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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Michigan Cancer Center
Sponsor:
Information provided by (Responsible Party):
Avraham Eisbruch, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01663259
First received: July 23, 2012
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Squamous Cell Carcinoma of the Oropharynx
HPV
Radiation: Cetuximab

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced-intensity Therapy for Advanced Oropharyngeal Cancer in Non-smoking Human Papilloma Virus (HPV)-16 Positive Patients

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Rate of Recurrence [ Time Frame: Timepoints throughout 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events [ Time Frame: Timepoints throughout 3 years ] [ Designated as safety issue: Yes ]
    To compare the toxicity in patients receiving cetuximab-RT to similar patients treated with 7 weeks of chemotherapy concurrent with RT ("standard therapy")


Estimated Enrollment: 36
Study Start Date: June 2010
Estimated Study Completion Date: January 2021
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab Radiation: Cetuximab
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.

Detailed Description:

The investigators have shown in past experience a high success in getting rid of oropharyngeal cancer (tonsil or base of tongue cancer) using chemotherapy and radiation therapy in patients who have not smoked, or only smoked a minimal amount of cigarettes or equivalent. In these patients, the cancer is thought to be caused by a virus (Human Papilloma Virus, or HPV). HPV is a virus that infects the epidermis (outermost layer of skin) and mucous membranes of humans. In general, patients with HPV-related cancer such as yours have a better prognosis compared with patients whose tumors are smoking-related. Taking into account the good prognosis, it is possible that reducing the intensity of therapy will not affect the high rate of tumor control, while reducing the side-effects of therapy. In this study, the investigators plan to reduce the intensity of treatment by replacing the currently used chemotherapy drugs with an FDA approved drug, cetuximab, which is a monoclonal antibody to a growth factor which helps cancer cells grow. By opposing the effect of the growth factor, cetuximab may help radiotherapy kill cancer cells without a lot of effect on the normal tissue. It differs from chemotherapy in its more selective activity against tumors compared to normal tissue Cetuximab has the chance to preserve the high rate of success in killing the tumor but may reduce the side effects and complications of therapy in comparison to chemotherapy drugs.

The investigators would also like to know if taking cetuximab has any effect on certain cancer-related molecules in the cancer and the normal cells inside the cheek. They would like to test this by taking a small biopsy of the tumor, as well as a swab of the inside of the cheek, before and shortly after the start of therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 analysis is required. The tumor must be HPV(+)/p16(+)

Smoking history <10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing tobacco, and/or marijuana) 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

    • Creatinine clearance >30 cc/min
    • Patients must sign study specific informed consent

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663259

Contacts
Contact: Avraham Eisbruch, M.D. 734-936-4302 eisbruch@umich.edu

Locations
United States, Michigan
Radiation Oncology , University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Avraham Eisbruch, M.D.    734-936-4302    eisbruch@umich.edu   
Sponsors and Collaborators
Avraham Eisbruch
Investigators
Principal Investigator: Avraham Eisbruch, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Avraham Eisbruch, Associate Chair for Clinical Research, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01663259     History of Changes
Obsolete Identifiers: NCT01649414
Other Study ID Numbers: UMCC 2009.078, HUM00032219
Study First Received: July 23, 2012
Last Updated: June 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Oropharyngeal Neoplasms
Carcinoma, Squamous Cell
Carcinoma
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Pharyngeal Neoplasms
Stomatognathic Diseases
Cetuximab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014