Treatment of Pulmonary SUlcus, Pancoast and Chest Wall Non-small Cell Lung Cancer Employing Radiation, Immuno-oncology and Resection

NCT06331455 | Recruiting Phase 2 DMC

• 1 other identifier: 23-5501
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The SUPER trial is a prospective Phase II trial. It is designed for patients with stage 2 or 3 non-small cell lung cancer (NSCLC) prior to surgery. Patients who are enrolled in this trial will receive combination of Non-ablative oligofractionated radiation (NORT) and two cycles of Durvalumab, an immunotherapy drug before their surgery.

Conditions

Lung Cancer Patients; Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• To Measure CD8 TILs density & Major Pathological Response (MPR)

  1. The proportion of patients achieving MPR after neoadjuvant therapy 2. The proportion of patients doubling the CD8 TILs density after neoadjuvant therapy.

  5-6 weeks post treatment

Secondary Outcomes (1)

• To explore the efficacy and safety of NORT-durvalumab

  12 weeks post surgery

Study Arms (1)

Neoadjuvant NORT-Durvalumab

EXPERIMENTAL

administration of non-ablative oligofractionated radiation therapy using 12 Gy in 3 fractions in combination with two doses of durvalumab (1500 mg IV) prior to surgery.

Drug: Durvalumab; Radiation: Non-ablative oligofractionated radiation (NORT)

Interventions

Durvalumab DRUG

Two doses of durvalumab (1500 mg IV)

Neoadjuvant NORT-Durvalumab

Non-ablative oligofractionated radiation (NORT) RADIATION

12 Gy of Radiation in 3 fractions

Neoadjuvant NORT-Durvalumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Body weight \>30 kg
• Adequate normal organ and marrow function as defined below Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.0 × 10\^9/L Platelet count ≥75 × 10\^9/L Serum bilirubin in normal range with the exception of Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
• 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 / 72 x serum creatinine (mg/dL)
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks
• Tumor amenable to biopsy
• Patients with NSCLC stage IIB to IIIB.
• PD-L1 positive tumors defined by tumor proportion score (TPS) \>1%

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 8 weeks before enrollment
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Known oncogenic driver mutations such as EGFR mutant or ALK mutant
• The presence of N3 disease in the contralateral mediastinum, contralateral hilum, or contralateral supraclavicular lymph node confirmed histologically.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the StudySponsor.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• History of allogenic organ transplantation.
• 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 Sponsor Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
• History of another primary malignancy except for:
• Malignancy treated with curative intent that does not require treatment, nor anticipated to require treatment for the duration of the study, and in the opinion of the investigator would not pose a risk of increased toxicity, or difficulty to follow the protocol and assess study endpoints Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis, malignant pleural effusion or distant metastasis (M1)
• Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry

Sponsors & Collaborators

• Marc de Perrot: lead
• Ozmosis Research Inc.: collaborator

Study Sites (1)

Toronto General Hospital

Toronto, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Marc de Perrot, MD, FRCSC

  UHN - Toronto General Hopsital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc de Perrot, MD, FRCSC

CONTACT

4163405549; marc.deperrot@uhn.ca

Fatemeh Zaeimi, MSc

CONTACT

4163405686; fatemeh.zaeimi@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Thoracic Surgeon

Model Details: This is a multi-centre, phase 2 trial in patients with T2b-3N0-1M0 NSCLC evaluating the biologic efficacy of NORT-Durvalumab administered prior to surgery.

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: March 26, 2024
• Study Start: May 22, 2024
• Primary Completion: December 1, 2025
• Study Completion: April 1, 2026
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)