A Prospective Trail of Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for the Treatment of Metastatic Lung Cancer: SBRT Sensitization of the Programmed Death-1 (PD-1) Effect
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Metastatic Nonsmall Cell Lung Cancer
- Sponsor
- Crozer-Keystone Health System
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent.
Detailed Description
Blockade of the PD-1/PD-L1 T-cell checkpoint pathway is an effective and well tolerated approach to stimulating the immune response which is a critical option in the treatment of metastatic NSCLC. However, progression free survival (PFS) is increased by only 2-4 months and median overall survival (OS) by 3-9 months. There is compelling evidence that PFS is increased up to 3 fold and OS by 2 fold in patients receiving a course of radiation therapy while on immunotherapy. Radiotherapy is known to induce immunogenic tumor cell death and upregulation of dendritic cells and antigen presentation leading to activation of cytotoxic T-Cells. Dramatic T-cell activation has been demonstrated where tumor regression occurs outside the radiation treatment field in a phenomenon termed the abscopal effect and is associated with high dose radiation delivered via SBRT. As such, SBRT activation of T-cells could be complementary to immunotherapy and enhance T-cell mediated killing via PD-L1 blockade which could lead to lasting and durable tumor response with improved progression free survival and overall survival.
Investigators
Rachelle Lanciano M.D.
Principal Investigator
Crozer-Keystone Health System
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed Stage IV NSCLC according to the 7th AJCC staging manual.
- •Eligible for an immunotherapy agent. Patients who progress after drug therapy (3 months) for ALK, EGFR or ROS mutation positive lung cancer are eligible.
- •At least 2 lesions that are safely amenable to SBRT. ECOG \<=
- •At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment or at least 1 lesion with FDG avidity and CT correlate that can be monitored for PET-CT response by SUV Max increase or decrease.
- •Normal Hepatic and renal function.
- •Bone marrow reserve:
- •ANC ≥ 1.5 x 109/L
- •Hemoglobin ≥9.0 g/dL
- •Platelet count ≥75 x 109/L
- •Ability to comply with follow-up visits and evaluations, treatment planning and studies and other study related procedures and visits.
Exclusion Criteria
- •Patients with active CNS metastases
- •Active, known or suspected auto-immune disease.
- •Patients with medical conditions that require systemic immunosuppression.
- •Patients with a history of interstitial lung disease.
- •Prior treatment with immune checkpoint inhibitors/immonotherapy.
- •Other active malignancy requiring intervention.
- •Prior lung radiation, with the only metastatic targets in the lungs.
- •Unresolved toxicity from prior chemotherapy or anti-cancer treatment.
- •Current or prior enrollment in clinical trial with an investigational drug within 4 weeks.
- •Pregnancy or positive pregnancy test.
Outcomes
Primary Outcomes
Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
Time Frame: 0-15 weeks
Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.
Overall Survival
Time Frame: 24 months
Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)
Secondary Outcomes
- Local Control(0-24 Months)
- Impact of Tumor Burden(24 Months)
- Progression Free Survival(3-24 Months)
- Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.(6-24 Months)