Combination Chemotherapy and Radiation Therapy In Treating Patients With Locally Advanced Stage III-IV Squamous Cell Cancer of the Oropharynx and Human Papillomavirus Infection

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IITreatmentActive18 and over10-038
NCI-2010-02212, NCT01221753

Trial Description

Summary

This phase II trial studies how well giving combination chemotherapy together with radiation therapy works in treating patients with locally advanced stage III-IV squamous cell cancer of the oropharynx and human papillomavirus (HPV) infection. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil (5-FU), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine rate of local-regional control at 2 years in patients with advanced HPV related oropharynx cancer or unknown primary.

SECONDARY OBJECTIVES:

I. To determine Progression Free Survival at 2 and 5 years.

II. To determine Overall Survival at 2 and 5 years.

III. To assess acute toxicity and long term toxicity of reduced radiation dose at 2 and 5 years.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive docetaxel intravenously (IV) over 60 minutes and cisplatin IV over 60 minutes (or carboplatin IV over 30-45 minutes) on day 1 and 5-FU IV continuously over 24 hours on days 1-4. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CHEMORADIOTHERAPY: Patients receive cetuximab IV over 60-120 minutes (or panitumumab IV over 30-60 minutes) and carboplatin IV once weekly. Patients also undergo intensity-modulated radiation therapy (IMRT) once daily, for 5 days a week. Treatment continues for 6-7 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up every 4 to 6 weeks for 3 months, then every 3 months for 2 years, and then periodically for 3 years.

Eligibility Criteria

Inclusion Criteria:

Participants must have histologically or cytologically confirmed squamous cell carcinoma of the oropharynx or unknown primary that is high risk human papillomavirus (HPV) positive as determined by p16 immunohistochemistry (IHC) testing and/or HPV in situ hybridization (ISH) / polymerase chain reaction (PCR)

Stage 3 or 4 disease without evidence of distant metastases

At least one evaluable or uni- or bi-dimensionally measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1criteria; (patients whose only nodal disease is cystic and not positron emission tomography [PET]-avid are not eligible)

No previous surgery, radiation therapy or chemotherapy for squamous cell carcinoma of the head and neck (SSCHN) (other than biopsy or tonsillectomy) is allowed at time of study entry

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

No active alcohol addiction (as assessed by medical caregiver)

Participants must have adequate bone marrow, hepatic and renal function

Neutrophil count >= 1.5 x 10^9/l

Platelet count >= 100 x 10^9/l

Hemoglobin >= 10 g/dl

Renal function: >= 60 ml/min (actual or calculated by the Cockcroft-Gault method)

Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment

Total Bilirubin =< institutional upper level of normal (ULN)

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and Alkaline Phosphatase (ALP) must be within the range allowing for eligibility: ALP normal AND AST or ALT =< 5 x ULN; ALP =< 3.5 x ULN AND AST or ALT =< 1.5 x ULN; OR ALP =< 5 x ULN AND ALT or AST =< ULN

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Pregnant or breast feeding women, or women and men of childbearing potential not willing to use adequate contraception while on treatment and for at least 3 months thereafter

Previous or current malignancies at other sites, with the exception of adequately treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the skin, thyroid cancer, or other cancer curatively treated by surgery and with no evidence of disease for at least 5 years

Symptomatic peripheral neuropathy >= grade 2 by National Cancer Institute (NCI) Common Terminology Criteria (NCI-CTC) version 4

Symptomatic altered hearing > grade 2 by NCI-CTCv4 criteria

Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry

History of significant neurologic or psychiatric disorders including dementia or seizures

Active clinically significant uncontrolled infection

Active peptic ulcer disease defined as unhealed or clinically active

Hypercalcemia

Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis

Chronic Obstructive Pulmonary Disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis; this does not include obstruction from tumor

Autoimmune disease requiring therapy, prior organ transplant, or human immunodeficiency virus (HIV) infection

Interstitial lung disease

Patients that have experienced an involuntary weight loss of more than 25% of their body weight in the 2 months preceding study entry

Concurrent treatment with any other anticancer therapy

Participation in an investigational trial within 30 days of study entry

Patients whose only nodal disease is cystic and not PET-avid

Patients who have a smoking history of > 10 pack-years

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Dana-Farber Harvard Cancer Center

  • National Cancer Institute
Robert I. Haddad, Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01221753

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.