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

NCT01525927 | Terminated Phase 2 Results DMC

• 1 other identifier: NSLIJ0844
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Oropharyngeal Neoplasms

Keywords

Oropharyngeal Neoplasms; Neoplasms, Oropharyngeal; Oropharynx Neoplasms

Outcome Measures

Primary Outcomes (1)

• Response (CR+PR) Status at 3 Months Post-therapy

  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

  3 months following completion of radiation phase

Secondary Outcomes (7)

• To Define Objective Tumor Response Rates to Induction Chemotherapy and to Subsequent Radiation-based Treatment.

  Three months following completion of radiation therapy phase.

• Progression-free Survival at 2 Years

  At two years following completion of radiation phase

• Assess Overall Survival at 2 Years.

  At two years following completion of radiation phase

• Assess Locoregional Disease Control at 2 Years

  At two years following completion of radiation phase

• Assess Distant Disease Control at 2 Years.

  At two years following completion of radiation phase

Study Arms (2)

Chemotherapy non-responders

ACTIVE COMPARATOR

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; Radiation: radiotherapy

Chemotherapy responders

EXPERIMENTAL

Patients who respond to chemotherapy are treated with reduced dose radiotherapy.

Drug: chemotherapy; Radiation: Reduced dose radiotherapy

Interventions

chemotherapy DRUG

Chemotherapy for three cycles prior to radiotherapy

Also known as: Cisplatin, Carboplatin, Flourouracil, Etoposide

Chemotherapy non-responders; Chemotherapy responders

radiotherapy RADIATION

Standard radiotherapy for non-responders vs reduced dose radiotherapy for responders.

Also known as: IMRT, Radiation Therapy

Chemotherapy non-responders

Reduced dose radiotherapy RADIATION

Patients who achieve a response to chemotherapy then go on to receive reduced dose radiotherapy.

Also known as: IMRT, Reduced dose radiation therapy

Chemotherapy responders

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Related Publications (16)

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MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Drug Therapy; Cisplatin; Carboplatin; Etoposide; Radiotherapy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Limitations and Caveats

Study terminated , PI left the institution, no data analyzed

Results Point of Contact

• Title: Jeffrey Revello Sr. Administrative Manager
• Organization: North Shore LIJ Cancer Institute

jrevello@nshs.edu

516 734 7629

Study Officials

• Bhoomi Mehrotra, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 3, 2012
• Study Start: August 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 19, 2017
• Results First Posted: September 30, 2015

Record last verified: 2017-11

Locations

US (1)