Avastin and Tarceva for Locally Advanced or Metastatic Non-Squamous Non-Small-Cell Lung Cancer

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00043823

Collaborator

Genentech, Inc. (Industry), Vanderbilt-Ingram Cancer Center (Other)

Enrollment

Locations

Arm

45.4

Actual Duration (Months)

20.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objectives:

(Phase I) To establish the maximum tolerated dose and dose-limiting toxicities of the combination of OSI-774 (Tarceva™) and rhuMAb VEGF (Avastin™) in patients with advanced Non-small-cell lung carcinoma (NSCLC).
(Phase II) To assess response rate and tolerability of the regimen at the dose level established in the phase I portion of this study.

Secondary Objectives:

(Phase I and II) To evaluate the pharmacokinetic interaction between the combination.
(Phase I) To establish a phase II regimen of the OSI-774/ rhuMAb VEGF combination, for further study alone or in combination with cytotoxic chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Avastin Drug: Tarceva	Phase 1/Phase 2

Detailed Description

Patients will be treated with oral Tarceva daily for 21 days each cycle. Patients will receive Avastin by IV on day 1 of each 21-day cycle. If a patient has no grade 3 or 4 toxicities after the 1st cycle, then the patient may continue the same doses of Tarceva and Avastin for another cycle. If the patient has response or stable disease after 6 weeks (2 cycles), the patient may continue on the same doses of Tarceva and Avastin. A patient may receive treatment on this study for up to one year, unless his or her disease progresses or side effects become too severe.

The starting dose is 100 mg daily of Tarceva and 7.5 mg/kg every 21 days of Avastin.

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety and Efficacy of Recombinant Humanized Monoclonal Anti-VEGF Antibody rhuMAb VEGF and EGFR Tyrosine Kinase Inhibitor OSI-774 for Locally Advanced or Metastatic Non-Squamous Cell NSCLC in Patients Who Have Been Previously Treated

Actual Study Start Date :

Aug 1, 2002

Actual Primary Completion Date :

May 15, 2006

Actual Study Completion Date :

May 15, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avastin + Tarceva Combination Therapy (Avastin + Tarceva) = Avastin IV Day 1 of each 21-day cycle + oral Tarceva daily.	Drug: Avastin 7.5 mg/kg By Vein on Day 1 of Every 21 Day Cycle Other Names: rhuMAb VEGF Bevacizumab Anti-VEGF monoclonal antibody Drug: Tarceva 100 mg By Mouth Daily for 3 Weeks Other Names: OSI-774 Erlotinib Hydrocholoride

Arm

Intervention/Treatment

Experimental: Avastin + Tarceva

Combination Therapy (Avastin + Tarceva) = Avastin IV Day 1 of each 21-day cycle + oral Tarceva daily.

Drug: Avastin

7.5 mg/kg By Vein on Day 1 of Every 21 Day Cycle

Other Names:

rhuMAb VEGF

Bevacizumab

Anti-VEGF monoclonal antibody

Drug: Tarceva

100 mg By Mouth Daily for 3 Weeks

Other Names:

OSI-774

Erlotinib Hydrocholoride

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of Tarceva in combination with Avastin [After each 21 day cycle]

Secondary Outcome Measures

Response in Patients With NSCLC Receiving Combination Avastin and Tarceva [6 weeks (2 cycles)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient has histologically proven stage IIIB with pleural effusion, stage IV or recurrent non-squamous NSCLC.
Patient has a Karnofsky performance status >=70%.
Patient has adequate bone marrow function: WBC >= 3,000 cells/mm3, ANC >= 1,500 cells/mm3, platelet count >= 100,000 cells/mm3, Hgb >= 9.0 g/dL.
Patient has adequate liver function: total bilirubin level <= 2.0 mg/dL, albumin >= 2.5 g/dL.
Transaminases (aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT)) and alkaline phosphatase may be up to 2.5 x ULN.
Patient has adequate renal function: a serum creatinine < 2 mg/dl
Patient has signed a written informed consent.
Patient has received at least one prior chemotherapeutic regimen for recurrent or metastatic disease.

Exclusion Criteria:

Patient has not received prior chemotherapeutic regimens for advanced disease.
Patient has received prior biologic therapy targeting epidermal growth factor receptor (EGFR) and/or Vascular endothelial growth factor (VEGF).
Patient has received radiation therapy within the past 3 weeks.
Patient has signs or symptoms of acute infection requiring systemic therapy.
Patient exhibits confusion, disorientation, or has a history of major psychiatric illness that may impair patient's understanding of the informed consent.
Patient requires total parenteral nutrition with lipids.
Patient has a history of uncontrolled heart disease and/or uncontrolled hypertension (> 150/100 mmHg).
Because of the possible teratogenic effect, pregnant women and women who are currently breast-feeding may not participate in this study. - All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.
Serious infection or other intercurrent illness requiring immediate therapy.
Clinical/imaging evidence of Central Nervous System (CNS) malignancy or with recently treated CNS malignancy, as well as those experiencing recent cerebrovascular accident (CVA), or other CNS bleeding.
Pediatric patients in whom open growth plates would be expected.
Urine protein qualitative value of > 30 in urinalysis or > +1 in proteinuria testing by dipstick.
Patient has a clinical history of coagulopathy or thrombosis.
Patient is currently receiving or intending to receive anti-coagulants.
Patient has had a recent myocardial infarction (still inside the healing period). Note: a six-month window is optimal.
Patient is recovering from recent major surgery (e.g., less than 2 weeks since surgery) or is anticipating major surgery.
Patient has a clinical history of hemoptysis or hematemesis.
Patient may not have percutaneous endoscopic gastrostomy (PEG) or gastrostomy (G) tube.