Combination Chemotherapy and Radiation Therapy in Treating Patients with Locally Advanced HPV Positive Oropharynx Cancer
This phase II trial studies how well combination chemotherapy followed by reduced dose chemoradiation therapy works in curing patients with locally advanced human papillomavirus (HPV) positive oropharynx cancer. Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving combination chemotherapy prior to chemoradiation therapy may result in be less early and late toxicity and side effects then standard chemoradiotherapy in HPV positive oropharynx cancer as there will be fewer side effects.
Inclusion Criteria
- Participants must have histologically or cytologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, supraglottic larynx, nasal cavity, unknown primary, or nasopharynx that is p16 and HPV positive; tissue or cytology from the primary site or lymph node must be available for biomarker studies and for polymerase chain reaction (PCR) testing; immunohistochemistry (IHC) must be performed in a lab verified by the central laboratory or the slides must be available for review by the central laboratory (Zhang, MSSM) and PCR must be done in the central laboratory prior to radiotherapy; HPV PCR must be performed and results available for reduced dose therapy after induction. * Patients who are on the Quarterback Trial when Quarterback 2 is activated and who have been randomized to radiotherapy arm will be asked to transfer to this trial and receive the Quarterback 2 defined radiotherapy
- Stage 3 or 4 disease without evidence of distant metastases
- At least one clinically evaluable or uni- or bi-dimensionally measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
- 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
- Performance status of 0 or 1
- No active alcohol addiction (as assessed by medical caregiver and defined as at least 6 months without activity)
- Neutrophil count >= 1.5 x 10^9/l at cycle 1 day 1 of docetaxel cisplatin and 5-FU (TPF)
- Platelet count >= 100 x 10^9/l at cycle 1 day 1 of TPF
- Hemoglobin >= 10 g/dl at cycle 1 day 1 of TPF
- Renal function: >= 60 ml/min (actual or calculated by the Cockcroft-Gault method) or a creatinine =< the upper limits of normal at cycle 1 day 1 of TPF
- Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment
- Total Bilirubin =< institutional upper level of normal (ULN) at cycle 1 day 1 of TPF
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and alkaline phosphatase must be within the range allowing for eligibility at cycle 1 day 1 of TPF: * Alkaline (Alk) Phosphate (PHOS) =< upper limit of normal (ULN); AST or ALT =< ULN: Eligible * ALK PHOS =< ULN; AST or ALT > 1x but =< 1.5x: Eligible * ALK PHOS =< ULN; AST or ALT > 1.5x but =< 5x: Eligible * ALK PHOS =< ULN; AST or ALT > 5x ULN: Ineligible * ALK PHOS > 1x but =< 2.5x; AST or ALT >1x but =< 2.5x; AST or ALT =< ULN: Eligible * ALK PHOS > 1x but =< 2.5x; AST or ALT > 1x but =< 1.5x: Eligible * ALK PHOS > 1x but =< 2.5x; AST or ALT > 1.5x but =< 5x: Ineligible * ALK PHOS > 1x but =< 2.5x; AST or ALT > 5x ULN: Ineligible * ALK PHOS > 2.5x but =< 5x; AST or ALT =< ULN: Eligible * ALK PHOS > 2.5x but =< 5x; AST or ALT > 1x but =< 1.5x: Ineligible * ALK PHOS > 2.5x but =< 5x; AST or ALT > 1.5x but =< 5x: Ineligible * ALK PHOS > 2.5x but =< 5x; AST or ALT > 5x ULN: Ineligible * ALK PHOS > 5 ULN; AST or ALT =< ULN: Ineligible * ALK PHOS > 5 ULN; AST or ALT > 1x but =< 1.5x: Ineligible * ALK PHOS > 5 ULN; AST or ALT > 1.5x but =< 5x: Ineligible * ALK PHOS > 5 ULN; AST or ALT > 5x ULN: Ineligible
- Ability to understand and the willingness to sign a written informed consent document
- Patients with Gilbert’s disease and absent hepatic pathology by history and clinical assessment maybe treated on study with bilirubin > the ULN for the institution if other liver function studies are within the normal range
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 current 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-CTC version (v)4 criteria; these patients can be entered by substituting carboplatin for cisplatin with an area under the curve (AUC) of 6.0
- Other serious illnesses or medical conditions including but not limited to: * 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 * Hepatitis C by history, and confirmed by serology
- 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 therapeutic drug trial within 30 days of study entry
- Active smoking or a cumulative pack year history of > 20 pack years, active smoking is (defined as >= 1 cigarette per day) within the last 5 years
Additional locations may be listed on ClinicalTrials.gov for NCT02945631.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine the rate of progression free survival (PFS) at 3 years in patients with advanced HPV related oropharynx cancer, hypopharynx, nasopharynx cancer or unknown primary treated with sequential therapy and reduced dose chemoradiation therapy (CRT).
II. To determine the comparative rate of local-regional control (LRC) at 3 years in patients with advanced HPV related oropharynx cancer or unknown primary treated with sequential therapy and reduced dose CRT.
SECONDARY OBJECTIVES:
I. To determine the comparative rate of local-regional control (LRC) over 5 years in patients with advanced HPV related oropharynx cancer or unknown primary treated sequential therapy and reduced dose CRT.
II. To determine the comparative rate of progression free survival (PFS) over 5 years in patients with advanced HPV related oropharynx cancer or unknown primary treated with sequential therapy and standard dose CRT.
III. To determine overall survival (OS) at 3 and 5 years treated with reduced dose CRT.
IV. To establish the acute toxicity in patients treated with reduced dose CRT.
V. To establish long term toxicity of patients treated with reduced dose CRT at 2, 3 and 5 years.
VI. To determine biomarkers predictive of failure with reduced dose CRT.
VII. To establish a tumor tissue, germline deoxyribonucleic acid (DNA), peripheral blood and plasma bank for future studies of the protocol selected and treated populations.
OUTLINE:
INDUCTION CHEMOTHERAPY: Patients receive docetaxel intravenously (IV) over 60 minutes on day 1, cisplatin IV over 1-3 hours on day 1, and 5-fluorouracil IV continuous infusion over 4 days on days 1-4 of cycles 1-3, (or carboplatin as a substitute for cisplatin IV over 30-45 minutes on day 1). Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Following induction chemotherapy, patients are re-assessed for response to treatment and assigned to 1 of 2 arms.
Arm I: Beginning 4-6 weeks after cycle 3 day 1, patients with complete response or partial response receive carboplatin IV over 30 minutes once a week and undergo low dose intensity-modulated radiation therapy 5 days per week to a total dose of 5600 cGy. Treatment repeats every week for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Arm II: Beginning 4-6 weeks after cycle 3 day 1, patients with no response or progressive disease may undergo surgery (depending on their primary site and overall medical condition) or receive carboplatin IV over 30 minutes once a week and undergo standard dose intensity-modulated radiation therapy 5 days per week to a total dose of 5600 cGy. Treatment repeats every week for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1-2 months for the first year, every 2-3 months for the second year, every 3-4 months for the third year, and then biannually for up to 5 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationIcahn School of Medicine at Mount Sinai
Principal InvestigatorMarshall Roy Posner
- Primary ID16-0609
- Secondary IDsNCI-2017-01027
- ClinicalTrials.gov IDNCT02945631