Reduced-intensity Therapy for Oropharyngeal Cancer in Non-smoking HPV-16 Positive Patients

NCT01663259 | Completed Results DMC

• 2 other identifiers: UMCC 2009.078HUM00032219
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Taking into account the excellent prognosis of patients with HPV-positive oropharyngeal cancer with \< 10 pack-year smoking, the investigators hypothesize that reducing the intensity of therapy for these patients will reduce treatment sequelae, notably long-term dysphagia, without affecting their cure rates. The main Aim is to assess whether reducing treatment intensity, by replacing concurrent chemotherapy with cetuximab, will indeed achieve improved long-term toxicity. The primary objectives include the following: to confirm that reducing treatment intensity in patients with HPV-related oropharyngeal cancer and \< 10 pack-year smoking history by replacing concurrent chemotherapy with concurrent cetuximab, does not significantly increase the proportion of patients whose tumors recur, compared to our previous experience in similar patients receiving chemo-RT and to compare the toxicity in patients receiving cetuximab-RT to similar patients treated with 7 weeks of chemotherapy concurrent with RT ("standard therapy") in UMCC 2-21.

Conditions

Squamous Cell Carcinoma of the Oropharynx; HPV

Outcome Measures

Primary Outcomes (1)

• Rate of Recurrence

  Number of patients whose tumors recur (includes local, regional, and distant recurrence; and second primaries). Note: Research indicates that freedom from local and regional progression (FFLRP) is a more meaningful measure. Therefore, the percentage of patients with FFLRP is included below as a Post-Hoc measure.

  2 years

Secondary Outcomes (5)

• Number of Participants With Adverse Events

  3 years

• Treatment Related Toxicities

  3 years

• Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)

  Day 7

• Mean Change in Tumor Phosphorylated EGFR (pEGFR)

  Day 7

• Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa

  Day 7

Study Arms (1)

Cetuximab

EXPERIMENTAL

Drug: Cetuximab; Radiation: Radiotherapy

Interventions

Cetuximab DRUG

Before Radiotherapy patients you will receive a single loading dose of cetuximab. Patients will also have two additional biopsies before and after cetuximab to determine how the tumor is affected. A Cetuximab infusion will also be delivered once a week during radiotherapy.Radiation will be started (70 Gy in 35 fractions over 7 weeks to the gross tumor, 50-60 Gy to subclinical target volumes) five days a week until the total dose of radiation prescribed by the doctor is reached. Radiation will be delivered concurrent with weekly cetuximab 250 mg/m2, delivered on Monday or Tuesday each week. In order to evaluate swallowing problems from radiotherapy, patients will undergo an evaluation of swallowing by videofluoroscopy (VF). Quality of Life questionnaires will be given before therapy and periodically up to 36 months after therapy. In order to assess if the tumor was completely eradicated, CT-PET scan will be performed 3 months after the completion of therapy.

Cetuximab

Radiotherapy RADIATION

Radiation will be started (70 Gy in 35 fractions over 7 weeks to the gross tumor, 50-60 Gy to subclinical target volumes) five days a week until the total dose of radiation prescribed by the doctor is reached. Radiation will be delivered concurrent with weekly cetuximab 250 mg/m2, delivered on Monday or Tuesday each week.

Cetuximab

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically-confirmed, previously untreated,stage III-IV(excluding N3 or T4) squamous cell carcinoma of the oropharynx, without evidence of distant metastasis
• Pretreatment tumor biopsy with sufficient tumor for HPV or p16 analysis is required. The tumor must be HPV(+) or p16(+)
• Smoking history \<10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing tobacco, and/or marijuana). One cannabis joint is equivalent to 5 cigarettes. (Aldington etal, Thorax 2007; 62:1058-1063). Smoking status definitions (National Health Interview Survey and Behavioral Risk Factor Surveillance System (Nelson DE etal al, Am J Pub Health 2003;93:1335):
• Smokers: smoking now every day or some days in past month
• Quitters: at least 100 cigarettes/lifetime and not smoking in the past 1-12 months
• Former smoker: at least 100 cigarettes/lifetime and not smoking \>12 months
• Never smokers: \<100 cigarettes (or equivalent)/lifetime
• KPS \> 80 (see Appendix A)
• Patients must undergo pre-treatment endoscopic tumor staging and PET-CT scanning
• Laboratory criteria:
• WBC \> 3500/ul
• granulocyte \> 1500/ul
• Platelet count \> 100,000/ul
• Total Bilirubin \< 1.5 X ULN
• AST and ALT \< 2.5 X ULN

You may not qualify if:

• Prior head and neck malignancy or history of other prior non-head and neck malignancy (excluding skin cancer and early stage treated prostate cancer) within the past 3 years
• Prior head and neck radiation or chemotherapy
• Any medical or psychiatric illness, which in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment or limit compliance with study requirements
• Patients residing in prison
• Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody or small molecule)

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

Radiation Oncology , University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Michelle Mierzwa
• Organization: University of Michigan Rogel Cancer Center

mmierzwa@umich.edu

734-936-7810

Study Officials

• Michelle Mierzwa, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: August 13, 2012
• Study Start: January 1, 2011
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: January 19, 2021
• Results First Posted: October 26, 2020

Record last verified: 2020-12

Locations

US (1)