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Enhancement of Cetuximab-Induced Antibody-Dependent Cellular Cytotoxicity (ADCC) With Lenalidomide in Advanced Solid Tumors: a Phase I/IB Study


Phase 1
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

Enhancement of Cetuximab-Induced Antibody-Dependent Cellular Cytotoxicity (ADCC) With Lenalidomide in Advanced Solid Tumors: a Phase I/IB Study


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.


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 glutamci 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 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose of lenalidomide in combination with cetuximab, determined by dose-limiting toxicity graded by the NCI CTCAE version 4

Outcome Description:

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.

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Erin Bertino

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02557

NCT ID:

NCT01254617

Start Date:

February 2011

Completion Date:

Related Keywords:

  • 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
  • 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

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210