NCT00101348

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
66

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2005

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2005

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

January 7, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 10, 2005

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2007

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2008

Completed
Last Updated

June 11, 2014

Status Verified

December 1, 2012

Enrollment Period

2.7 years

First QC Date

January 7, 2005

Last Update Submit

June 10, 2014

Conditions

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell CarcinomaRecurrent Adenoid Cystic Carcinoma of the Oral CavityRecurrent Basal Cell Carcinoma of the LipRecurrent Colon CancerRecurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal CavityRecurrent Inverted Papilloma of the Paranasal Sinus and Nasal CavityRecurrent Lymphoepithelioma of the NasopharynxRecurrent Lymphoepithelioma of the OropharynxRecurrent Metastatic Squamous Neck Cancer With Occult PrimaryRecurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal CavityRecurrent Mucoepidermoid Carcinoma of the Oral CavityRecurrent Non-small Cell Lung CancerRecurrent Pancreatic CancerRecurrent Rectal CancerRecurrent Salivary Gland CancerRecurrent Squamous Cell Carcinoma of the HypopharynxRecurrent Squamous Cell Carcinoma of the LarynxRecurrent Squamous Cell Carcinoma of the Lip and Oral CavityRecurrent Squamous Cell Carcinoma of the NasopharynxRecurrent Squamous Cell Carcinoma of the OropharynxRecurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal CavityRecurrent Verrucous Carcinoma of the LarynxRecurrent Verrucous Carcinoma of the Oral CavityStage III Adenoid Cystic Carcinoma of the Oral CavityStage III Basal Cell Carcinoma of the LipStage III Colon CancerStage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal CavityStage III Inverted Papilloma of the Paranasal Sinus and Nasal CavityStage III Lymphoepithelioma of the NasopharynxStage III Lymphoepithelioma of the OropharynxStage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal CavityStage III Mucoepidermoid Carcinoma of the Oral CavityStage III Pancreatic CancerStage III Rectal CancerStage III Salivary Gland CancerStage III Squamous Cell Carcinoma of the HypopharynxStage III Squamous Cell Carcinoma of the LarynxStage III Squamous Cell Carcinoma of the Lip and Oral CavityStage III Squamous Cell Carcinoma of the NasopharynxStage III Squamous Cell Carcinoma of the OropharynxStage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal CavityStage III Verrucous Carcinoma of the LarynxStage III Verrucous Carcinoma of the Oral CavityStage IIIB Non-small Cell Lung CancerStage IV Adenoid Cystic Carcinoma of the Oral CavityStage IV Basal Cell Carcinoma of the LipStage IV Colon CancerStage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal CavityStage IV Inverted Papilloma of the Paranasal Sinus and Nasal CavityStage IV Lymphoepithelioma of the NasopharynxStage IV Lymphoepithelioma of the OropharynxStage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal CavityStage IV Mucoepidermoid Carcinoma of the Oral CavityStage IV Non-small Cell Lung CancerStage IV Pancreatic CancerStage IV Rectal CancerStage IV Renal Cell CancerStage IV Salivary Gland CancerStage IV Squamous Cell Carcinoma of the HypopharynxStage IV Squamous Cell Carcinoma of the LarynxStage IV Squamous Cell Carcinoma of the Lip and Oral CavityStage IV Squamous Cell Carcinoma of the NasopharynxStage IV Squamous Cell Carcinoma of the OropharynxStage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal CavityStage IV Verrucous Carcinoma of the LarynxStage IV Verrucous Carcinoma of the Oral CavityUntreated Metastatic Squamous Neck Cancer With Occult Primary

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (3)

  • Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria

    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

Study Arms (1)

Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)

EXPERIMENTAL

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.

Drug: erlotinib hydrochlorideBiological: cetuximabBiological: bevacizumabOther: laboratory biomarker analysis

Interventions

Given orally

Also known as: CP-358,774, erlotinib, OSI-774
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
cetuximabBIOLOGICAL

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)
bevacizumabBIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)

Correlative studies

Treatment (erlotinib hydrochloride, cetuximab, bevacizumab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +61 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Colonic NeoplasmsEsthesioneuroblastoma, OlfactoryCarcinoma, Non-Small-Cell LungPancreatic NeoplasmsRectal NeoplasmsSalivary Gland NeoplasmsSquamous Cell Carcinoma of Head and NeckCarcinoma, Renal Cell

Interventions

Erlotinib HydrochlorideCetuximabBevacizumab

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesNeuroblastomaNeuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueOlfactory Nerve DiseasesCranial Nerve DiseasesNervous System DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System DiseasesRectal DiseasesMouth NeoplasmsHead and Neck NeoplasmsMouth DiseasesStomatognathic DiseasesSalivary Gland DiseasesCarcinoma, Squamous CellCarcinomaAdenocarcinomaKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

QuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Alain Mita

    Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2005

First Posted

January 10, 2005

Study Start

January 1, 2005

Primary Completion

October 1, 2007

Study Completion

May 1, 2008

Last Updated

June 11, 2014

Record last verified: 2012-12

Locations