NBTXR3 and Radiation Therapy for the Treatment of Inoperable Recurrent Non-small Cell Lung Cancer

NCT04505267 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: 2020-0123NCI-2020-04580P30CA016672
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial investigates the best dose and side effects of NBTXR3 when given together with radiation therapy for the treatment of non-small cell lung cancer that cannot be treated by surgery (inoperable) and has come back (recurrent). NBTXR3 is a radio-enhancer designed to increase the radiotherapy energy dose deposition inside tumor cells. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving NBTXR3 and radiation therapy may increase radiation-dependent tumor cell killing without increasing the radiation exposure of healthy surrounding tissues.

Conditions

Stage IA2 Lung Cancer AJCC v8; Stage IA3 Lung Cancer AJCC v8; Stage IB Lung Cancer AJCC v8; Stage IIA Lung Cancer AJCC v8; Stage IIB Lung Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Unresectable Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage I Lung Cancer AJCC v8; Stage IA1 Lung Cancer AJCC v8; Stage II Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (4)

• Incidence of dose limiting toxicity (DLT) Cohort 1

  Defined as the occurrence and frequency of DLTs by dose level of NBTXR3. Descriptive summary tables will be produced, providing the DLTs by initial planned dose level of NBTXR3, initial planned volume of NBTXR3 to be injected, the injected volume and the RT dose given.

  Day 1 to 3 months post radiation therapy (RT)

• Determination of the Recommended Phase II Dose (RP2D)

  Will be selected based on isotonic regression. Specifically, the recommended phase II dose (RP2D) will be determined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate (30%).

  4 weeks post RT

• Incidence of dose limiting toxicity (DLT) Cohort 2

  Defined as the occurrence and frequency of DLTs by dose level of hafnium oxide-containing nanoparticles NBTXR3 (NBTXR3). Descriptive summary tables will be produced, providing the DLTs by initial planned dose level of NBTXR3, initial planned volume of NBTXR3 to be injected, the injected volume and the RT dose given. Incidence of dose-limiting toxicities (DLTs) for NBTXR3 with RT. The DLT window for cohort 2 (NBTXR3 + RT) is from Day 1 to 4 weeks post RT.

  Day 1 to 4 weeks post RT

• Determination of the maximum tolerated dose (MTD)

  Determination of the MTD will be selected based on isotonic regression. Specifically, the MTD will be determined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate (30%).

  4 weeks post RT

Secondary Outcomes (9)

• Incidence of NBTXR3/RT related late onset toxicities

  Up to 5 years

• Feasibility of NBTXR3 injection in lung

  Up to 5 years

• Feasibility of the regional lymph nodes

  Up to 5 years

• Objective response rate (ORR)

  Up to 5 years

• Local disease control rate (LDCR)

  At 1 and 2 years

Other Outcomes (3)

• Tumor microenvironment

  Up to 5 years

• Immune activation

  Up to 5 years

• Circulating tumor deoxyribonucleic acid (DNA) mutations

  Up to 5 years

Study Arms (1)

Treatment (NBTXR3, RT)

EXPERIMENTAL

Patients receive NBTXR3 IT or intranodally on day 1. Within 15 days, patients undergo RT 5 times weekly (Monday-Friday) over 3 weeks for a total of 10-15 fractions.

Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Radiation: Radiation Therapy

Interventions

Hafnium Oxide-containing Nanoparticles NBTXR3 OTHER

Given IT or intranodally

Also known as: NBTXR3

Treatment (NBTXR3, RT)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (NBTXR3, RT)

Eligibility Criteria

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

You may qualify if:

• Biopsy proven locoregionally recurrent NSCLC after prior definitive radiation therapy, or patients that have imaging characteristics highly suggestive of recurrence but no pathologic or cytologic diagnosis. Pathologic diagnosis will be confirmed during the procedure to inject NBTXR3, prior to injecting the drug. If pathologic diagnosis cannot be established, the procedure will be aborted and the patient will be considered a screening failure. For stage IV patients, oligometastatic disease should be confirmed at screening. Oligometastatic disease is defined as ≤ 3 cancer lesions, not including the primary tumor.
• Participant deemed medically inoperable by the investigator or treating physician.
• Overlap between recurrent disease in need of treatment and prior radiation treatment field as determined by treating Radiation Oncologist.
• As a general reference, recurrent disease within 50% isodose line of prior radiation treatment field would be considered significant.
• Radiation treatment received more than 6 months prior to enrollment.
• Amenable to undergo bronchoscopic (EBUS, CBCT) or CT-guided injection of NBTXR3 as per investigator or treating physician.
• Up to 4 lung lesions may be injected with NBTXR3, including the primary tumor, involved lymph node(s), and/or metastatic lesion(s).
• At least 1 injected lesion should be located within a reirradiation field.
• All injected lesions must be radiated.
• The target lesion(s) should be measurable on cross sectional imaging (RECIST 1.1).
• a. Nodal target lesions must be ≥15 mm (short axis) based on CT (slice thickness of 5 mm or less) or MRI.
• Age ≥ 18 years
• ECOG Performance Status 0-2
• For cohort 1, adequate laboratory values to receive radiation as determined by the principal investigator or treating physician.
• For cohort 2 laboratory values at screening:

You may not qualify if:

• At screening, past medical history of:
• Interstitial lung disease, excluding drug-induced ILD, speficially immunotherapy-induced pneumonitis that has been resolved
• Any Grade 4 thoracic radiation related toxicity
• Unresolved radiation related
• i. Esophagitis ii. Pneumonitis iii. Bronchopulmonary hemorrhage d. Any Grade i. Esophageal perforation ii. Radiation associated airway necrosis iii. Bronchoesophageal fistula e. Any Grade i. Esophageal perforation ii. Radiation associated airway necrosis iii. Bronchoesophageal fistula iv. Tracheoesophageal fistula v. Spinal cord myelopathy
• Has received any approved or investigational anti-neoplastic or immunotherapy agent within 2 weeks prior to NBTXR3 injection
• Use of concurrent systemic therapy (chemotherapy, immunotherapy, targeted therapy) or patient participation on another therapeutic clinical trial.
• Active malignancy, in addition to locoregionally recurrent NSCLC, with the exception of definitively treated and relapse free within 1 year from diagnosis of non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively treated and relapse free with at least 2 years elapsed since the diagnosis of the other primary malignancy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment.
• Known active, uncontrolled (high viral load) HIV or hepatitis B or hepatitis C infection
• Female patients who are pregnant or breastfeeding.
• Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period. Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of \< 1% per year when used consistently and correctly.
• Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Cognitively impaired subjects

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Saumil Gandhi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: August 10, 2020
• Study Start: February 10, 2021
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)