Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Cetuximab

Immunoglobulins

Interleukin-12

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Adjuvants, Immunologic

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive cetuximab IV over 1-2 hours on day 1 and recombinant interleukin-12 SC on days 2 and 5 beginning in course 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving clinical response or stable disease may continue with therapy until disease progression.

Edodekin alfa

Laboratory Biomarker Analysis

William E Carson

This phase I/II trial studies the side effects and best dose of recombinant interleukin-12 when given together with cetuximab and to see how well they work in treating patients with squamous cell carcinoma of the head and neck that has come back, spread to another place in the body, or cannot be removed by surgery. Recombinant interleukin-12 may stimulate the white blood cells to kill tumor cells. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread Giving recombinant interleukin-12 together with cetuximab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To find a safe and tolerable interleukin (IL)-12 (recombinant interleukin-12) dose for use in combination with cetuximab in patients with squamous cell carcinoma of the head and neck. (Phase I) II. To determine the response rate to the combination of IL-12 and cetuximab. (Phase II)

SECONDARY OBJECTIVES:

I. To characterize the immunologic effects of IL-12 when administered in combination with cetuximab.

OUTLINE: This is a phase I, dose-escalation study of recombinant IL-12 followed by a phase II study.

Patients receive cetuximab intravenously (IV) over 1-2 hours on day 1 and recombinant interleukin-12 subcutaneously (SC) on days 2 and 5 beginning in course 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving clinical response or stable disease may continue with therapy until disease progression.

After completion of study treatment, patients are followed up for 1 year.

Cetuximab and Recombinant Interleukin-12 in Treating Patients With Squamous Cell Carcinoma of the Head and Neck That is Recurrent, Metastatic, or Cannot Be Removed by Surgery

A Phase I/II Trial of Cetuximab in Combination With Interleukin-12 Administered to Patients With Unresectable Primary or Recurrent Squamous Cell Carcinoma of the Head and Neck

The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Explores graphically how changes in this marker differ between those with versus without an objective response to therapy as well as other potential factors.

Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

The Kaplan-Meier method will be used to estimate overall survival distribution.

The Kaplan-Meier method will be used to estimate time to progression distributions.

National Cancer Institute (NCI)

Toxicities were graded using the National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.

Arm 1 (Phase I)

Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.

Arm II (Phase II)

Arm 1 (Phase 1)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

William Carson, MD

Number of Dose-limiting Toxicity Incidents to Determine the Maximum Tolerated Dose of IL-12, Evaluated Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

Proportion of Patients Who Have Any Response to Treatment (Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors (Phase II)

Unable to compare the plasma levels of interferon-gamma between those with versus without an objective response to therapy due to no objective response seen for Phase I or Phase II patients.

Induction of Systemic Plasma Levels of Interferon-gamma

Number of Confirmed Clinical Responses (Phase I)

Overall Survival (Phase II)

Proportion of Patients Who Are Progression-free (Phase I)

Time to Disease Progression (Phase II)

Overall Study

Pembrolizumab

Immune Checkpoint Inhibitors

Patients receive recombinant interleukin-12 SC on days 2, 5, 9, and 12 and pembrolizumab IV over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, PET, and MRI, as well as collection of blood during screening, on study, and during follow-up. Patients also undergo a tumor biopsy during screening and on study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Diwakar Davar

This phase I trial studies the side effects and best dose of pembrolizumab and recombinant interleukin-12 in treating patients with solid tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Recombinant interleukin-12 may kill tumor cells by blocking blood flow to the tumor and by stimulating white blood cells to kill tumor cells. Giving pembrolizumab and recombinant interleukin-12 may work better than giving pembrolizumab alone in treating patients with solid tumors.

PRIMARY OBJECTIVE:

I. Establish the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of edodekin alfa (recombinant human interleukin \[rhIL\]-12) in combination with pembrolizumab (MK-3475).

SECONDARY OBJECTIVES:

I. Evaluate the safety of the regimen by continuously monitoring adverse events that will be documented utilizing Common Terminology Criteria for Adverse Events (CTCAE) version (v).5.0.

II. Evaluate the overall response rate (Response Evaluation Criteria in Solid Tumors \[RECIST\] v.1.1) and the progression free survival of patients enrolled on the study.

III. Measure CD8+ T cell infiltration by immunohistochemistry in tumor biopsies obtained pre-treatment, after one week of rhIL-12 and after 2 cycles of pembrolizumab (MK-3475) in combination with rhIL-12.

EXPLORATORY OBJECTIVE:

I. Conduct exploratory translational laboratory correlative studies utilizing banked biospecimens (tumor, blood, and stool) obtained pre-treatment and during therapy.

OUTLINE: This is a dose-escalation study of recombinant interleukin-12.

Patients receive recombinant interleukin-12 subcutaneously (SC) on days 2, 5, 9, and 12 and pembrolizumab intravenously (IV) over 30 minutes on day 8 of cycle 1 and day 1 of subsequent cycles. Treatment continues for 28 days for cycle 1 and repeats every 21 days for subsequent cycles for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patient then receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 additional cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT), positron emission tomography (PET), and/or magnetic resonance imaging (MRI), as well as collection of blood during screening, on study, and during follow-up. Patients also undergo a tumor biopsy during screening and on study.

After completion of study treatment, patients are followed up every 12 weeks for 2 year and then every 24 weeks for up to 5 years.

Pembrolizumab and Recombinant Interleukin-12 in Treating Patients With Solid Tumors

A Phase 1 Study of Pembrolizumab (MK-3475) in Combination With Recombinant Interleukin-12 in Patients With Solid Tumors

Will conduct exploratory translational laboratory correlative studies utilizing banked biospecimens (tumor, blood and stool) obtained at baseline and during therapy.

Adverse events will be tabulated by Common Terminology Criteria for Adverse Events (CTCAE) grade, CTCAE category, relatedness to treatment and dose level.

The product-limit (Kaplan-Meier) progression-free survival function, with a 95% confidence region, will be determined for all patients and for patients treated at the MTD.

Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. The proportion of patients experiencing confirmed overall (complete or partial) response will be calculated, as will a 95% exact (Klopper-Pearson) binomial confidence interval for all patients, and patients treated at the MTD (a confirmed clinical tumor response is defined to be either a complete response or partial response noted as the objective status on 2 consecutive evaluations at least \>= 4 weeks apart.).

Will be assessed by immunohistochemistry. Will be compared to pre-treatment biopsy specimens by the Wilcoxon signed-rank test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cetuximab and Recombinant Interleukin-12 in Treating Patients With Squamous Cell Carcinoma of the Head and Neck That is Recurrent, Metastatic, or Cannot Be Removed by Surgery	NCT01468896	Metastatic Head... Recurrent Head ... Unresectable He...	Cetuximab Edodekin alfa Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Pembrolizumab and Recombinant Interleukin-12 in Treating Patients With Solid Tumors	NCT03030378	Metastatic Mali... Unresectable Ma...	Biopsy Biospecimen Col... Computed Tomogr... Edodekin alfa Magnetic Resona... Pembrolizumab Positron Emissi...	18 Years -	National Cancer Institute (NCI)
Cetuximab and Recombinant Interleukin-12 in Treating Patients With Squamous Cell Carcinoma of the Head and Neck That is Recurrent, Metastatic, or Cannot Be Removed by Surgery	NCT01468896	Metastatic Head... Recurrent Head ... Unresectable He...	Cetuximab Edodekin alfa Laboratory Biom...	18 Years -	National Cancer Institute (NCI)

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