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Clinical Trial 20282

Cancer Type: Head & Neck
Study Type: Treatment
NCT#: NCT03952585

Phase: Phase II/III
Principal Investigator: Caudell, Jimmy

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or 1-800-679-0775 Learn More

Overview

Study Title

A Randomized Phase II/III Trial of De-Intensified Radiation Therapy for Patients with Early-Stage, P16 Positive, Non-Smoking Associated Oropharyngeal Cancer

Summary

This phase II/III trial studies how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and may not have spread to other parts of the body (early-stage), and is not associated with smoking. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, 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. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see if a reduced dose of radiation therapy and nivolumab works as well as standard dose radiation therapy and cisplatin in treating patients with oropharyngeal cancer.

Objective

Primary Objective Phase II To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with cisplatin or concurrent reduced-dose radiation therapy with nivolumab to the current standard of care (standard-dose RT with cisplatin). Phase III To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MDADI of concurrent reduced-dose radiation with cisplatin or concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). Secondary Objectives -To compare patterns of failure (local and regional relapse versus distant) and overall survival between each experimental arm and the control arm; -To assess long term PFS, overall survival, and toxicity between each experimental arm and the control arm; -To determine acute and late toxicity profiles as measured by the CTCAE; -To explore the symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the PRO-CTCAE; -To compare changes in patient-reported outcomes (HHIA-S, EORTC-QLQ30) between each experimental arm and the control arm; -To assess the association of FDG-PET/CT at baseline with locoregional control and PFS; -To estimate the negative predictive value of the 12-14 weeks post-RT FDG-PET/CT in terms of locoregional control rates and PFS rates at 1 and 2 years.

Treatments

Therapies

Chemotherapy (NOS); Immunotherapy; Radiotherapy

Medications

BMS-936558 (Nivolumab); Nivolumab (Opdivo); cisplatin ()

Inclusion Criteria

Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma but not neuroendocrine phenotype) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.

Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Simple tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving => P16-positive based on local site immunohistochemical tissue staining (defined as greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining of tumor cells). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue.

Clinical stage T1-2, N1, M0 (American Joint Committee on Cancer [AJCC], 8th edition [ed.]) or T3, N0-N1, M0 (AJCC, 8th ed.) including no distant metastases based on diagnostic workup outlined per protocol.

Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. The following formula is used to calculate the pack-years during the periods of smoking in the patient's life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history

Adequate organ function as defined per protocol.

Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment for the hepatitis, they are eligible if they have an undetectable HCV viral load. Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy

For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 24 hours prior to registration

Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception during and after treatment

Only English, Spanish, or French speaking patients are eligible to participate as these are the only languages for which the mandatory dysphagia-related patient reported instrument (MDADI) is available

Other criteria apply

Exclusion Criteria

Clinical stages T0; T4; T1-2, N0; or any N2 (AJCC, 8th ed)

Recurrent disease

Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles

Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16-positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas

Carcinoma of the neck of unknown primary site origin (T0 is ineligible, even if p16-positive)

Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane

Supraclavicular nodes, defined as nodes centered below the level of the cricoid cartilage.

Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed

Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (of note, the exclusion applies only for invasive cancers such that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)

Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable

Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways

History of severe hypersensitivity reaction to any monoclonal antibody.

Severe, active co-morbidity as defined per protocol.

Patients who are pregnant, nursing, or expecting to conceive or father children

Prior allergic reaction to cisplatin

Other exclusions apply

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