SCION: SABR and Checkpoint Inhibition of NSCLC

NCT04944173 | Withdrawn Phase 2 DMC

• 2 other identifiers: H21-00994OZM-119
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

The SCION Trial is a clinical trial in patients with early stage non-small cell lung cancer. The purpose of the trial is to investigate whether it is safe and effective to combine standard radiation treatment with a drug called durvalumab, a type of immunotherapy. In addition, the study will use a blood test to look for cancer cell DNA to determine how long treatment with durvalumab should last. Both the use of durvalumab and the use of the blood test are new strategies for managing early stage non-small cell lung cancer.

Conditions

Non Small Cell Lung Cancer; Carcinoma, Non-Small-Cell Lung; Non-small Cell Lung Cancer Stage I; Lung Cancer; Lung Cancer Stage I; Lung Adenocarcinoma, Stage I; Lung Squamous Cell Carcinoma Stage I

Keywords

durvalumab; Imfinzi; MEDI4736; MEDI-4736; Circulating Tumor DNA; Cell-Free Tumor DNA; Minimal Residual Disease; Stereotactic Radiation Therapy; Stereotactic Body Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Risk of Relapse

  Fraction of subjects experiencing relapse at 18 months following initial therapy

  18 months

Secondary Outcomes (13)

• Radiographic Response by RECIST criteria

  6 months (CT) and 12 months (PET/CT)

• Local Relapse

  18 months

• Regional Nodal Relapse

  18 months

• Distant Metastatic Relapse

  18 months

• Overall Survival

  18 months

Study Arms (3)

MRD Negative

EXPERIMENTAL

All subjects will receive four cycles of durvalumab with SABR concurrent at cycle 2, then will be evaluated for MRD. Subjects in this arm have no detectable ctDNA at MRD landmark and will receive no further therapy.

Drug: Durvalumab; Radiation: Stereotactic Body Radiotherapy; Diagnostic Test: Circulating Tumor DNA assay

MRD Positive, no further therapy

EXPERIMENTAL

All subjects will receive four cycles of durvalumab with SABR concurrent at cycle 2, then will be evaluated for MRD. Subjects in this arm have detectable ctDNA at MRD landmark and are randomized to no further therapy.

Drug: Durvalumab; Radiation: Stereotactic Body Radiotherapy; Diagnostic Test: Circulating Tumor DNA assay

MRD Positive, consolidation durvalumab

EXPERIMENTAL

All subjects will receive four cycles of durvalumab with SABR concurrent at cycle 2, then will be evaluated for MRD. Subjects in this arm have detectable ctDNA at MRD landmark and are randomized to eight additional cycles of durvalumab

Drug: Durvalumab; Radiation: Stereotactic Body Radiotherapy; Diagnostic Test: Circulating Tumor DNA assay

Interventions

Durvalumab DRUG

Subjects will receive durvalumab 1500mg IV every four weeks for four cycles, undergo assessment for residual disease, then a subset of subjects will receive an additional eight cycles of durvalumab.

Also known as: MEDI4736, Imfinzi

MRD Negative; MRD Positive, consolidation durvalumab; MRD Positive, no further therapy

Stereotactic Body Radiotherapy RADIATION

Subjects will receive stereotactic radiation therapy concurrent with cycle 2 of durvalumab to a dose of 48Gy in four fractions. Fractionation may be modified for central tumors.

Also known as: Stereotactic Radiation, Stereotactic Radiation Therapy

MRD Negative; MRD Positive, consolidation durvalumab; MRD Positive, no further therapy

Circulating Tumor DNA assay DIAGNOSTIC_TEST

After four cycles of durvalumab, subjects will be evaluated at the MRD Landmark for residual ctDNA to determine subsequent treatment assignment.

Also known as: AVENIO ctDNA surveillance assay, MRD Landmark assay

MRD Negative; MRD Positive, consolidation durvalumab; MRD Positive, no further therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be competent, \>18yo at time of study entry, and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Patients with histological diagnosis of NSCLC, all histological sub-types are eligible
• Body weight \>30kg
• ECOG Performance status (PS) 0-2.
• Tumor stage T1-2 (≤5cm) N0 M0 (8th Edition of the TNM Classification for Lung Cancer) based on CT chest/abdomen, FDG-PET within 12 weeks of enrolment, and, where performed, EBUS-guided biopsy of hilar or mediastinal nodes within 8 weeks of enrolment.
• Subject deemed medically inoperable, or subject deemed operable but declines surgery following surgical assessment.
• Peripheral (outside a 2cm radius proximal bronchial tree) and central (within 2cm, but neither abuts nor invades proximal bronchial tree) tumors permitted.
• Screening laboratory values for organ function must meet the following criteria within 14 days prior to cycle 1 day 1:
• Bone Marrow: Absolute neutrophils ≥ 1.5 x 10\^9/L; Platelets ≥ 100 x 10\^9/L; Hemoglobin ≥ 90 g/L
• Kidney: Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age)
• ÷ 72 x serum creatinine (mg/dL)
• Females:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85

You may not qualify if:

• Any patient with malignancy which cannot be reliably defined on the treatment planning CT scan due to adjacent opacification from effusion, consolidation, or atelectasis.
• History of allogenic organ transplantation.
• History of active primary immunodeficiency
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C and HIV. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease

Sponsors & Collaborators

• University of British Columbia: lead
• AstraZeneca: collaborator
• Ozmosis Research Inc.: collaborator

Study Sites (5)

BC Cancer--Kelowna

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BC Cancer--Surrey

Surrey, British Columbia, V3V 1Z2, Canada

Location

BC Cancer--Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BC Cancer--Victoria

Victoria, British Columbia, V8R 6V5, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Adenocarcinoma of Lung; Neoplasm, Residual

Interventions

durvalumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Islam Mohamed, MD

  BC Cancer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: Study subjects will be analyzed as a single cohort with respect to the primary outcome, with comparison to historical controls. Treatment assignment based on biomarker status after initial treatment.

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: June 29, 2021
• Study Start: August 11, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)