Genomically Guided Radiation Dose Personalization in Locally Advanced NSCLC

A Feasibility Study of Genomically Guided Radiation Dose Personalization in the Management of Locally Advanced Non-Small Cell Lung Cancer

The purpose of the study is to determine the feasibility of genomically guided radiation therapy (RT) with concurrent chemotherapy in the management of stage II and III non-small cell lung cancer (NSCLC).

Study Overview

• Status: Recruiting
• Conditions: Nonsmall Cell Lung Cancer; Nonsmall Cell Lung Cancer Stage III; Unresectable Non-Small Cell Lung Carcinoma; Nonsmall Cell Lung Cancer, Stage II
• Intervention / Treatment: Radiation: Genomically Guided Radiation Therapy (RT)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Thomas Dilliing, MD; Phone Number: 813-745-8424; Email: Thomas.Dilling@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Amalin Asous; Phone Number: 813-745-6470; Email: Amalin.Asous@moffitt.org
      • Principal Investigator: Thomas Dilling, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of AJCC Stage 2 or Stage 3 unresectable NSCLC as determined by a multidisciplinary oncology team
• Confirmation of NSCLC with availability of fresh tumor biopsy by tissue biopsy which can include adenocarcinoma, squamous cell, large cell carcinoma, or NSCLC not otherwise specified
• Life expectancy >12 weeks
• Normal renal (creatinine <1.5 × upper limit of normal [ULN]), liver (bilirubin < 1.5 × ULN, transaminases <3.0 × ULN, except in known hepatic disease, wherein may be <5 × ULN) and blood counts (white blood cells ≥2.5, neutrophils ≥1000, platelets ≥50, 000, hemoglobin ≥8)
• ECOG 0-1
• Age ≥ 18 years
• Participants with surgery within 14 days should have recovered from all effects of the surgery and be cleared by their surgeon
• There is no limit on prior systemic or therapies
• Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
• Ability to sign an informed consent form, which can be signed by a family member or health care proxy. Informed consent must be given before any study related procedures occur.

Exclusion Criteria:

• Current or prior participation in a study of an investigational agent or investigational device within 2 weeks of the first dose of study treatment
• Major surgery or significant traumatic injury that has not been recovered from 14 days before the initiation of study drug
• Women who are pregnant or breastfeeding
• History of allergy or hypersensitivity to any of the study drugs or study drug components
• Concurrent brain metastases or leptomeningeal disease
• History of prior malignancy within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of > 90%), such as but not limited to, non-melanoma skin carcinoma, ductal carcinoma in situ, or stage I endometriod uterine cancer, and others at the discretion of the PI
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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 (eg, 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 Principal Investigator
• • Patients with celiac disease controlled by diet alone
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
• • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
• • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: RSI predicts dose ≤ 60 Gy; Participants will receive standard RT dose of 60Gy in 30 fractions targeting the primary tumor and any involved regional lymph nodes.	Radiation: Genomically Guided Radiation Therapy (RT); Based on the Radiosensitivity Index (RSI) from testing participants tumor sample, participants will receive either standard dose radiation therapy, which is a strength 60Gy or up to 81Gy strength. Radiation treatment is administered 5 days per week for approximately 6 weeks.
Experimental: Arm B: RSI predicts dose > 60 Gy; Participants will receive treatment with RxRSI guided boost to the primary tumor up to 81Gy (2.7Gy/fraction).	Radiation: Genomically Guided Radiation Therapy (RT); Based on the Radiosensitivity Index (RSI) from testing participants tumor sample, participants will receive either standard dose radiation therapy, which is a strength 60Gy or up to 81Gy strength. Radiation treatment is administered 5 days per week for approximately 6 weeks.
Experimental: Arm C: unable to calculate RSI; Participants in will receive standard RT dose of 60Gy in 30 fractions targeting the primary tumor and any involved regional lymph nodes.	Radiation: Genomically Guided Radiation Therapy (RT); Based on the Radiosensitivity Index (RSI) from testing participants tumor sample, participants will receive either standard dose radiation therapy, which is a strength 60Gy or up to 81Gy strength. Radiation treatment is administered 5 days per week for approximately 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Unacceptable Toxicity	Rate of Unacceptable Toxicity will be measured during 12 week period following study enrollment. Unacceptable toxicity is defined as any grade 4 or 5 adverse event (AE) probably or definitely related to experimental dose escalated radiation therapy	12 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from local regional progression (FFLRP)	Freedom from local regional progression (FFLRP) will be defined as lack of progression as documented by response assessment imaging following completion of concurrent chemotherapy and radiation.	At 2 years
Overall Survival (OS)	Overall Survival (OS) will be measured from the date of first treatment to the date of death due to any cause.	At 2 years

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Thomas Dilling, MD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trial Search

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: MCC 21525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes