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Recurrent Lung Non-Small Cell CarcinomaPhase 1NCT04505267

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

A Phase 1 study testing Hafnium Oxide-containing Nanoparticles NBTXR3 and Radiation Therapy in people with Recurrent Lung Non-Small Cell Carcinoma and Stage I Lung Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hafnium Oxide-containing Nanoparticles NBTXR3 and Radiation Therapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
10 Feb 2021to 31 Mar 2028
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • 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:
  • Hemoglobin ≥ 8.0 g/dL
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
  • Platelet Count ≥ 100,000/mm3
  • Creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Calc. Creatinine Clearance ≥ 30 mL/min
  • Total Bilirubin ≤ 2.0 mg/dL
  • AST / ALT ≤ 3.0 x upper limit of normal (ULN) or 5.0 x ULN if known liver metastases
  • Serum albumin ≥ 3.0 g/dL
  • Negative urine or serum pregnancy test ≤ 7 days of NBTXR3 injection in all female of child-bearing potential.
  • Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
  • English speaking or Non-English Speaking subjects

Who cannot join

  • 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
  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Study of Reirradiation With NBTXR3 for Inoperable Locoregional Recurrent Non-Small Cell Lung Cancer (NSCLC)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the safety of 45 Gy in 15 fractions in patients with inoperable, locoregional recurrent NSCLC, previously treated with definitive radiation therapy.

II. To determine the recommended phase II dose (RP2D) of NBTXR3 activated by radiotherapy in patients with inoperable, locoregional recurrent NSCLC, previously treated with definitive radiation therapy.

SECONDARY OBJECTIVES:

  1. To evaluate the safety and feasibility of reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC.

II. To evaluate the anti-tumor response of reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC.

III. To evaluate time-to-event outcomes after reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC

EXPLORATORY OBJECTIVE:

  1. To assess biomarkers of response in patients treated with NBTXR3/radiation therapy (RT).

OUTLINE: This is a dose-escalation and dose-expansion study of NBTXR3.

Patients receive NBTXR3 intratumorally (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.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for up to 5 years.

Being tested
Hafnium Oxide-containing Nanoparticles NBTXR3, Radiation Therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hafnium Oxide-containing Nanoparticles NBTXR3Other

    Also called NBTXR3

    Given IT or intranodally

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated

    Undergo RT

Study groups in NCT04505267
Study groupRoleWhat they receive
Treatment (NBTXR3, RT)ExperimentalPatients 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.
Receives: Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 1 to 3 months post radiation therapy (RT)

  2. 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%).

    Measured: 4 weeks post RT

  3. 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.

    Measured: Day 1 to 4 weeks post RT

  4. 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%).

    Measured: 4 weeks post RT

Secondary outcomes (9)

  1. Incidence of NBTXR3/RT related late onset toxicities

    Defined as any grade >= 3 adverse events (AE) occurring after the end of treatment visit and until end of study (EoS). All AEs will be coded and graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events version (v)5 criteria.

    Measured: Up to 5 years

  2. Feasibility of NBTXR3 injection in lung

    Feasibility is defined as the ability to do intratumoral and/or intranodal lung injection of NBTXR3.

    Measured: Up to 5 years

  3. Feasibility of the regional lymph nodes

    Feasibility is defined as the ability to do intratumoral and/or intranodal lung injection of NBTXR3.

    Measured: Up to 5 years

  4. Objective response rate (ORR)

    Defined as the proportion of participants with either a complete response (CR) or a partial response (PR) (ORR=CR + PR) or stable disease (SD) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune-related (ir)RECIST in the target lesion(s) and overall.

    Measured: Up to 5 years

  5. Local disease control rate (LDCR)

    Defined as the proportion of patients who demonstrate a radiographic response to treatment (RECIST v1.1 and irRECIST). The response to treatment should be a CR, PR and/or SD within the selected target lesion(s). Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.

    Measured: At 1 and 2 years

  6. Local progression free survival (LPFS)

    Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.

    Measured: From NBTXR3 injection to local (i.e., within the lungs or regional nodes) disease recurrence, local progression, or death from any cause, assessed up to 5 years

  7. Distant progression free survival (DPFS)

    Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.

    Measured: From NBTXR3 injection to the radiographic confirmation (RECIST v1.1 and irRECIST) of a new lesion outside the lungs and regional nodes or death from any cause, assessed up to 5 years

  8. Progression free survival (PFS)

    Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.

    Measured: From NBTXR3 injection to local or recurrence, local progression, distant progression, confirmed radiographically (RECIST v1.1 and irRECIST), or death from any cause, assessed up to 5 years

  9. Overall survival (OS)

    Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.

    Measured: From NBTXR3 injection to death from any cause or EoS, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2020
  2. Study start10 Feb 2021
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04505267
Sponsor's protocol ID
2020-0123
Other IDs
NCI-2020-04580, 2020-0123, P30CA016672
Status last verified
Aug 2026
First submitted
14 Jul 2020
Last updated
19 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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