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

NCT ID: NCT01728181

Last Updated: 2013-07-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2016-03-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I

Will receive Tivozanib and Erlotinib treatment.

Group Type: EXPERIMENTAL

Tivozanib

Intervention Type: 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.

Erlotinib

Intervention Type: DRUG

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

Phase II Group 1 (Standard of Care)

Group 1: VeriStrat® predicts the chance of no benefit from erlotinib

• The patient will get standard-of- care

Group Type: OTHER

Standard of Care treatment

Intervention Type: OTHER

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

Phase II Group 2 (arm 1)

Group 2: VeriStrat® predicts the chance of benefit from Erlotinib

• Arm 1: Patient will get the study drugs Erlotinib and Tivozanib

Group Type: ACTIVE_COMPARATOR

Tivozanib

Intervention Type: 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.

Erlotinib

Intervention Type: DRUG

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

Phase II Group 2 (arm 2)

Group 2: VeriStrat® predicts the chance of benefit from Erlotinib

• Arm 2: Patient will get the study drug erlotinib and placebo

Group Type: PLACEBO_COMPARATOR

Erlotinib

Intervention Type: DRUG

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

Interventions

Tivozanib

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.

Intervention Type: DRUG

Erlotinib

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

Intervention Type: DRUG

Standard of Care treatment

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

Intervention Type: OTHER

Other Intervention Names

AV-951; KRN951

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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)
• AST or ALT > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)
• Creatinine > 2.0 × ULN
• Proteinuria > 3+ by urinalysis or urine dipstick
• Non-healing wound, bone fracture, or skin ulcer.
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.
• Serious/active infection or infection requiring parenteral antibiotics.
• Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
• Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug, including but not limited to:

• Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
• Peripheral arterial ischemia > Grade 2 (per CTCAE Version 4.0)
• Significant bleeding disorders within 6 months prior to administration of first dose of study drug, including but not limited to:

• Hematemesis, hematochezia, melena or other gastrointestinal bleeding > Grade 2 (per CTCAE Version 4.0)
• Hemoptysis or other pulmonary bleeding (> 1/2 tsp/event over last 3 months not associated with bronchoscopy)
• Hematuria or other genitourinary bleeding > Grade 2 (per CTCAE Version 4.0)
• Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years.
• Pregnant or lactating females.
• History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant.
• Life-threatening illness or organ system dysfunction compromising safety evaluation.
• Requirement for hemodialysis or peritoneal dialysis.
• Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of tivozanib, major resection of the stomach or small bowel, or gastric bypass procedure.
• Psychiatric disorder or altered mental status precluding informed consent or protocol related testing.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

HCI59004

Identifier Type: -

Identifier Source: org_study_id