Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer
This study is currently recruiting participants.
Verified February 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01254617
First received: December 3, 2010
Last updated: February 5, 2013
Last verified: February 2013
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Purpose
This phase I clinical trial is studying the side effects and the best dose of lenalidomide when given together with cetuximab in treating patients with advanced colorectal cancer or head and neck cancer. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as cetuximab, 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 cancer-killing substances to them. Giving lenalidomide together with cetuximab may kill more tumor cells
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma Recurrent Colon Cancer Recurrent Metastatic Squamous Neck Cancer With Occult Primary Recurrent Rectal 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 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 Stage IVA Colon Cancer Stage IVA Rectal Cancer Stage IVB Colon Cancer Stage IVB Rectal Cancer Tongue Cancer |
Biological: cetuximab Drug: lenalidomide Other: laboratory biomarker analysis |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Enhancement of Cetuximab-Induced Antibody-Dependent Cellular Cytotoxicity (ADCC) With Lenalidomide in Advanced Solid Tumors: a Phase I/IB Study |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Maximum-tolerated dose of lenalidomide in combination with cetuximab, determined by dose-limiting toxicity graded by the NCI CTCAE version 4 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns in each of the treatment arms.
Secondary Outcome Measures:
- Response as measured by RECIST [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]The statistical analysis corresponding to the evaluation of patient responses in measurable disease will be descriptive in nature. The reporting of the patient responses will include a description of all patients enrolled on study as well as evaluable patients receiving at least one cycle of combination therapy with lenalidomide. The response rate analysis will include an explanation of which patients were excluded.
- Antibody-dependent cytotoxic activity [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]A bivariate plot will be used to describe the relationship between tumor shrinkage and peak ADCC and cytokine levels over time. Results will be summarized using descriptive statistics (i.e. means, medians, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data).
- Natural killer cell cytokine production [ Time Frame: Up to 6 weeks ] [ Designated as safety issue: No ]A bivariate plot will be used to describe the relationship between tumor shrinkage and peak ADCC and cytokine levels over time. Results will be summarized using descriptive statistics (i.e. means, medians, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data).
| Estimated Enrollment: | 24 |
| Study Start Date: | February 2011 |
| Estimated Primary Completion Date: | February 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (lenalidomide and cetuximab)
Patients receive oral lenalidomide once daily on days 1-21 and cetuximab IV over 1-2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Biological: cetuximab
Given IV
Other Names:
Drug: lenalidomide
Given orally
Other Names:
Other: laboratory biomarker analysis
Correlative studies
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Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose of lenalidomide when given in combination with cetuximab in patients with advanced colorectal or squamous cell head and neck cancer.
SECONDARY OBJECTIVES:
I. To evaluate response in refractory KRAS wild-type colorectal and head/neck cancers as monitored by measurable disease by RECIST criteria.
II. To measure antibody-dependent cytotoxic activity (ADCC) in patients receiving lenalidomide plus cetuximab.
III. To measure natural killer cell cytokine production in patients receiving lenalidomide plus cetuximab.
IV. To describe fragment c gamma receptor polymorphisms.(Exploratory) V. To describe baseline immune cell function. (Exploratory)
OUTLINE: This is a dose-escalation study of lenalidomide in patients with head and neck cancer or colorectal cancer followed by an expansion-cohort study in patients with colorectal cancer.
Patients receive oral lenalidomide once daily on days 1-21 and cetuximab IV over 1-2 hours on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up for 6 weeks.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor meeting 1 of the following criteria:
- KRAS wild-type colorectal cancer
- Squamous cell head and neck cancer
- Metastatic or unresectable disease for which standard curative or palliative measures do not exist or are no longer effective
Patients with colorectal cancer must be resistant or refractory to cetuximab or panitumumab (expansion cohort)
- Progressive disease during cetuximab or panitumumab therapy or within 3 months after cetuximab or panitumumab therapy
No uncontrolled brain metastases
- Patients who have received definitive therapy, including radiotherapy, and are not requiring ongoing medical therapy (i.e., steroids) for brain metastases allowed
- ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
- Life expectancy > 3 months
- WBC > 3,000/mm³
- ANC > 1,500/mm³
- Platelet count > 100,000/mm³
- Total bilirubin normal
- AST and ALT < 2.5 times upper limit of normal (ULN)
- Creatinine clearance > 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must abstain from heterosexual intercourse or use 2 acceptable methods of contraception (1 highly effective method and 1 additional method at the same time) ≥ 28 days prior to, during, and ≥ 28 days after completion of lenalidomide therapy
- Able to take aspirin (81 or 325 mg) daily for prophylactic anticoagulation
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide, cetuximab, or other agents used in study
- No DVT/PE requiring therapy within the past 3 months
- No history of toxicity ≥ grade 3 with prior EGFR-directed therapy
- No history of interstitial lung disease.
No uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness and/or social situations that would limit compliance with study requirements
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Any number of prior therapies allowed
- Prior epidermal growth factor receptor (EGFR)-directed therapy (tyrosine kinase inhibitors and monoclonal antibodies - including cetuximab, panitumumab, or investigational EGFR-directed monoclonal antibodies) allowed (for patients in phase I dose escalation)
- At least 28 days since prior monoclonal antibody
- More than 28 days since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered from ≥ grade 3 adverse events
Must take concurrent aspirin daily
- Patients intolerant to aspirin may use warfarin or low-molecular weight heparin
- No other concurrent investigational agents
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01254617
Locations
| United States, Ohio | |
| Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | Recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Erin M. Bertino 614-293-8858 erin.bertino@osumc.edu | |
| Principal Investigator: Erin M. Bertino | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Erin Bertino | Ohio State University Comprehensive Cancer Center |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01254617 History of Changes |
| Other Study ID Numbers: | NCI-2011-02557, 10112, U01CA076576 |
| Study First Received: | December 3, 2010 |
| Last Updated: | February 5, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Nose Neoplasms Carcinoma Colonic Neoplasms Rectal Neoplasms Carcinoma, Squamous Cell Head and Neck Neoplasms Laryngeal Diseases Tongue Neoplasms Carcinoma, Verrucous Neoplasms, Unknown Primary Hypopharyngeal Neoplasms Laryngeal Neoplasms Paranasal Sinus Neoplasms Oropharyngeal Neoplasms Nasopharyngeal Neoplasms |
Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Neoplasms, Squamous Cell Respiratory Tract Diseases |
ClinicalTrials.gov processed this record on May 23, 2013