Clinical trial NCT03825510: Immunotherapy SBRT Sensitization of the Programmed Death-1 (PD-1) Effect
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Nonsmall Cell Lung Cancer
Non Small Cell Lung Cancer
Keywords: Opdivo, Keytruda, Cyberknife
Lead sponsor: Crozer-Keystone Health System
Sponsor class: OTHER
Collaborators: name: Saint Peters University Hospital
name: Community Medical Center, Toms River, NJ
First posted: 2019-01-31
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 \<=2.
* 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:

  1. ANC ≥ 1.5 x 109/L
  2. Hemoglobin ≥9.0 g/dL
  3. 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.
* Ability to sign informed consent.

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.

Primary outcomes:
measure: Overall Survival
timeFrame: 24 months
measure: Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0
timeFrame: 0-15 weeks
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 3-24 Months
measure: Local Control
timeFrame: 0-24 Months
measure: Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.
timeFrame: 6-24 Months
measure: Impact of Tumor Burden
timeFrame: 24 Months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Philadelphia CyberKnife
state: Pennsylvania
Study officials:
References: