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NBTXR3 Crystalline Nanoparticles and Stereotactic Body Radiation Therapy in the Treatment of Liver Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02721056
Recruitment Status : Unknown
Verified October 2016 by Nanobiotix.
Recruitment status was:  Recruiting
First Posted : March 28, 2016
Last Update Posted : February 3, 2017
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Nanobiotix

Tracking Information
First Submitted Date  ICMJE December 24, 2015
First Posted Date  ICMJE March 28, 2016
Last Update Posted Date February 3, 2017
Study Start Date  ICMJE November 2015
Estimated Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Determination of the Recommended Doses Toxicities (DLT) [ Time Frame: 20 Months ]
    To determine the Recommended Doses (DLT) of NBTXR3 administered as two different schedules (intra-lesional or intra-arterial injection), activated by Stereotactic Body Radiation Therapy (SBRT)
  • Determination of the early Dose Limiting [ Time Frame: 20 Months ]
    To determine the early Dose Limiting Toxicities
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Number of patients with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 20 Months ]
  • Response Rate [ Time Frame: 20 Months ]
  • Local Progression Free Survival [ Time Frame: 20 Months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NBTXR3 Crystalline Nanoparticles and Stereotactic Body Radiation Therapy in the Treatment of Liver Cancers
Official Title  ICMJE A Phase I-II Study of NBTXR3 Activated by Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Liver Cancers
Brief Summary The purpose of this Phase I / II study is to evaluate the safety and preliminary efficacy of NBTXR3 nanoparticles given by intralesional (IL) or intraarterial (IA) injection and activated by Stereotactic Body Radiation Therapy in the treatment of liver cancers.
Detailed Description

This is a prospective, open-label, non-comparative and non-randomized study, to be conducted in 2 phases:

  • a dose-escalation phase, to determine the recommended dose of NBTXR3 and to evaluate its safety/tolerability and preliminary clinical activity; and
  • a dose-expansion phase, which will be a cohort expansion at the recommended dose of NBTXR3.

Patients will receive a single administration of NBTXR3 on day of injection, as a super selective transcatheter arterial or intrahepatic lesion injection activated by Stereotactic Body Radiation Therapy starting 24 hours post injection. The total radiotherapy dose will be maximum 45 Gy, delivered as three fractions of 15 Gy each max, over 5 to 7 days (45 Gy, 3x15 Gy, over 5 to 7 days).

the visit of End of Treatment (EOT) will take place 12 to 13 weeks after the administration of the last radiotherapy fraction and includes the evaluation of global clinical, radiological and laboratory parameters.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatocellular Carcinoma
  • Liver Cancer
Intervention  ICMJE Radiation: NBTXR3, IL or IA injection + SBRT
Patients will receive a single administration of NBTXR3 on day of injection, as intralesional or super selective transcatheter arterial injection activated by Stereotactic Body Radiation Therapy starting 24 hours post injection. The total radiotherapy dose will be maximum 45 Gy, delivered as three fractions of 15 Gy each max, over 5 to 7 days (45 Gy, 3x15 Gy, over 5 to 7 days).
Study Arms  ICMJE Experimental: NBTXR3, IL or IA injection +SBRT
  • Patients will receive a single intralesional (IL) injection of NBTXR3 at four increasing dose levels (Volume levels) equivalent to: 10%, 15%, 22%, and 33% of the baseline tumor volume, activated by SBRT.
  • Patients with primary and secondary nodular intra hepatic cancers only will receive a single superselective transcatheter arterial (IA) injection of NBTXR3 at five increasing dose levels (Volume levels) equivalent to: 10%, 15%, 22%, 33% and 45% of the baseline tumor volume, activated by SBRT.
Intervention: Radiation: NBTXR3, IL or IA injection + SBRT
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: March 22, 2016)
200
Original Actual Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18
  • Written Informed Consent obtained, signed and dated
  • Eastern Cooperative Oncology Group performance status 0 or 1
  • Life expectancy > 6 months
  • Liver metastases from other primary cancers 1) with histologic confirmation of metastases, or 2) histologic confirmation of primary cancer and multiple new enhancing lesions in the liver consistent with metastases, or 3) histologic confirmation of primary cancer and a growing enhancing lesion in the liver consistent with a metastasis
  • Unresectable tumor/s, based on the opinion of an experienced surgeon specializing in hepatic resection, or the patient must be medically inoperable
  • Patients with extra-hepatic metastases controlled by supportive care or concomitant hormonotherapy are eligible.
  • Previous liver resection or local treatment (radiofrequency ablative therapy, chemoembolization, microwave treatment…) is permitted
  • Patients must have recovered from the effects of previous therapy (residual AE grade 0 or 1)
  • At least one tumor lesion that can be accurately measured in at least one dimension according to RECIST 1.1
  • Normal permeability of hepatic artery evaluated by injected CT-scan (arterial phase)
  • 700 cc of liver volume without tumor involvement and a radiation therapy dose < 15 Gy
  • Female patients must have a negative serum/urinary pregnancy test

The following laboratory parameters:

  • Platelet count ≥ 50 x 10^9/L
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutrophil count ≥ 1.5 x 10^9/L,
  • Prothrombin Ratio > 50%
  • Prothrombin time - International Normalized Ratio (INR) < 1.5 or correctable with vitamin K
  • Patients receiving anti-coagulation or anti-aggregant therapy must stop temporarily during treatment.
  • Total bilirubin <30 μmol/l
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal
  • Albumin >2.5 g/dL
  • Very low or undetectable Hepatitis B Virus DNA and Hepatitis C Virus RNA
  • Serum Creatinine ≤ 1.5 time the upper limit of normal value
  • Glomerular Filtration Rate > 44 mL/min/1.73m2
  • Pa O2 > 85 mm Hg

Exclusion Criteria:

  • Patients with ongoing chronic active viral B or C hepatitis must have received an antiviral treatment with negativation of the viremia or very low viremia before the onset of the radiation therapy
  • Biliary tract dilatation, biliodigestive anastomosis, bile duct drainage
  • Uncontrolled extra-hepatic metastatic disease with a symptomatic treatment or well tolerated hormonotherapy (AE 0/1)
  • Previous cancer cured for less than 2 years
  • Previous anticancer treatment (chemotherapy or/and biologicals) with a wash out < 4 weeks
  • Previous treatment with intra-arterial injection of Y90 loaded microspheres
  • Previous intra-arterial chemotherapy
  • Prior radiation therapy to the right upper abdomen, precluding reirradiation of the liver. That is, any previous radiation therapy in which a mean dose to the liver of 15 Gy in conventional fractionation was delivered, or previous doses to critical normal structures that would make re-irradiation unsafe
  • Impossibility to follow the dosimetry constraints (mean total liver dose > 15Gy)
  • Presence of arterio-veinous intra tumoral shunting
  • Encephalopathy related to liver failure
  • Clinical ascitis
  • Previous or concurrent cancer that is distinct in primary site or histology from Hepatocellular Carcinoma, except cervical carcinoma in situ, treated basal cell carcinoma, or superficial bladder tumors (Ta, Tis &T1)
  • Presence of hepato pulmonary syndrome
  • Auto immune hemolytic anemia
  • Auto immune disorder, excepted auto immune thyroiditis
  • Uncontrolled hypertension or congestive heart failure
  • Active coronary artery disease (myocardial infarction more than 6 months prior to study entry is permitted)
  • Previous gastrointestinal bleed within the past 2 months
  • Known syndrome AIDS-related illness or serious non controlled acute or chronic illness
  • Active, clinically severe bacterial or fungal infections (> grade 2 CTCAE, version 4.0)
  • Complete initial work up earlier than 4 weeks prior to patient registration
  • Patient whose general health condition does not allow treatment feasibility
  • Patients unable and/or unwilling to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  • Patients participating in another clinical investigation at the time of signature of the informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02721056
Other Study ID Numbers  ICMJE NBTXR3-103
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nanobiotix
Study Sponsor  ICMJE Nanobiotix
Collaborators  ICMJE Quintiles, Inc.
Investigators  ICMJE
Study Director: Mikaela DIMITRIU, PhD Nanobiotix
PRS Account Nanobiotix
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP