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Nivolumab, Pembrolizumab, or Atezolizumab and Standard Radiation Therapy or Stereotactic Body Radiation Therapy in Treating Patients with Advanced or Metastatic Non-small Cell Lung Cancer or Head and Neck Squamous Cell Carcinoma

Trial Status: Active

This phase II trial studies how well nivolumab, pembrolizumab, or atezolizumab and standard radiation therapy or stereotactic body radiation therapy works in treating patients with non-small cell lung cancer or head and neck squamous cell carcinoma that has progressed or metastasized or is no longer responding to treatment. Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving a short-course of stereotactic body radiation therapy or standard radiation therapy after starting treatment with nivolumab, pembrolizumab, or atezolizumab may work to kill tumor cells by releasing tumor antigens from immune inaccessible areas to provide an anti-tumor immune response.

Inclusion Criteria

  • Histologically proven advanced or metastatic non-small cell lung cancer or squamous cell carcinoma head and neck with tumor at least 1 cm in size
  • Eligible for treatment with radiation therapy
  • Prior treatment: chemotherapy or radiotherapy or surgery
  • Prior chemotherapy or radiation must have concluded >= 21 days prior to the start of study treatment (exception- study treatment can start within 1-2 days following GKS [gamma knife surgery] as long as patient is not experiencing adverse events [AE’s] related to GKS)
  • No limit is placed on prior systemic treatment, but subjects must be eligible for immune checkpoint inhibitors therapy, for a Food and Drug Administration (FDA) approved indication
  • No major surgery within 14 days of start of study treatment
  • No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for the past 3 years
  • Life expectancy >= 3 months
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) if no hepatic metastasis =< 2.5 times x ULN
  • AST and ALT with hepatic metastasis =< 5 x ULN
  • Creatinine =< 1.5 x ULN and/or requires creatinine clearance (CrCl) >= 30 ml/min (per 24-hour urine collection or calculated according to the Cockcroft-Gault formula)
  • Non pregnant and non-nursing women; women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; subjects should use adequate birth control for at least 3 months after the last administration of immune checkpoint inhibitors
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
  • Serious non-healing wound, ulcer or bone fracture
  • Prior treatment with immune checkpoint inhibitors
  • Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor (e.g., uncontrolled immunologic disorders, active hepatitis, active colitis, active pneumonitis, uncontrolled/active hormone gland problems - including thyroid, pituitary, adrenal glands and pancreas)
  • Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury within 14 days prior to registration or those patients who receive a non-central nervous system (CNS) minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration; there is no waiting period for central line placement; there is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain
  • Participants may not have uncontrolled inter-current illness; this includes, but is not limited to: ongoing or active infection; symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV); unstable angina pectoris or new onset angina that began within the last 3 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; or thrombotic/embolic events such as cerebrovascular accident, including transient ischemic attacks within the past 6 months; uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management; known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C; known grade 3 or 4 neurotoxicity

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: ACTIVE
Contact: John Lee Villano
Phone: 859-323-0405

PRIMARY OBJECTIVES:

I. Single arm phase II trial to assess six-month (mo) progression free survival (PFS) compared to historical control.

SECONDARY OBJECTIVES:

I. The safety and tolerability of the immune checkpoint inhibitor administered prior to radiation therapy will be evaluated.

II. Overall survival and 1-year PFS will be evaluated.

III. Evaluation of PD-1 expression and activation of cytotoxic T-cells.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes every 2 or 4 weeks, pembrolizumab IV every 3 weeks, or atezolizumab IV every 3 weeks per the discretion of the treating physician. Cycles repeat every 84 days in the absence of disease progression or unacceptable toxicity. Beginning within 14 days of starting nivolumab, pembrolizumab, or atezolizumab treatment, patients undergo standard radiation therapy (RT) over 10 fractions or stereotactic body radiation therapy (SBRT) over 1-5 fractions per the discretion of the treating radiation oncologist.

After completion of study treatment, patients are followed up for 3 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Kentucky / Markey Cancer Center

Principal Investigator
John Lee Villano

  • Primary ID MCC-17-MULTI-20-PMC
  • Secondary IDs NCI-2017-01887, 17-0595-F6A
  • Clinicaltrials.gov ID NCT03313804