Docetaxel and Radiation Therapy in Treating Patients With HPV Positive Oropharynx Cancer

Oropharyngeal Squamous Cell Carcinoma Clinical Trial

Official title:

DART-HPV: A Phase III Evaluation of De-Escalated Adjuvant Radiation Therapy for HPV-Associated Oropharynx Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03421470
• Other study ID #: MC1675
• Secondary ID: NCI-2017-02365MC
• Status: Recruiting
• Phase: Phase 3
• First received: December 29, 2017
• Last updated: January 29, 2018
• Start date: October 3, 2016
• Est. completion date: October 15, 2021

Study information

• Verified date: December 2017
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies docetaxel and radiation therapy and how well it works compared to standard of care therapy. Drugs used in chemotherapy, such as docetaxel, 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. It is not known if giving docetaxel with radiation therapy may kill more tumor cells than standard therapy.

Description:

PRIMARY OBJECTIVES:

I. To compare the rates and severity of late grade 3-5 toxicities and percutaneous endoscopic gastrostomy (PEG) tube dependence between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.

SECONDARY OBJECTIVES:

I. To assess the cumulative incidence of local/regional failure at 2 years after study registration for patients treated with DART versus (vs) standard therapy.

II. To compare overall survival, disease-free survival, and distant failure associated with DART vs standard treatment.

III. To compare the overall quality of life (QOL) between DART and standard adjuvant therapy at 1-year post-treatment as measured by Functional Assessment of Cancer Therapy (FACT) Head and Neck (H&N) and European Organization for Research and Treatment of Cancer (EORTC) H&N quality of life questionnaire (QLQ) 35.

TERTIARY OBJECTIVES:

I. To determine the genetic alterations of oropharynx tumor specimens and the detection rate of corresponding circulating deoxyribonucleic acid (DNA) in the pre-surgical, post-surgical, and post-radiation blood of oropharynx cancer patients.

II. To investigate the usefulness of immunologic biomarkers in predicting progression free survival.

III. To establish a patient derived xenograft panel from representative oropharynx patients.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (DART): Patients undergo 20 fractions of intensity-modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) twice daily (BID) on days 1-12 (Monday - Friday), and receive docetaxel intravenously (IV) over 1 hour on days 1 and 8 in the absence of disease progression or unacceptable toxicity.

ARM II (STANDARD OF CARE): Patients undergo 30 fractions of IMRT or IGRT daily on days 1-40 (Monday - Friday), and receive cisplatin IV weekly around days 1, 8, 15, 22, 29 and 36 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3 days post-radiation therapy, at 1 month, every 3 months for 2 years, every 6 months for 1 year, then annually for 2 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 214
• Est. completion date: October 15, 2021
• Est. primary completion date: October 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• PRE-REGISTRATION (OPTIONAL)

• Provide written informed consent

• Submission of research blood draw and/or tumor sample

• REGISTRATION

• Histological confirmation of human papillomavirus (HPV) positive (+) squamous cell carcinoma of the oropharynx; HPV positivity will be defined as positive staining for p16 on immunohistochemistry (IHC)

• Gross total surgical resection with curative intent of the primary tumor and at least unilateral neck dissection within 7 weeks of registration

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

• Absence of distant metastases on standard diagnostic work-up =< 16 weeks prior to registration; (chest computed tomography [CT], chest x-ray [CXR], or positron emission tomography [PET]/CT)

• Must have one of the following risk factors:

• Lymph node > 3 cm

• 2 or more positive lymph nodes

• Perineural invasion

• Lymphovascular space invasion

• T3 or primary disease

• Lymph node extracapsular extension

• Obtained =< 35 days prior to registration: absolute neutrophil count (ANC) >= 1500/mm^3

• Obtained =< 35 days prior to registration: platelet count >= 100,000/mm^3

• Obtained =< 35 days prior to registration: hemoglobin >= 8.0g/dL

• Obtained =< 35 days prior to registration: creatinine =< 1.5 mg/dL or creatinine clearance >= 50 mL/min

