Clinical Trials /

De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

NCT02281955

Description:

The purpose of this research study is to learn about the effectiveness of using lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck. The cure rate for this type of cancer is estimated to be high, > 90%. The standard treatment for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is performed afterwards. This standard regimen causes a lot of side effects and long term complications. This study is evaluating whether a lower dose of radiation and chemotherapy may provide a similar cure rate as the longer, more intensive standard regimen. Patients in this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

De-intensification of <span class="go-doc-concept go-doc-intervention">Radiation</span> and <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

Title

  • Brief Title: De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study
  • Official Title: De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal Squamous Cell Carcinoma
  • Clinical Trial IDs

    NCT ID: NCT02281955

    ORG ID: LCCC1413

    Trial Conditions

    Carcinoma, Squamous Cell

    Head and Neck Neoplasms

    Oropharyngeal Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    Cisplatin (or alternative) De-escalated Radiation and Chemotherapy

    Trial Purpose

    The purpose of this research study is to learn about the effectiveness of using
    lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated
    low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck.
    The cure rate for this type of cancer is estimated to be high, > 90%. The standard treatment
    for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is
    performed afterwards. This standard regimen causes a lot of side effects and long term
    complications. This study is evaluating whether a lower dose of radiation and chemotherapy
    may provide a similar cure rate as the longer, more intensive standard regimen. Patients in
    this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy.

    Detailed Description

    The proposed study is a follow-up study to NCT01530997. In NCT01530997, patients with HPV
    positive and/or p16 positive low-risk oropharyngeal squamous cell carcinoma (OPSCC) received
    de-intensified chemoradiotherapy (CRT) followed by a limited surgical evaluation. The
    primary endpoint of NCT01530997 was the rate of pathological complete response (pCR) after
    CRT. Power computations were performed for N=40 and were based on the null hypothesis (H0)
    that the pCR for de-intensified chemoradiotherapy is at least 87%, the historical rate. The
    type 1 error for this calculation was 14.2%. 43 patients enrolled and 38 were evaluable for
    the primary endpoint. The observed pCR rate was 89% (34/38). Since the observed pCR rate was
    excellent in NCT01530997 and was in concordance with the expected rate, in the proposed
    study we will not mandate a post-CRT surgical evaluation. Instead a PET/CT 10 to 16 weeks
    post-CRT will be used to determine whether a surgical evaluation is needed.

    Trial Arms

    Name Type Description Interventions
    De-escalated Radiation and Chemotherapy Experimental Patients will receive Intensity Modulated Radiotherapy Treatments (IMRT), 60 Gy at 2 Gy/fx. The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses. Chemotherapy will not be given to patients with T0-2 N0-1 disease, 10 pack years smoking history. Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed. Cisplatin (or alternative)

    Eligibility Criteria

    Inclusion Criteria:

    1. 18 years of age (no upper age limit)

    2. T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx

    3. Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive

    4. 10 pack-years smoking history or 30 pack-years smoking history WITH 5 years
    abstinence from smoking

    5. Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks
    prior to registration

    6. ECOG Performance Status 0-1

    7. CBC/differential obtained within 8 weeks prior to registration, with adequate bone
    marrow function defined as follows: Platelets 100,000 cells/mm3; Hemoglobin 8.0
    g/dl.

    8. Adequate renal and hepatic function within 4 weeks prior to registration, defined as
    follows: Serum creatinine < 2.0 mg/dl; Total bilirubin < 2 x the institutional ULN;
    AST or ALT < 3 x the institutional ULN.

    9. Negative serum pregnancy test within 2 weeks prior to registration for women of
    childbearing potential

    10. Women of childbearing potential and male participants who are sexually active must
    practice adequate contraception during treatment and for 6 weeks following treatment.

    11. Patients must be deemed able to comply with the treatment plan and follow-up
    schedule.

    12. Patients must provide study specific informed consent prior to study entry

    Exclusion Criteria:

    1. Prior history of radiation therapy to the head and neck

    2. Prior history of head and neck cancer.

    3. Unresectable disease (e.g. immobile node on physical exam, nodal disease that
    radiographgically involves the carotid arteries, nerves)

    4. Extensive history of using smokeless tobacco products or marijuana defined as daily
    use >/= 5 years.

    5. Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive
    heart failure requiring hospitalization within the last 6 months; Transmural
    myocardial infarction within the last 6 months; Acute bacterial or fungal infection
    requiring intravenous antibiotics at the time of registration; Chronic Obstructive
    Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization
    or precluding study therapy at the time of registration; Hepatic insufficiency
    resulting in clinical jaundice and/or coagulation defects (Note, however, coagulation
    parameters are not required for entry into this protocol); Pre-existing grade 2
    neuropathy; Prior organ transplant.

    6. Known HIV positive.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    2 year Progression Free Survival after de-intensified CRT in HPV-positive and/or p16 positive low-risk OPSCC

    Secondary Outcome Measures

    Local control rate

    Regional control rate

    Local-regional control rate

    Distant metastasis free survival

    Overall survival rate

    Head and neck quality of life assessments

    Speech and swallowing function

    Trial Keywords

    Human Papillomavirus

    Oropharynx

    Oropharyngeal Squamous Cell Carcinoma

    Squamous Cell Carcinoma

    Radiation Therapy

    Chemotherapy

    p16