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

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: September 23, 2014
Last verified: August 2014

December 3, 2010
September 23, 2014
February 2011
January 2014   (final data collection date for primary outcome measure)
Maximum-tolerated dose of lenalidomide with cetuximab, defined as the highest dose level at which 0 or 1 patients out of 6 experiences a dose limiting toxicity graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Toxicity will be classified as either possibly, probably, or definitely related to study treatment. 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.
  • Maximum-tolerated dose of lenalidomide in combination with cetuximab [ Designated as safety issue: Yes ]
  • Adverse events as assessed by NCI CTCAE v.4 [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01254617 on ClinicalTrials.gov Archive Site
  • Response as measured by RECIST [ Time Frame: Up to 6 weeks after completion of study treatment ] [ 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.
  • ADCC activity [ Time Frame: Up to week 5 ] [ 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 activation [ Time Frame: Up to week 5 ] [ 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).
  • Response as measured by RECIST [ Designated as safety issue: No ]
  • Antibody-dependent cytotoxic activity [ Designated as safety issue: No ]
  • Natural killer cell cytokine production [ Designated as safety issue: No ]
  • Fragment c gamma receptor polymorphism status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Immune cell activation [ Time Frame: Baseline ] [ Designated as safety issue: No ]
Not Provided
 
Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer
Enhancement of Cetuximab-Induced Antibody-Dependent Cellular Cytotoxicity (ADCC) With Lenalidomide in Advanced Solid Tumors: A Phase I/IB Study

This phase I trial studies the side effects and the best dose of lenalidomide when given together with cetuximab in treating patients with colorectal cancer or head and neck cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. Giving lenalidomide together with cetuximab may be a better treatment for colorectal cancer or head and neck cancer.

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.

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 treatment, patients are followed up for 6 weeks.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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 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
  • Salivary Gland Squamous Cell Carcinoma
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IVA Colon Cancer
  • Stage IVA Rectal Cancer
  • Stage IVA Salivary Gland Cancer
  • Stage IVA Squamous Cell Carcinoma of the Larynx
  • Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • Stage IVB Colon Cancer
  • Stage IVB Rectal Cancer
  • Stage IVB Salivary Gland Cancer
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • Stage IVC Salivary Gland Cancer
  • Stage IVC Squamous Cell Carcinoma of the Larynx
  • Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVC Squamous Cell Carcinoma of the Oropharynx
  • Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Verrucous Carcinoma of the Larynx
  • Stage IVC Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Untreated Metastatic Squamous Neck Cancer With Occult Primary
  • 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
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.
Interventions:
  • Biological: cetuximab
  • Drug: lenalidomide
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
22
Not Provided
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; eligible malignancies include: colorectal cancer KRAS wild-type and squamous cell head and neck cancer
  • No curative intent therapy available; there is no limit on prior number of therapies; prior epidermal growth factor receptor (EGFR)-directed therapy (tyrosine kinase inhibitors and monoclonal antibodies - including cetuximab, panitumumab, or investigational EGFR directed monoclonal antibodies) will be allowed in the phase I dose escalation; patients who have received monoclonal antibody therapy must be off all monoclonal antibodies four weeks (28 days) prior to study treatment; no chemotherapy within 28 days of trial medication
  • There will be an expansion cohort for colorectal cancer patients only; for the expansion cohort, there is no limit on prior chemotherapy; the colorectal expansion cohort will include patients with cetuximab or panitumumab-resistant or refractory disease (progression during cetuximab/panitumumab therapy or within 3 months of cetuximab/panitumumab therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky > 60%)
  • Life expectancy of greater than 3 months
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
  • Creatinine clearance > 60 mL/min/1.73 m^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 (patients intolerant to aspirin may use warfarin or low molecular weight heparin)

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 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; breastfeeding should be discontinued if the mother is treated with either agent
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01254617
NCI-2011-02557, NCI-2011-02557, CDR0000690277, OSU-10112, 10112, 8695, P30CA016058, UM1CA186712, U01CA076576
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Erin Bertino Ohio State University
National Cancer Institute (NCI)
August 2014

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