Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT01592721 | Completed Phase 1 Results DMC

• 2 other identifiers: CTRC 11-47HSC20120131H
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The incorporation of novel targeted therapies to radiation therapy is of particular interest in head and neck cancer and may improve efficacy without significantly increasing toxicity. The investigators hypothesize that the addition of a second EGFR-targeted agent that inhibits EGFR at the intracellular level will improve the antitumor effect of standard radiation and cetuximab. The goal of this study is to evaluate the safety, efficacy, and the biologic effects in patients with locally advanced SCCHN of an antisense gene targeting the EGFR in combination with standard therapy with radiation and cetuximab.

Conditions

Squamous Cell Carcinoma; Head and Neck Cancer

Keywords

Carcinoma; Squamous cell carcinoma; Head and neck neoplasms; Cetuximab

Outcome Measures

Primary Outcomes (2)

• Toxicity Rate

  This is a 2-stage clinical trial. In the first stage, toxicity will be the primary endpoint. Toxicity measures will be graded according to NCI CTCAE version 4.0. All AEs reported are grade 1 to grade 3 AEs.

  1 year

• Locoregional Progression-free Survival

  In the second stage (phase II component), the primary endpoint will be locoregional progression-free survival (PFS) at 1 year measured from patient initial date of treatment to date of documented progression or date of death (in absence of progression).

  1 year

Secondary Outcomes (3)

• Tumor Response

  5 years

• Progression-free Survival

  8 years and 10 months

• Overall Survival

  5 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. Patients will receive a total of up to 4 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation. Patients will receive standard radiation 70 Gy/200 cGy/daily, 5 days/week, with concurrent cetuximab 250 mg/m2, after a loading dose of 400 mg/m2 2 weeks prior to starting radiation.

Biological: EGFR Antisense DNA

Interventions

EGFR Antisense DNA BIOLOGICAL

EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. Patients will receive a total of up to 4 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation. Patients will receive standard radiation 70 Gy/200 cGy/daily, 5 days/week, with concurrent cetuximab 250 mg/m2, after a loading dose of 400 mg/m2 2 weeks prior to starting radiation.

EGFR Antisense DNA

Eligibility Criteria

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

You may qualify if:

• First stage Patients with AJCC 7th edition stage IVA-IVC or recurrent or metastatic head and neck cancer will be eligible. Patients with M1 disease must have asymptomatic or low volume distant metastasis and require palliation for local and regional disease.
• Second stage (phase II part) Patients with AJCC 7th edition stage III-IVB (T1-T4, N1-3M0) head and neck cancer, except WHO type II and III nasopharyngeal cancer, including unknown primary tumors.
• Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or variants or poorly differentiated carcinoma.
• Unidimensionally measurable disease (RECIST criteria).
• ECOG performance status of 0-2
• In the second stage of the study, therapy will be administered with a curative intent and patients should not have recurrent disease or distant metastasis.
• Primary tumor and/or lymphadenopathy should be technically suitable for intratumoral injections. The Otolaryngologist specialist on the head and neck team will determine this feasibility.
• Participating patients should agree to undergo a tumor biopsy at baseline as well as approximately 2 weeks later as specified in study schema.
• Prior treatment
• First stage: any prior treatment, except prior therapy, which specifically and directly targets the EGFR pathway, administered within the last 6 months. No prior radiation therapy to the head and neck.
• Second stage: no prior chemotherapy, biologic/molecular targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer.
• Prior surgical therapy will consist only of incisional or excisional biopsy, including tonsillectomy, and organ sparing procedures, including neck dissection. Any non-biopsy surgical procedure for head and neck cancer must have taken place at least one month before initiating protocol treatment, at the treating physician's discretion.
• Patients must have organ and marrow function as defined below:
• Absolute neutrophil count above/equal to 1,000/µL Platelets above/equal to 75,000/µL Hemoglobin above/ equal to 10 g/dL Total bilirubin \<2 x upper normal institutional limits Creatinine clearance \> 20 mL/min
• Age 18 years or older

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 M1 disease will be excluded.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• University of Pittsburgh: collaborator

Study Sites (2)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Cancer Therapy and Research Center at UTHSCSA

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Anand B. Karnad, MD
• Organization: UTexas_SanAntonio

regulatoryaffairs@uthscsa.edu

2104501365

Study Officials

• Anand Karnad, MD

  University of Texas Health Science Center San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: April 26, 2012
• First Posted: May 7, 2012
• Study Start: April 1, 2013
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: September 21, 2022
• Results First Posted: September 21, 2022

Record last verified: 2022-08

Locations

US (2)