Trial Outcomes & Findings for Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Locally Advanced Head and Neck Squamous Cell Carcinoma (NCT NCT01592721)

Last Updated: 2022-09-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

6 participants

Primary outcome timeframe

1 year

Results posted on

2022-09-21

Participant Flow

Participants enrolled at two sites, University of Pittsburgh and University of Texas Health Science Center, San Antonio. Participants were followed to completion of treatment and then long-term follow up.

Subjects met eligibility for chemotherapy, radiation therapy, and anti-sense DNA injections per protocol

Participant milestones

Participant milestones
Measure	EGFR Antisense DNA 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: 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.
Treatment Period STARTED	6
Treatment Period COMPLETED	6
Treatment Period NOT COMPLETED	0
Long-term Follow-up STARTED	6
Long-term Follow-up COMPLETED	5
Long-term Follow-up NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	EGFR Antisense DNA 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: 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.
Long-term Follow-up Death	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EGFR Antisense DNA n=6 Participants 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: 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	66.5 Years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Advanced stage squamous cell carcinoma of the head and neck

Outcome measures

Outcome measures
Measure	EGFR Antisense DNA n=6 Participants 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: 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.
Toxicity Rate	20 Number of adverse events

PRIMARY outcome

Timeframe: 1 year

Population: Advanced stage squamous cell carcinoma head and neck.

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).

Outcome measures

Outcome measures
Measure	EGFR Antisense DNA n=6 Participants 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: 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.
Locoregional Progression-free Survival	6 Participants

SECONDARY outcome

Timeframe: 5 years

Population: No analysis of data was performed since there were not sufficient participants enrolled to provide meaningful results. 11 subjects would have had to complete Phase 1 in order to provide meaningful data for analysis.

Clinical secondary endpoints include objective response rates, estimated by the proportion of patients with a best response of complete response (CR), partial response (PR), or stable disease (SD) by RECIST criteria, with corresponding exact 90% confidence limits.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 years and 10 months

Population: No data analysis was performed since the study closed early due to low enrollment numbers. There was not sufficient data in order to complete the phase 1 analysis, since 11 subjects would have been required to complete.

Progression-free survival (PFS) will be measured from initial date of treatment to date of documented progression or date of death (in absence of progression) and estimated by the Kaplan-Meier method with 90% confidence limits.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

Population: Advanced stage squamous cell carcinoma head and neck

Overall survival (OS) will be measured from initial date of treatment to recorded date of death and will be estimated by the Kaplan-Meier method with 90% confidence limits.

Outcome measures

Outcome measures
Measure	EGFR Antisense DNA n=6 Participants 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: 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.
Overall Survival	5 Participants

Adverse Events

EGFR Antisense DNA

Serious events: 0 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	EGFR Antisense DNA n=6 participants at risk 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: 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.
Endocrine disorders Hyperglycemia	33.3% 2/6 • Number of events 2 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Nervous system disorders Headache	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Gastrointestinal disorders Dysguesia	50.0% 3/6 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Gastrointestinal disorders Odynphagia	100.0% 3/3 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Skin and subcutaneous tissue disorders Neck burns	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Gastrointestinal disorders Diarrhea	33.3% 2/6 • Number of events 3 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
General disorders Parotiditis	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Infections and infestations Submadibular duct infection	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
General disorders Hot Flashes/sweats	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Nervous system disorders Dizziness	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Respiratory, thoracic and mediastinal disorders Epistaxis	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Nervous system disorders Extremity tremors	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Skin and subcutaneous tissue disorders Skin burns	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Respiratory, thoracic and mediastinal disorders Dysnea on exertion	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Respiratory, thoracic and mediastinal disorders Productive cough	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Gastrointestinal disorders Decreased appetite	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Gastrointestinal disorders Dysphagia	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Nervous system disorders Peripheral neuropathy	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Blood and lymphatic system disorders Lymphopenia	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov
Renal and urinary disorders Kidney disease	16.7% 1/6 • Number of events 1 • Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 5 years Does not differ from clinical trials.gov

Additional Information

Anand B. Karnad, MD

UTexas_SanAntonio

Phone: 2104501365

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place