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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01525927
Recruitment Status : Terminated (Principal Investigator left institution. IRB approval lapsed.)
First Posted : February 3, 2012
Results First Posted : September 30, 2015
Last Update Posted : December 19, 2017
Information provided by (Responsible Party):
Northwell Health

Brief Summary:
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 or disease Intervention/treatment Phase
Oropharyngeal Neoplasms Drug: chemotherapy Radiation: radiotherapy Radiation: Reduced dose radiotherapy Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : August 2010
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Response (CR+PR) Status at 3 Months Post-therapy [ Time Frame: 3 months following completion of radiation phase ]

    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).

    Zero (0) participants analyzed

Secondary Outcome Measures :
  1. To Define Objective Tumor Response Rates to Induction Chemotherapy and to Subsequent Radiation-based Treatment. [ Time Frame: Three months following completion of radiation therapy phase. ]
    To define objective tumor response rates to induction chemotherapy and to subsequent radiation-based treatment, per RESIST version 1.1 criteria.

  2. Progression-free Survival at 2 Years [ Time Frame: At two years following completion of radiation phase ]
    assess Progression-free survival at 2 years.

  3. Assess Overall Survival at 2 Years. [ Time Frame: At two years following completion of radiation phase ]
    To assess overall survival at 2 years.

  4. Assess Locoregional Disease Control at 2 Years [ Time Frame: At two years following completion of radiation phase ]
    To assess locoregional disease control at 2 years

  5. Assess Distant Disease Control at 2 Years. [ Time Frame: At two years following completion of radiation phase ]
    3.5 To assess distant disease control at 2 years.

  6. Assessment of Quality of Life Outcomes [ Time Frame: Baseline, during therapy and up to two years following completion of radiation phase ]
    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.

  7. Identify Additional Toxicity of Treatment [ Time Frame: During therapy and up to 5 years following completion of treatment ]
    To identify additional toxicity of treatment

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01525927

United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Sponsors and Collaborators
Northwell Health
Principal Investigator: Bhoomi Mehrotra, MD Northwell Health


Responsible Party: Northwell Health Identifier: NCT01525927     History of Changes
Other Study ID Numbers: NSLIJ0844
First Posted: February 3, 2012    Key Record Dates
Results First Posted: September 30, 2015
Last Update Posted: December 19, 2017
Last Verified: November 2017

Keywords provided by Northwell Health:
Oropharyngeal Neoplasms
Neoplasms, Oropharyngeal
Oropharynx Neoplasms

Additional relevant MeSH terms:
Oropharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases