Clinical Trials /

NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy

NCT03589339

Description:

The 1100 study is an open-label, Phase I, prospective clinical study to assess the safety of intratumoral injection of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: NBTXR3 Activated by SABR for Patients With Advanced HNSCC or NSCLC Treated With an Anti-PD1 Antibody
  • Official Title: A Phase I/II Study of NBTXR3 Activated by SABR for Patients With Advanced HNSCC or NSCLC Treated With an Anti-PD1 Antibody

Clinical Trial IDs

  • ORG STUDY ID: NBTXR3-1100
  • NCT ID: NCT03589339

Conditions

  • Head and Neck Cancer
  • NSCLC
  • Radiotherapy
  • Immunotherapy

Interventions

DrugSynonymsArms
NBTXR3NBTXR3 activated by SABR

Purpose

The study is an open label Phase I/II prospective clinical trial, non randomized, which consists of two consecutive steps, a dose escalation and a subsequent dose expansion part. The phase I and II parts include different patient population.

Detailed Description

      Escalation dose part:

      Elegible patients will receive a single intratumoral injection of NBTXR3 concurrently with an
      approved anti-PD1 and will receive external beam radiotherapy starting 24 hours after the
      injection up to completion of 15 days of treatment.

      Expansion dose part:

      Elegible patients will receive a single intratumoral injection of NBTXR3 concurrently with an
      approved anti-PD1 and will receive external beam radiotherapy starting 24 hours after the
      injection up to completion of 15 days of treatment at recommended NBTXR3 dose and recommended
      radiotherapy dose.

      A visit of end of treatment will take place approximately 3-4 weeks after last radiotherapy
      fraction. Patients will be followed for evaluation of their disease status and adverse event
      until the end of the study.
    

Trial Arms

NameTypeDescriptionInterventions
NBTXR3 activated by SABRExperimental
  • NBTXR3

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18

          -  Histologically-proven inoperable loco- regional recurrent HNSCC with tumor in
             previously irradiated Head Neck field which is amenable to re-irradiation with SABR

          -  Histologically-proven recurrent AND metastatic HNSCC with tumor in previously
             irradiated Head Neck field which is amenable to re-irradiation with SABR

          -  Histologically-proven lung metastasis, accessible to intratumoral injection, not
             previously irradiated, from HNSCC not amenable to re-irradiation if synchronous
             locoregional recurrence and metastasis, or from NSCLC (squamous and non squamous
             types),

          -  Histologically-proven liver metastasis, accessible to intratumoral injection, not
             previously irradiated, from HNSCC not amenable to re-irradiation if synchronous
             locoregional recurrence and metastasis, or from NSCLC (squamous and non squamous
             types),

          -  Known status of human papillomavirus infection, in patients with oropharyngeal SCC

          -  HNSCC with prior irradiation, concurrent or not with platin-based chemotherapy or
             cetuximab

          -  Non symptomatic CNS metastasis is elegible

          -  NSCLC previously treated or not with a platinum based-regimen

          -  Patients with NSCLC tumors with EGFR or ALK genomic aberrations must have had disease
             progression under approved molecular targeted therapy

          -  Metastatic patients must have received an approved anti-PD1 with SD for at least for
             12 weeks or with confirmed PD at 12 weeks

          -  Karnofsky performance status ≥60

          -  Life expectancy >12 weeks

          -  Adequate function of bone marrow

          -  Adequate liver function

          -  Adequate kidney function:

          -  Non-childbearing potential:

               -  All female patients of childbearing potential must have a negative serum
                  pregnancy test within the 7 days prior to NBTXR3 administration.

               -  Female patients of childbearing potential must agree and use at least 2 forms of
                  highly effective methods of contraception, including at least 1 barrier method
                  starting with the first dose of study therapy through 150 days after the last
                  dose of study therapy.

               -  Male patients and their sexual partner(s) of childbearing potential must agree
                  and use at least 2 forms of highly effective methods of contraception, including
                  at least 1barrier method starting with the first dose of study therapy through
                  150 days after the last dose of study therapy.

        Exclusion Criteria:

          -  Written Informed Consent not obtained, signed and dated

          -  Hypersensitivity to anti-PD1 monoclonal antibody

          -  History of severe immune-related adverse event requiring treatment discontinuation

          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy in excess of
             physiologic dose within 7 days prior to treatment start

          -  Active autoimmune disease requiring systemic treatment in the past year

          -  History of non-infectious pneumonitis or HIV

          -  Active hepatitis B or hepatitis C

          -  Peripheral neuropathy >grade 2

          -  Loco-regional recurrent HNSCC with ulceration

          -  Target lung metastatic lesion <2 cm

          -  Metastatic lesion not easily accessible for intratumoral/intralesional injection.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             severe infection, symptomatic congestive heartfailure, acute coronary syndrome, etc.

          -  Medical history of life-threatening ventricular arrhythmia

          -  Concurrent treatment with any other anticancer therapy not determined by the study
             treatment or planning to receive these treatments during the study

          -  Patients unable to comply with scheduled visits, treatment plans, laboratory tests,
             and other study procedures or those with severe psychiatric illness/social situations
             that would limit compliance with study requirements

          -  Patients participating in another clinical investigation at the time of signature of
             the informed consent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase1: Determination of the Maximum Tolerated Doses and the early Dose Limitting Toxicities (DLT)
Time Frame:24 months
Safety Issue:
Description:To determine the Maximum Tolerated Dose/s and the early Dose Limiting Toxicities (DLT) of intratumoral/intralesional injection of NBTXR3 activated by SABR in combination with an anti-PD1 antibody,

Secondary Outcome Measures

Measure:Phase1: Incidence of clinical and laboratory adverse events and serious adverse events
Time Frame:24 months
Safety Issue:
Description:To assess the incidence of clinical and laboratory adverse events and serious adverse events.
Measure:Phase1: Late onset grade ≥ 3 NCI CTCAE adverse events
Time Frame:24 months
Safety Issue:
Description:To determine the late onset toxicity of NBTXR3 given as intratumoral/intralesional injection activated by SABR in combination with an anti-PD1 antibody. To assess the "late onset" grade ≥ 3 NCI CTCAE adverse events.
Measure:Phase2: Body Kinetic characterization by quantification of Hafnium in whole blood and urine.
Time Frame:24 months
Safety Issue:
Description:To characterize the body kinetic profile by quantification of Hafnium at day 1 of NBTXR3 intratumoral/intralesional injection, activated by SABR in combination with an anti-PD1 antibody.Whole blood will be collected at the end of injection up to 4 hours post end injection. Urine sample will be collected twice after injection.
Measure:Phase2: Tumor response assessment by RECIST version 1.1 and iRECIST criteria
Time Frame:24 months
Safety Issue:
Description:To assess tumor response by RECIST version 1.1 and iRECIST criteria

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Nanobiotix

Last Updated

July 4, 2018