Study of Chemotherapy Prior to Radiotherapy and Chemotherapy in Patients With HPV Associated Cancer of the Oral Cavity

This study has been terminated.
(Principal Investigator left institution. IRB approval lapsed.)
Sponsor:
Information provided by (Responsible Party):
North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:
NCT01525927
First received: February 1, 2012
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

This study looks at the use of three cycles of chemotherapy given prior to radiation therapy in patients with cancer of the oral cavity and evidence of prior exposure to Human Papilloma Virus (HPV). Patients with cancer of the oral cavity who have evidence of exposure to HPV have a better prognosis than those who do not have such evidence of exposure to HPV. The main hypothesis of this study is that using three cycles of chemotherapy prior to embarking on radiation therapy will allow the use of reduced doses of radiation therapy and, therefore, less radiation induced side-effects. The primary objective is to determine the activity of this pre-radiation chemotherapy strategy along with reduced dose levels of radiation with or without chemotherapy during the radiation phase. The effectiveness of the strategy will be assessed at three months following the completion of the radiation therapy phase and also at two years following completion of the radiation therapy.


Condition Intervention Phase
Oropharyngeal Neoplasms
Drug: chemotherapy
Radiation: radiotherapy
Radiation: Reduced dose radiotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Neoadjuvant Chemotherapy for HPV-Associated Squamous Cell Carcinoma of the Oropharynx Followed by Reduced Dose Radiotherapy/Chemoradiotherapy for Responders or Standard Dose Chemoradiotherapy for Non-Responders

Resource links provided by NLM:


Further study details as provided by North Shore Long Island Jewish Health System:

Primary Outcome Measures:
  • Response (CR+PR) status at 3 months post-therapy [ Time Frame: 3 months following completion of radiation phase ] [ Designated as safety issue: No ]
    The 3-month response rate will be estimated using standard methods for estimating proportions and their 95% one-sided confidence intervals (CIs). Comparison to the historical control data will be carried out using a chi-square test for comparing proportions (or a Fisher exact test if an expected cell frequency in the 2x2 table is less than 5).


Secondary Outcome Measures:
  • To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria. [ Time Frame: Three months following completion of radiation therapy phase. ] [ Designated as safety issue: No ]
    To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria.

  • To assess progression-free survival at 2 years [ Time Frame: At two years following completion of radiation phase ] [ Designated as safety issue: No ]
    Progression-free survival at 2 years.

  • To assess overall survival at 2 years. [ Time Frame: At two years following completion of radiation phase ] [ Designated as safety issue: No ]
    To assess overall survival at 2 years.

  • To assess locoregional disease control at 2 years [ Time Frame: At two years following completion of radiation phase ] [ Designated as safety issue: No ]
    To assess locoregional disease control at 2 years

  • 3.5 To assess distant disease control at 2 years. [ Time Frame: At two years following completion of radiation phase ] [ Designated as safety issue: No ]
    3.5 To assess distant disease control at 2 years.

  • Assessment of quality of life outcomes [ Time Frame: Baseline, during therapy and up to two years following completion of radiation phase ] [ Designated as safety issue: No ]
    Serial evaluation of functional quality-of-life, including M. D. Anderson Dysphagia Inventory (MDADI) and Oropharyngeal swallowing efficiency (OPSE) measures of swallowing function, as well as formal sialometric measurement of parotid function.

