Clinical Trials /

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

NCT01663259

Description:

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

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

Title

  • Brief Title: Reduced-intensity Therapy for Oropharyngeal Cancer in Non-smoking HPV-16 Positive Patients
  • Official Title: Reduced-intensity Therapy for Advanced Oropharyngeal Cancer in Non-smoking Human Papilloma Virus (HPV)-16 Positive Patients
  • Clinical Trial IDs

    NCT ID: NCT01663259

    NCT Alias ID: NCT01649414

    ORG ID: UMCC 2009.078

    NCI ID: HUM00032219

    Trial Conditions

    Squamous Cell Carcinoma of the Oropharynx

    HPV

    Trial Interventions

    Drug Synonyms Arms
    Cetuximab Cetuximab

    Trial 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.

    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.

    Trial Arms

    Name Type Description Interventions
    Cetuximab Experimental Cetuximab

    Eligibility 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 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

    - Creatinine clearance >30 cc/min

    - Patients must sign study specific informed consent

    - Patients must have, in the opinion of a treating physician, tumor that is
    accessible to biopsy in the clinic.

    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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Rate of Recurrence

    Secondary Outcome Measures

    Number of Participants with Adverse Events

    Trial Keywords