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
  Purpose

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.


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 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
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 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.


Secondary Outcome Measures:
  • 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).


Other Outcome Measures:
  • 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 ]

Enrollment: 22
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, P30CA016058, UM1CA186712, U01CA076576
Study First Received: December 3, 2010
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Verrucous
Colonic Neoplasms
Head and Neck Neoplasms
Laryngeal Diseases
Laryngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Unknown Primary
Oropharyngeal Neoplasms
Paranasal Sinus Neoplasms
Rectal Neoplasms
Salivary Gland Neoplasms
Colonic Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Mouth Diseases
Mouth Neoplasms
Nasopharyngeal Diseases
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on October 22, 2014