  • To identify additional toxicity of treatment [ Time Frame: During therapy and up to 5 years following completion of treatment ] [ Designated as safety issue: Yes ]
    To identify additional toxicity of treatment


Enrollment: 2
Study Start Date: August 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chemotherapy non-responders
Patients treated with three cycles neoadjuvant chemotherapy who do not exhibit response to chemotherapy are then allocated to recieve standard dose and schedule radiotherapy.
Drug: chemotherapy
Chemotherapy for three cycles prior to radiotherapy
Other Name: Cisplatin, Carboplatin, Flourouracil, Etoposide
Radiation: radiotherapy
Standard radiotherapy for non-responders vs reduced dose radiotherapy for responders.
Other Name: IMRT, Radiation Therapy
Experimental: Chemotherapy responders
Patients who respond to chemotherapy are treated with reduced dose radiotherapy.
Drug: chemotherapy
Chemotherapy for three cycles prior to radiotherapy
Other Name: Cisplatin, Carboplatin, Flourouracil, Etoposide
Radiation: Reduced dose radiotherapy
Patients who achieve a response to chemotherapy then go on to receive reduced dose radiotherapy.
Other Name: IMRT, Reduced dose radiation therapy

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Tumor tissue available from primary or nodal metastasis for histological analysis.
  • High p16 tumor expression by IHC, or indeterminate p16 expression by IHC and definitively positive detection of high-risk HPV infection by ISH.
  • T-stage = T1-3 or post-tonsillectomy Tx (T1-3).
  • N-stage = N1-2 or Nx (N1-2).
  • Biopsy-confirmed oropharyngeal primary site.
  • Histology = squamous cell carcinoma, basaloid-squamous carcinoma, nasopharyngeal-type squamous carcinoma, adenosquamous carcinoma, or papillary squamous carcinoma.
  • Age > 17 years old.
  • Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC at least 1500 cells/mm3 and platelet count at least 100,000 cells/mm3); adequate hepatic function with bilirubin less than 1.5x ULN (excluding Gilbert's disease); SGOT, SGPT and alkaline phosphatase must be within the normal range to be eligible for study.
  • Creatinine clearance at least 70 ml/min determined by 24 hour collection or nomogram: CrCl male = (140 - age) x (wt in kg)/serum Cr x 72; CrCl female = 0.85 x (CrCl male).
  • Patients must have an untransfused hemoglobin of at least 9.0 grams/dL.
  • Patients should have no serious acute or chronic co-morbid condition, or acute infection, which in the judgment of the attending physician would affect administration of the induction chemotherapy regimens.
  • Patients must sign a study-specific informed consent form.
  • All of the above lab criteria must be verified within 28days of registration.

Exclusion Criteria:

  • Low p16 expressing tumor by IHC, or indeterminate p16 expression by IHC and negative or weak detection of high-risk HPV infection by ISH.
  • TxNx without residual measurable disease, T4, or N3 disease.
  • Significant cigarette smoking history, defined as >10 pack-years total lifetime exposure. Pack years is calculated as # packs smoked per day x # years smoking.
  • Histology other than squamous cell carcinoma.
  • Proven distant metastases (below the clavicle) by clinical or radiographic measures.
  • Karnofsky performance status < 80 or ECOG >1.
  • Prior chemotherapy, within the previous 3 years.
  • Prior radiotherapy to the head and neck.
  • Initial surgical resection rendering the patient clinically and radiologically disease free.
  • Simultaneous primary invasive cancers, excluding superficial non-melanoma skin cancers.
  • Patients with a history of another malignancy (excluding non melanoma skin cancers, and cancers treated > 3 years prior for which patient remains continuously disease free).
  • Men and women of childbearing potential (WOCBP) unwilling to consent to using effective contraception while on treatment and for at least 3 months thereafter. Note: WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for 3 months after the study in such a manner that the risk of pregnancy is minimized.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01525927

Locations
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Sponsors and Collaborators
North Shore Long Island Jewish Health System
Investigators
Principal Investigator: Bhoomi Mehrotra, MD North Shore-LIJ Health System
  More Information

Publications:

Responsible Party: North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier: NCT01525927     History of Changes
Other Study ID Numbers: NSLIJ0844
Study First Received: February 1, 2012
Last Updated: January 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by North Shore Long Island Jewish Health System:
Oropharyngeal Neoplasms
Neoplasms, Oropharyngeal
Oropharynx Neoplasms

Additional relevant MeSH terms:
Neoplasms
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on July 29, 2014