease; EGFR Unknown or Wild-type

Outcome Measures

Primary Outcomes (2)

• Safety of combination tivozanib and erlotinib

  Phase I- To define the safety (maximum tolerated dose) of Tivozanib when administered in combination with Erlotinib in patients with NSCL cancer.

  36 months

• Overall Survival

  Phase II - Overall survival for selection strategy of Erlotinib +/- Tivozanib

  36 months

Secondary Outcomes (1)

• Overall Survival for entire population

  36 months

Study Arms (4)

Phase I

EXPERIMENTAL

Will receive Tivozanib and Erlotinib treatment.

Drug: Tivozanib; Drug: Erlotinib

Phase II Group 1 (Standard of Care)

OTHER

Group 1: VeriStrat® predicts the chance of no benefit from erlotinib • The patient will get standard-of- care

Other: Standard of Care treatment

Phase II Group 2 (arm 1)

ACTIVE COMPARATOR

Group 2: VeriStrat® predicts the chance of benefit from Erlotinib • Arm 1: Patient will get the study drugs Erlotinib and Tivozanib

Drug: Tivozanib; Drug: Erlotinib

Phase II Group 2 (arm 2)

PLACEBO COMPARATOR

Group 2: VeriStrat® predicts the chance of benefit from Erlotinib • Arm 2: Patient will get the study drug erlotinib and placebo

Drug: Erlotinib

Interventions

Tivozanib DRUG

The phase I study will test two dose levels of tivozanib (dose level 1: 1.0 mg and dose level 2: 1.5 mg) given daily for 3 consecutive weeks followed by one week break. Based on the phase I results, the dose of tivozanib will be chosen for the phase II study.

Also known as: AV-951, KRN951

Phase I; Phase II Group 2 (arm 1)

Erlotinib DRUG

150 mg/day for 28 day cycle. No rest period.

Phase I; Phase II Group 2 (arm 1); Phase II Group 2 (arm 2)

Standard of Care treatment OTHER

This treatment will be determined by the study doctor and is considered standard of care.

Phase II Group 1 (Standard of Care)

Eligibility Criteria

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

You may qualify if:

• Histological or cytological diagnosis of non-squamous, non-small cell lung cancer.
• Stage IV disease.
• Age \> 18
• If female and of childbearing potential, documentation of negative pregnancy test within 7 days prior to first dose.
• Sexually active women of childbearing potential must agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug. All fertile female subjects (and their partners) must agree to use a highly effective method of contraception. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study).
• Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
• No prior treatment for metastatic disease (Phase II ONLY). Patients who received adjuvant systemic chemotherapy are eligible if greater than 6 months has elapsed.
• Prior erlotinib treatment is allowed in phase I.
• Performance status of 0-1.
• One disease site meeting RECIST (version 1.1) criteria for measurable or non-measurable disease. Disease sites measured from the CT portion of a combined PET/CT may be used to document measurable disease (Liver or PET findings may be used only for non-measurable disease).

You may not qualify if:

• Significant cardiovascular disease, including:
• Active, clinically symptomatic left ventricular failure.
• Uncontrolled hypertension: Systolic blood pressure of \>140 mmHg or diastolic blood pressure of \>90 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart.
• Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug.
• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
• Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
• Coronary or peripheral artery bypass graft within 6 months of screening.
• Uncontrolled CNS metastases are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been treated, toxicity of radiation has resolved and steroids are no longer required. Leptomeningeal metastases are not allowed.
• Any of the following hematologic abnormalities:
• Hemoglobin \< 9.0 g/dL
• Absolute neutrophil count (ANC) \< 1500 per mm3
• Platelet count \< 100,000 per mm3
• INR \>1.5 or PTT \>1.5 × ULN
• Any of the following serum chemistry abnormalities:
• Total bilirubin \> 1.5 × ULN (or \> 2.5 × ULN for subjects with Gilbert's syndrome)

Sponsors & Collaborators

• University of Utah: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Disease

Interventions

tivozanib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 16, 2012
• Study Start: November 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: July 25, 2013

Record last verified: 2013-07