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A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma


Phase 1
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

A Phase I, and Biologic Correlative Study of Erlotinib, in Combination With Cetuximab and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Description:

The occurrence and maximal grade of toxicity for the whole duration of treatment will be listed and tabulated by type.

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Alain Mita

Investigator Role:

Principal Investigator

Investigator Affiliation:

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

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02639

NCT ID:

NCT00101348

Start Date:

January 2005

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Carcinoma, Basal Cell
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell
  • Carcinoma, Squamous Cell
  • Carcinoma, Adenoid Cystic
  • Granuloma
  • Laryngeal Diseases
  • Lung Neoplasms
  • Pancreatic Neoplasms
  • Papilloma
  • Carcinoma, Mucoepidermoid
  • Carcinoma, Verrucous
  • Esthesioneuroblastoma, Olfactory
  • Papilloma, Inverted
  • Head and Neck Neoplasms
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Cancer Therapy and Research Center at The UT Health Science Center at San AntonioSan Antonio, Texas  78229