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:

Completed

Phase:

N/A

URL:

https://clinicaltrials.gov/show/NCT01663259

Trial Eligibility

Document

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

  • ORG STUDY ID: UMCC 2009.078
  • SECONDARY ID: HUM00032219
  • NCT ID: NCT01663259
  • NCT ALIAS: NCT01649414

Conditions

  • Squamous Cell Carcinoma of the Oropharynx
  • HPV

Interventions

DrugSynonymsArms
CetuximabCetuximab

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

NameTypeDescriptionInterventions
CetuximabExperimental
  • 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)
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Recurrence
Time Frame:2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of Participants With Adverse Events
Time Frame:3 years
Safety Issue:
Description:In order to evaluate the toxicity in patients receiving cetuximab-RT, adverse events were clustered into three categories: None, Mild-Moderate (grade 1 or 2), and Severe (grade 3 or 4). Graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4).
Measure:Treatment Related Toxicities
Time Frame:3 years
Safety Issue:
Description:Toxicities are measured by number of participants who experience one or more types or indicator of toxicity, shown as all grades and grades 3-4. As each participant could have multiple toxicities, the number of incidents outnumbers the number of participants. Toxicities graded according to the CTCAE v4.
Measure:Mean Change in Tumor Epidermal Growth Factor Receptor (EGFR)
Time Frame:Day 7
Safety Issue:
Description:The ratio (fold change) of tumor EGFR post/pre loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Measure:Mean Change in Tumor Phosphorylated EGFR (pEGFR)
Time Frame:Day 7
Safety Issue:
Description:The ratio (fold change) of tumor pEGFR post/pre loading dose of cetuximab. Reported as the mean of fold changes across all participants who had an evaluable tumor sample.
Measure:Change in Tumor EGFR Level Relative to EGFR in Normal Mucosa
Time Frame:Day 7
Safety Issue:
Description:Normal mucosa EGFR was assessed for comparison with EGFR in tumor sample. The fold change in tumor EGFR level post/pre loading dose of cetuximab, relative to fold change in normal mucosa EGFR level post/pre loading dose of cetuximab was summarized across all participants who had an evaluable tumor sample and normal mucosa sample. The value reported is the ratio of fold change in tumor/fold change in buccal EGFR.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:University of Michigan Rogel Cancer Center

Last Updated

January 19, 2021