Erlotinib And Cetuximab With Or Without Bevacizumab In Treating Patients With Metastatic Or Unresectable Kidney, Colorectal, Head And Neck, Pancreatic, Or Non-Small Cell Lung Cancer

Study Overview

Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer

This randomized phase I/II trial studies the side effects, best way to give, and best dose of erlotinib and bevacizumab when given with cetuximab and how well giving erlotinib and cetuximab together with or without bevacizumab works in treating patients with metastatic or unresectable kidney, colorectal, head and neck, pancreatic, or non-small cell lung cancer. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with cetuximab and/or bevacizumab may kill more tumor cells.

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of erlotinib when combined with cetuximab in patients with metastatic or unresectable renal cell, colorectal, head and neck, pancreatic, or non-small cell lung cancer (part 1). II. Determine the MTD of bevacizumab when combined with cetuximab and erlotinib in these patients (part 2). III. Determine the toxic effects, both quantitatively and qualitatively, of these regimens in these patients. IV. Determine the antitumor activity of these regimens, in terms of tumor response, short-term survival, and progression-free survival, in these patients. SECONDARY OBJECTIVES: I. Compare, preliminarily, the toxicity and antitumor activity profiles of these regimens in these patients. OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib and bevacizumab. Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Part 2: Patients receive erlotinib as in part 1 at the MTD and cetuximab as in part 1. Patients also receive bevacizumab IV over 1½ hours on day 1 and over 1 hour on day 15. Cohorts of 3-6 patients receive escalating doses of bevacizumab until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. In both groups, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. After completion of study treatment, patients are followed at 1 month.

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Colon Cancer
Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Lymphoepithelioma of the Oropharynx
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Non-small Cell Lung Cancer
Recurrent Pancreatic Cancer
Recurrent Rectal Cancer
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Stage III Adenoid Cystic Carcinoma of the Oral Cavity
Stage III Basal Cell Carcinoma of the Lip
Stage III Colon Cancer
Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Lymphoepithelioma of the Oropharynx
Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage III Mucoepidermoid Carcinoma of the Oral Cavity
Stage III Pancreatic Cancer
Stage III Rectal Cancer
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IIIB Non-small Cell Lung Cancer
Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
Stage IV Basal Cell Carcinoma of the Lip
Stage IV Colon Cancer
Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Lymphoepithelioma of the Oropharynx
Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
Stage IV Non-small Cell Lung Cancer
Stage IV Pancreatic Cancer
Stage IV Rectal Cancer
Stage IV Renal Cell Cancer
Stage IV Salivary Gland Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Untreated Metastatic Squamous Neck Cancer With Occult Primary

DRUG: erlotinib hydrochloride
BIOLOGICAL: cetuximab
BIOLOGICAL: bevacizumab
OTHER: laboratory biomarker analysis

NCI-2012-02639
NCI-2012-02639 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CDR0000401514
NCI-6588
CTRC-IDD-0332 (OTHER Identifier) (OTHER: Cancer Therapy and Research Center at The UT Health Science Center at San Antonio)
6588 (OTHER Identifier) (OTHER: CTEP)
U01CA069853 (U.S. NIH Grant/Contract)
P30CA054174 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-01-07	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-06-10
First Submitted that Met QC Criteria 2005-01-07	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-06-11
First Posted (ESTIMATED) 2005-01-10	Results First Posted N/A	Last Verified 2012-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (erlotinib hydrochloride, cetuximab, bevacizumab) Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dos	DRUG: erlotinib hydrochloride Given orally BIOLOGICAL: cetuximab Given IV BIOLOGICAL: bevacizumab Given IV OTHER: laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)

Part 1: Patients receive oral erlotinib once daily on days 1-28. Patients also receive cetuximab IV over 3 hours on day 1 and over 1 hour on days 8, 15, and 22. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dos

DRUG: erlotinib hydrochloride

Given orally

BIOLOGICAL: cetuximab

Given IV

BIOLOGICAL: bevacizumab

Given IV

OTHER: laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose (MTD) of erlotinib hydrochloride combined with cetuximab determined by dose-limiting toxicities (DLT) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3 (Part I)	The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.	28 days
MTD of bevacizumab combined with cetuximab and erlotinib hydrochloride determined by DLT graded according to the CTCAE version 3 (Part II)	The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.	28 days

Secondary Outcome Measures	Measure Description	Time Frame
Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria	The estimated rate and their 95% confidence interval, will be reported.	6 months
Median time to progression		Up to 1 month
Progression-free survival		From the start of the treatment until the date the criteria for progression are met or the date the patient is taken off study for any reason, assessed up to 1 month

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

One of the following histologically confirmed diagnoses:

Renal cell cancer

Clear cell histology
Metastatic or unresectable disease AND meets 1 of the following criteria:

Recurrent disease
Refractory to interleukin-2 (IL-2)- or interferon-based therapy
Previously untreated AND not a candidate for IL-2-based therapy
Colorectal, head and neck, pancreatic, or non-small cell lung cancer

Metastatic or unresectable disease
Progression after prior standard treatment
No evidence of CNS disease, including the following (part 2 only):

Primary brain tumor
Brain metastases
Paraffin embedded tumor blocks available
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 12 weeks
Absolute neutrophil count ≥ 1,500 mm^3
Platelet count ≥ 100,000 mm^3
Bilirubin ≤ 1.5 mg/dL
AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is present)
PTT and INR ≤ 1.5, unless receiving full-dose warfarin (part 2 only)
Creatinine ≤ 1.5 times ULN
Creatinine clearance ≥ 60 mL/min
Calcium < 10 mg/dL (hypocalcemic agents allowed)
No proteinuria*
Protein < 1 g on 24-hour urine collection*
No unstable angina pectoris
No cardiac arrhythmia
No symptomatic congestive heart failure
None of the following are allowed for part 2:

Myocardial infarction within the past 6 months
New York Heart Association class II-IV heart disease
Serious cardiac arrhythmia requiring medication
Peripheral vascular disease ≥ grade II
Recent history of cerebrovascular accident
Uncontrolled hypertension (blood pressure ≥ 150/85 mm Hg despite medication)
Other clinically significant cardiovascular disease
No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
No GI tract disease resulting in a requirement for IV alimentation
No active peptic ulcer disease
No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (part 2 only)
No ongoing or active infection
No active infection requiring parenteral antibiotics (part 2 only)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 2 months after study treatment
No significant traumatic injury within the past 28 days (part 2 only)
No history of abnormalities of the cornea (e.g., dry eye syndrome, Sjögren's syndrome, or congenital abnormality [e.g., Fuch's dystrophy])
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast or cervix
No psychiatric illness or social situation that would preclude study compliance
No serious or non-healing wound ulcer or bone fracture (part 2 only)
No other uncontrolled illness
See Disease Characteristics
More than 4 weeks since prior immunotherapy
No prior cetuximab
No prior bevacizumab
Concurrent epoetin alfa or darbepoetin alfa allowed
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
More than 4 weeks since prior radiotherapy
No prior surgical procedures affecting absorption
Prior nephrectomy or resection of metastatic lesions allowed provided patient has fully recovered
More than 7 days since prior core biopsy*
More than 28 days since prior major surgery or open biopsy*
No concurrent major surgery*
Recovered from all prior therapy
No prior erlotinib
Concurrent bisphosphonates allowed
Concurrent full-dose anticoagulants allowed provided the following criteria are met (part 2 only):

In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin
No active bleeding
No pathological conditions that carry a high risk of bleeding (e.g., tumor involving major vessels or varices)
No other concurrent investigational agents
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent anticancer therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Alain Mita, Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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