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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

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ClinicalTrials.gov Identifier: NCT00101348
Recruitment Status : Completed
First Posted : January 10, 2005
Last Update Posted : June 11, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE January 7, 2005
First Posted Date  ICMJE January 10, 2005
Last Update Posted Date June 11, 2014
Study Start Date  ICMJE January 2005
Actual Primary Completion Date October 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2013)
  • 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) [ Time Frame: 28 days ]
    The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
  • MTD of bevacizumab combined with cetuximab and erlotinib hydrochloride determined by DLT graded according to the CTCAE version 3 (Part II) [ Time Frame: 28 days ]
    The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00101348 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2013)
  • Antitumor activity defined as the number and extent (complete or partial) objective responses as well as objective stable disease as measured by RECIST criteria [ Time Frame: 6 months ]
    The estimated rate and their 95% confidence interval, will be reported.
  • Median time to progression [ Time Frame: Up to 1 month ]
  • Progression-free survival [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma
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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: erlotinib hydrochloride
    Given orally
    Other Names:
    • CP-358,774
    • erlotinib
    • OSI-774
  • Biological: cetuximab
    Given IV
    Other Names:
    • C225
    • C225 monoclonal antibody
    • IMC-C225
    • MOAB C225
    • monoclonal antibody C225
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE 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 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.

Interventions:
  • Drug: erlotinib hydrochloride
  • Biological: cetuximab
  • Biological: bevacizumab
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2007)
66
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2008
Actual Primary Completion Date October 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00101348
Other Study ID Numbers  ICMJE NCI-2012-02639
NCI-2012-02639 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000401514
NCI-6588
CTRC-IDD-0332 ( Other Identifier: Cancer Therapy and Research Center at The UT Health Science Center at San Antonio )
6588 ( Other Identifier: CTEP )
U01CA069853 ( U.S. NIH Grant/Contract )
P30CA054174 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alain Mita Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
PRS Account National Cancer Institute (NCI)
Verification Date December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP