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: July 11, 2014
Last verified: March 2014

December 3, 2010
July 11, 2014
February 2011
January 2014   (final data collection date for primary outcome measure)
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.
  • 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 ] [ 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).
  • 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 ]
Not Provided
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 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.

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.

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 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
    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:

  • 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
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, U01CA076576, P30CA016058
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Erin Bertino Ohio State University
National Cancer Institute (NCI)
March 2014

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