Safety and Efficacy of Radiation/Cetuximab Plus EGFR Antisense DNA for Head and Neck Squamous Cell Carcinoma

NCT00903461 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 06-1211R21CA130241-01A1
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The Epidermal Growth Factor Receptor (EGFR) is highly expressed in SCCHN and its overexpression is associated with poor patient outcome. EGFR is a promising target of anticancer therapy. We have developed EGFR antisense DNA as a safe and potentially efficacious treatment for SCCHN as shown in a previous phase I study conducted at the University of Pittsburgh. Cetuximab (Erbitux or C225) is a chimerized EGFR monoclonal antibody that has produced positive results in a phase III trial in SCCHN when added to radiation therapy and was approved by the FDA for the treatment of locally advanced SCCHN. Radiation plus cetuximab is considered a standard treatment, especially for patients who are not good candidates for chemotherapy. In the current study, we plan to evaluate the addition of intratumoral EGFR antisense DNA (EGFR AS) to standard radiation with concurrent cetuximab in patients.

Conditions

Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head And Neck

Outcome Measures

Primary Outcomes (1)

• Disease progression

  Change in tumor size based on CT or MRI scans of the same tumor(s) of the head and/or neck as compared to baseline measurement.

  baseline, 4, 7, 10, and 13 months after study treatment.

Secondary Outcomes (4)

• Number of adverse events associated with study treatment

  2 weeks

• Response rate

  baseline, 4, 7, 10, and 13 months after study treatment.

• Determine the effect of EGFR antisense therapy on EGFR and EGFR-related biomarkers.

  3 years

• Examine the transfection of the EGFR antisense gene therapy in vivo.

  3 Years

Study Arms (1)

EGFR Antisense DNA

EXPERIMENTAL

EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. Subjects will receive a total of up to 7 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation. Patients will receive a total EGFR AS dose of 1.92 milligrams in 1.78 milliliters on each weekly treatment. This dose may be delivered equally in the same tumor site per weekly session, the primary tumor or cervical lymph nodes.

Biological: EGFR Antisense DNA

Interventions

EGFR Antisense DNA BIOLOGICAL

* Intratumoral EGFR AS injections weekly x 7 weeks (or less if there is no identifiable tumor), starting 2 weeks prior to radiation. The first EGFR AS injection must be given after cetuximab is administered. Subsequent EGFR AS injections can be given before or after cetuximab is administered. Injections will be in the primary and/or lymph nodes. One site will be injected per weekly session. If it is necessary the antisense injection can be scheduled within 1 business day of the original schedule date and then resume the original schedule * EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. The same lesion (primary tumor or lymph node) will be injected during treatment.

EGFR Antisense DNA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Severe renal insufficiency (creatinine clearance \< 20 mL/min)
• Treatment with anticoagulants, except when used to maintain the patency of a central venous line, or INR \>1.5, or PTT ratio \>1.5.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure.
• Patients may not be receiving any other investigational agents.
• No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, DCIS or LCIS of the breast, localized early stage prostate cancer, or malignancy that has been treated with a curative intent with a 3-year disease-free survival.
• Pregnant women are excluded from this study because cetuximab, EGFR AS, and radiation have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab and EGFR AS, breastfeeding should be discontinued if the mother is treated with cetuximab. The effects of cetuximab and EGFR AS on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with cetuximab. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. . HIV status of the patient will be obtained from the patient's history via discussion with the investigator. HIV testing is not required.
• Prior severe infusion reaction to a monoclonal antibody.
• Patients who are not informed of and are not willing to comply with the investigational nature of the study and have not signed a written informed consent in accordance with institutional and good clinical practice guidelines.
• Phase 2 ONLY (second stage) - Subjects with M1 disease will be excluded.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Julie Bauman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2009
• First Posted: May 18, 2009
• Study Start: April 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: August 1, 2016
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (1)