Clinical Trials /

Priming Immunotherapy in Advanced Disease With Radiation

NCT03313804

Description:

This study proposes to treat metastatic non-small cell lung cancer (NSCLC) and head/neck squamous cell cancer (HNSCC) patients who are already initiating an immune checkpoint inhibitor (such as Nivolumab, Atezolizumab or Pembrolizumab) for disease treatment as per FDA approved guidelines. In these patients we will deliver a short-course radiation to a single systemic (non-CNS) site within 14 days of receiving the first dose of immune checkpoint inhibitors. This sequence allows radiation to release tumor antigens from immune inaccessible areas such as necrotic tumor or low perfusion to provide a robust anti-tumor immune response with immune checkpoint inhibitors. The primary objective is to assess six-month progression free survival (PFS) compared to historical control.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Priming Immunotherapy in Advanced Disease With Radiation
  • Official Title: Priming Immunotherapy in Advanced Disease With Radiation

Clinical Trial IDs

  • ORG STUDY ID: MCC-17-MULTI-20-PMC
  • NCT ID: NCT03313804

Conditions

  • Non-small Cell Lung Cancer
  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
Immune checkpoint inhibitorImmune Checkpoint Inhibitor + Radiation

Purpose

This study proposes to treat metastatic non-small cell lung cancer (NSCLC) and head/neck squamous cell cancer (HNSCC) patients who are already initiating an immune checkpoint inhibitor (such as Nivolumab, Atezolizumab or Pembrolizumab) for disease treatment as per FDA approved guidelines. In these patients we will deliver a short-course radiation to a single systemic (non-CNS) site within 14 days of receiving the first dose of immune checkpoint inhibitors. This sequence allows radiation to release tumor antigens from immune inaccessible areas such as necrotic tumor or low perfusion to provide a robust anti-tumor immune response with immune checkpoint inhibitors. The primary objective is to assess six-month progression free survival (PFS) compared to historical control.

Detailed Description

      Subjects with front-line or relapsed NSCLC or relapsed HNSCC who are intended to receive
      standard of care immune checkpoint inhibitors without a contraindication to Stereotactic Body
      Radiation Therapy (SBRT) to a single cancer deposit greater than 1 cm (metastasis or primary
      cancer) will be enrolled. Subjects will receive standard of care (SOC) immune checkpoint
      inhibitors and within 2 weeks of initiation, and will receive either:

        -  SBRT to target to achieve Biological Equivalent Dose (BED) > 100 Gy OR

        -  30 Gy fractionated radiation therapy (RT) delivered as a 3 dimensional (3-D) dose.

      The lesion choice will be made by the treating radiation oncologist and will be directed to a
      single malignant focus (non-CNS) that measures ≥ 1 cm. Essentially, the goals of both
      techniques are the same but SBRT is reserved for lesions that are readily encompassed by a
      single field with large RT fractions in which dose-limiting organs are within safe limits.
    

Trial Arms

NameTypeDescriptionInterventions
Immune Checkpoint Inhibitor + RadiationExperimentalImmune checkpoint inhibitor (Nivolumab OR Pembrolizumab OR Atezolizumab) PLUS Radiation Therapy (Stereotactic Body Radiation Therapy OR fractionated radiation therapy)
  • Immune checkpoint inhibitor

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Eligible for treatment with radiation therapy.

          3. Prior treatment: chemotherapy or radiotherapy or surgery.

               1. Prior chemotherapy or radiation must have concluded ≥ 21 days prior to the start
                  of study treatment.

               2. No limit is placed on prior systemic treatment, but subjects must be eligible for
                  immune checkpoint inhibitors therapy, for an FDA approved indication.

               3. No major surgery within 14 days of start of study treatment.

          4. 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.

          5. Age ≥ 18 years.

          6. Life expectancy ≥ 3 months.

          7. Required initial laboratory values:

               1. Absolute neutrophil count ≥ 1,000/mm3

               2. Platelets ≥ 100,000/mm3

               3. Total bilirubin ≤ 1.5 x ULN

               4. AST and ALT if no hepatic metastasis ≤ 2.5 times x ULN

               5. AST and ALT with hepatic metastasis ≤ 5 x ULN

               6. Creatinine ≤ 1.5 x ULN and Requires CrCl ≥ 60ml/min (per 24-hour urine collection
                  or calculated according to the Cockcroft-Gault formula)

          8. 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.

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

        Exclusion Criteria:

          1. Active clinically serious infection > CTCAE Grade 2.

          2. Serious non-healing wound, ulcer or bone fracture.

          3. Prior treatment with immune checkpoint inhibitors.

          4. 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).

          5. 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-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.

          6. Participants may not have uncontrolled inter-current illness. This includes, but is
             not limited to: ongoing or active infection; symptomatic congestive heart failure
             (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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The primary study endpoint is 6-month progression-free survival.
Time Frame:6-months post enrollment
Safety Issue:
Description:Progression-free survival will be calculated as time from enrollment in the study to progression at 6-months post enrollment.

Secondary Outcome Measures

Measure:Percentage of (programmed death) PD-1+ CD4+ T (helper) cells and PD-1+ CD8+ T (cytotoxic) cells prior to treatment versus with concurrent treatment.
Time Frame:Assessed at specified points--1) prior to each cycle of therapy for 4 cycles (one cycle equals 6 weeks) 2) at disease progression (date first progression post-randomization, assessed up to 3 years) 3) when participant is off-study, assessed up to 3 years
Safety Issue:
Description:
Measure:Percentage of CD8+ T-cells that are gamma-interferon positive during treatment.
Time Frame:Assessed at specified points--1) prior to each cycle of therapy for 4 cycles (one cycle equals 6 weeks) 2) at disease progression (date first progression post-randomization, assessed up to 3 years) 3) when participant is off-study, assessed up to 3 years
Safety Issue:
Description:
Measure:Percentage PD-L1+ CD4+ and PD-L1+ CD8+ T-cell expression differences during treatment
Time Frame:Assessed at specified points--1) prior to each cycle of therapy for 4 cycles (one cycle equals 6 weeks) 2) at disease progression (date first progression post-randomization, assessed up to 3 years) 3) when participant is off-study, assessed up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:John L. Villano, MD, PhD

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