Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01254617
First received: December 3, 2010
Last updated: March 19, 2014
Last verified: March 2014
  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).


Enrollment: 17
Study Start Date: February 2011
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (lenalidomide and cetuximab)
Patients receive lenalidomide PO QD 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:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: laboratory biomarker analysis
Correlative studies

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 V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal and head/neck cancers as monitored by measurable disease by Response Evaluation Criteria In Solid Tumors (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 lenalidomide orally (PO) once daily (QD) on days 1-21 and cetuximab intravenously (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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky > 60%)
  • Life expectancy > 3 months
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count (ANC) > 1,500/mcL
  • Platelet count > 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal (ULN)
  • Creatinine clearance > 60 mL/min/1.73m^2 as calculated using modified Cockcroft-Gault formula
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide. Further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
  • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Able to take aspirin (81 or 325 mg) daily for prophylactic anticoagulation

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (>= grade 3) due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Uncontrolled brain metastases; patients who have received definitive therapy, including radiation, and are not requiring ongoing medical therapy (i.e. steroids) for brain metastases will be allowed
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or cetuximab or other agents used in study
  • Patients with a recent history of deep vein thrombosis (DVT)/pulmonary embolism (PE) requiring therapy (within 3 months)
  • Patients with history of toxicity >= grade 3 with prior epidermal growth factor receptor (EGFR) directed therapy
  • Patient with confirmed history of interstitial lung disease
  • Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because lenalidomide is Food and Drug Administration (FDA) pregnancy category X agent with the potential for teratogenic or abortifacient effects; cetuximab is FDA pregnancy category C; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide or cetuximab, breastfeeding should be discontinued if the mother is treated with either agent; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01254617

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Erin Bertino Ohio State University
  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, NCI-2011-02557, CDR0000690277, OSU-10112, 10112, 8695, U01CA076576, P30CA016058
Study First Received: December 3, 2010
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on April 15, 2014