NBTXR3 and Radiation Therapy for the Treatment of Inoperable Recurrent Non-small Cell Lung Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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Phase 1 |
Detailed Description
PRIMARY OBJECTIVE:
- To determine the recommended phase II dose (RP2D) of hafnium oxide-containing nanoparticles NBTXR3 (NBTXR3) activated by radiotherapy in patients with inoperable, locoregional recurrent non-small cell lung cancer (NSCLC), previously treated with definitive radiation therapy.
SECONDARY OBJECTIVES:
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To evaluate the safety and feasibility of reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC.
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To evaluate the anti-tumor response of reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC.
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To evaluate time-to-event outcomes after reirradiation with NBTXR3 in patients with inoperable, locoregionally recurrent NSCLC
EXPLORATORY OBJECTIVE:
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (NBTXR3, RT) 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
Given IT or intranodally
Other Names:
Radiation: Radiation Therapy
Undergo RT
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of dose limiting toxicity (DLT) Cohort 1 [Day 1 to 3 months post radiation therapy (RT)]
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.
- Determination of the Recommended Phase II Dose (RP2D) [4 weeks post RT]
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%).
- Incidence of dose limiting toxicity (DLT) Cohort 2 [Day 1 to 4 weeks post RT]
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.
- Determination of the maximum tolerated dose (MTD) [4 weeks post RT]
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%).
Secondary Outcome Measures
- Incidence of NBTXR3/RT related late onset toxicities [Up to 5 years]
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.
- Feasibility of NBTXR3 injection in lung [Up to 5 years]
Feasibility is defined as the ability to do intratumoral and/or intranodal lung injection of NBTXR3.
- Feasibility of the regional lymph nodes [Up to 5 years]
Feasibility is defined as the ability to do intratumoral and/or intranodal lung injection of NBTXR3.
- Objective response rate (ORR) [Up to 5 years]
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.
- Local disease control rate (LDCR) [At 1 and 2 years]
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.
- Local progression free survival (LPFS) [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]
Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.
- Distant progression free survival (DPFS) [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]
Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.
- Progression free survival (PFS) [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]
Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.
- Overall survival (OS) [From NBTXR3 injection to death from any cause or EoS, assessed up to 5 years]
Will be estimated by the Kaplan-Meier method. Median times and 95% confidence intervals will also be estimated.
Other Outcome Measures
- Tumor microenvironment [Up to 5 years]
Analyzed using multiplexed immunohistochemistry.
- Immune activation [Up to 5 years]
Will be quantified by flow cytometry analysis of T and B cells, peripheral blood mononuclear cells.
- Circulating tumor deoxyribonucleic acid (DNA) mutations [Up to 5 years]
Will assess the concordance of circulating tumor DNA mutations to those detected in non-small cell lung cancer (NSCLC) tumor-derived DNA.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Biopsy proven locoregional recurrent NSCLC after prior definitive radiation therapy
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Participant is deemed medically inoperable by the investigator or treating physician
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Overlap between recurrent disease in need of treatment and prior radiation treatment field as determined by treating radiation oncologist
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As a general reference, recurrent disease within 50% isodose line of prior radiation treatment field would be considered significant
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Radiation treatment received more than 6 months prior to enrollment
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Amenable to undergo bronchoscopic (endobronchial ultrasound [EBUS], cone-beam computed tomography [CBCT]) or computed tomography (CT)-guided injection of NBTXR3 as per investigator or treating physician
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The target lesion(s) should be measurable on cross sectional imaging (Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 and immune-related [ir]RECIST),
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Up to 4 target lesions may be injected and reirradiated, including the primary tumor and involved lymph node(s)
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Nodal target lesions must be >= 15 mm (short axis) based on CT (slice thickness of 5 mm or less) or magnetic resonance imaging (MRI)
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Eastern Cooperative Oncology Group (ECOG) performance status 0-2
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Hemoglobin >= 8.0 g/dL
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Absolute neutrophil count (ANC) >= 1,500/mm^3
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Platelet count >= 100,000/mm^3
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Creatinine =< 1.5 x upper limit of normal (ULN)
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Calculated (Calc.) creatinine clearance > 45 mL/min
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Total bilirubin =< 2.0 mg/dL
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Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
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Negative urine or serum pregnancy test =< 7 days of NBTXR3 injection in all female participants of child-bearing potential
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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
Exclusion Criteria:
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NSCLC with radiographic evidence of distant metastases at screening
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At screening, past medical history of:
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Interstitial lung disease
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Drug related pneumonitis
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Any grade 4 thoracic radiation related toxicity
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Unresolved radiation related
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Esophagitis
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Pneumonitis
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Bronchopulmonary hemorrhage
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Any grade
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Esophageal perforation
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Radiation associated airway necrosis
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Bronchoesophageal fistula
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Tracheoesophageal fistula
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Spinal cord myelopathy
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Has received any approved or investigational anti-neoplastic or immunotherapy agent within 4 weeks prior to NBTXR3 injection
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Note: a reduced washout window may be considered for therapies with short half-lives (e.g., kinase inhibitors) after discussion with Nanobiotix, investigational new drug (IND) medical monitor and investigator
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Use of concurrent systemic therapy (chemotherapy, immunotherapy, targeted therapy) or patient participation on another therapeutic clinical trial
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Known contraindication to iodine-based or gadolinium-based intravenous (IV) contrast
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Active malignancy, in addition to locoregional 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 definitely treated and relapse free with at least 2 years elapsed since the diagnosis of the other primary malignancy
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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
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Known active, uncontrolled (high viral load) human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
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Female patients who are pregnant or breastfeeding
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Saumil Gandhi, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2020-0123
- NCI-2020-04580
- 2020-0123
- P30CA016672