• Obtained =< 35 days prior to registration: total or direct bilirubin < 2 x institutional upper limit of normal (ULN)

• Obtained =< 35 days prior to registration: aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 x institutional ULN

• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

• Ability to complete questionnaire(s) by themselves or with assistance

• Provide informed written consent

• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer

• Prior history of radiation therapy to the affected site

• History of connective tissue disorders such as rheumatoid arthritis, lupus, or Sjogren?s disease

• Presence of any of the following risk factors after surgery:

• Any positive surgical margin.

• Adenopathy below the clavicles

• Prior systemic chemotherapy

• History of allergic reaction to docetaxel

• Receiving any medications or substances which in the opinion of the investigators would interfere with treatment; examples could include strong inhibitors of CYP3A4 at oncologist discretion

• Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy

• If there are 3 or more attempts by the surgeon to clear margins, patient is not eligible for study

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Human Papillomavirus Positive
• Oropharyngeal Neoplasms
• Oropharyngeal Squamous Cell Carcinoma

Intervention

Drug:
• Cisplatin
Given IV
• Docetaxel
Given IV

Radiation:
• Image Guided Radiation Therapy
Undergo IGRT
• Intensity-Modulated Radiation Therapy
Undergo IMRT

Other:
• Laboratory Biomarker Analysis
Correlative studies

Procedure:
• Quality-of-Life Assessment
Ancillary studies

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of late adverse events (>= 3 months)		Up to 2 years
Secondary	Disease-free survival (DFS)	DFS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.	From randomization to the first of either disease recurrence or death from any cause, assessed up to 5 years
Secondary	Distant failure rates	Will be estimated by the competing risk method (Gooley, et al.), where the competing risks are local/regional failures and deaths from other causes (i.e. deaths from local/regional failure or non-oropharynx cancer).	2 years
Secondary	Incidence of local/regional failure	Will be estimated by the competing risk method (Gooley, et al.), where the competing risks are distant failures and deaths from other causes (i.e. deaths from distant failure or non-oropharynx cancer).	2 years after registration
Secondary	Overall survival (OS)	OS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.	From randomization to death from any cause, assessed up to 5 years
Secondary	Quality of life (QOL) between DART and standard adjuvant therapy	Will be measured by FACT Head & Neck questionnaire	1 year post-treatment
Secondary	Quality of life (QOL) between DART and standard adjuvant therapy	Will be measured by European organization for research and treatment of cancer (EORTC) quality of life questionnaire (QLQ)-head and neck (H&N) 35 questionnaire	1 year post-treatment
Secondary	Swallowing studies	Swallowing will be scored (yes, no) for aspiration, penetration, velopharyngeal incompetence, epiglottic eversion, tongue base retraction, and pharyngeal swallow response using the metric outlined by Eisbruch et al. (Eisbruch A, Teresa L, Bradford CR, et al.) The swallowing questions will be explored descriptively to detect patterns and substantial changes over time between arms.	Baseline
Secondary	Swallowing studies	Swallowing will be scored (yes, no) for aspiration, penetration, velopharyngeal incompetence, epiglottic eversion, tongue base retraction, and pharyngeal swallow response using the metric outlined by Eisbruch et al. (Eisbruch A, Teresa L, Bradford CR, et al.) The swallowing questions will be explored descriptively to detect patterns and substantial changes over time between arms.	1 month after the completion of protocol XRT
Secondary	Swallowing studies	Swallowing will be scored (yes, no) for aspiration, penetration, velopharyngeal incompetence, epiglottic eversion, tongue base retraction, and pharyngeal swallow response using the metric outlined by Eisbruch et al. (Eisbruch A, Teresa L, Bradford CR, et al.) The swallowing questions will be explored descriptively to detect patterns and substantial changes over time between arms.	12 months after the completion of protocol XRT