Phase 2
Completed N=6
Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Locally Advanced Head and Neck Squamous Cell Carcinoma
Source: ClinicalTrials.gov NCT01592721 ↗Enrolled (actual)
6
Serious AEs
0.0%
Results posted
Sep 2022
Primary outcomePrimary: Toxicity Rate — 20 Number of adverse events
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Toxicity Rate |
20 | — |
| PRIMARY Locoregional Progression-free Survival |
6 | — |
| SECONDARY Tumor Response |
— | — |
| SECONDARY Progression-free Survival |
— | — |
| SECONDARY Overall Survival |
5 | — |
Eligibility Criteria
Inclusion Criteria
- 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 20 mL/min
- Age 18 years or older
- Because radiation therapy is known to be teratogenic and EFGR inhibitors may have teratogenic potential, women of childbearing 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, and for 3 months after completing study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- Severe renal insufficiency (creatinine clearance 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, breastfee
Data sourced from ClinicalTrials.gov (NCT01592721). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.