Genomically Guided Radiation Dose Personalization in Locally Advanced NSCLC

NCT05873439 | Completed Early Phase 1 DMC

• 1 other identifier: MCC 21525
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Nonsmall Cell Lung Cancer; Nonsmall Cell Lung Cancer, Stage II; Nonsmall Cell Lung Cancer Stage III; Unresectable Non-Small Cell Lung Carcinoma

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Freedom from local regional progression (FFLRP)

  At 2 years

• Overall Survival (OS)

  At 2 years

Study Arms (3)

Arm A: RSI predicts dose ≤ 60 Gy

EXPERIMENTAL

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)

Arm B: RSI predicts dose > 60 Gy

EXPERIMENTAL

Participants will receive treatment with RxRSI guided boost to the primary tumor up to 81Gy (2.7Gy/fraction).

Radiation: Genomically Guided Radiation Therapy (RT)

Arm C: unable to calculate RSI

EXPERIMENTAL

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)

Interventions

Genomically Guided Radiation Therapy (RT) RADIATION

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.

Arm A: RSI predicts dose ≤ 60 Gy; Arm B: RSI predicts dose > 60 Gy; Arm C: unable to calculate RSI

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trial Search

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas Dilling, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2023
• First Posted: May 24, 2023
• Study Start: May 25, 2023
• Primary Completion: November 29, 2023
• Study Completion: August 21, 2024
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)