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

NCT02721056 | Terminated Phase 1 DMC

• 1 other identifier: NBTXR3-103
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 7

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.

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (2)

• Determination of the Recommended Doses Toxicities (DLT)

  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)

  50 Months

• Determination of the early Dose Limiting Toxicities

  To determine the early Dose Limiting Toxicities

  50 Months

Secondary Outcomes (3)

• Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

  50 Months

• Response Rate

  50 Months

• Local Progression Free Survival

  50 Months

Study Arms (1)

NBTXR3, IL or IA injection +SBRT

EXPERIMENTAL

* Patients will receive a single intralesional (IL) injection of NBTXR3 at four increasing dose levels (Volume levels) equivalent to: 10%, 15%, 22%, 33% and 42% 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.

Radiation: NBTXR3, IL or IA injection + SBRT

Interventions

NBTXR3, IL or IA injection + SBRT RADIATION

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 45 or 50 Gy, delivered as three fractions of 15 Gy or 5 fractions of 10 Gy each, over 5 to 15 days (45 or 50Gy, 15GyX3 or 10GyX5).

NBTXR3, IL or IA injection +SBRT

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18
• Written Informed Consent obtained, signed and dated
• ECOG performance status 0 or 1
• Life expectancy \> 6 months
• Liver metastases from other primary cancers 1) with histologic confirmation of metastases, or 2) History of primary cancer with histology available and 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)
• Radiological disease progression according to the investigator evaluation or according to RECIST 1.1
• 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)
• Total target volume of lesions \< 500cc and \< 50% of the total liver volume
• cc of liver volume without tumor involvement and a radiation therapy dose \< 15 Gy
• The following laboratory parameters:

You may not qualify if:

• Patients with ongoing chronic active viral B or C hepatitis must have received an antiviral treatment with negative 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 in the same hepatic lobe than the current tumor.
• Previous intra-arterial chemotherapy
• Prior radiation therapy to the right upper abdomen, precluding re-irradiation 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-venous intra tumoral shunting
• Encephalopathy related to liver failure
• Clinical ascitis
• Presence of another scalable tumor disease 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

Sponsors & Collaborators

• Nanobiotix: lead

Study Sites (7)

CHU La Croix Rousse

Lyon, 69004, France

Location

Institut de Cancérologie de Loraine

Nancy, 54500, France

Location

CHU de NANCY

Nancy, 54511, France

Location

Centre René Gauducheau

Nantes, 44805, France

Location

Hôpital Haut-Lévêque

Pessac, 33604, France

Location

Centre Eugène Marquis

Rennes, 35000, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Design

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

Model Details: Dose escalation (volume) of NBTXR3 (SBRT 45 Gy \[15 Gy x 3 fractions over 5 - 7 days\] or 50 Gy \[10 Gy x 5 fractions over 5 - 15 days\]), to define the early dose limiting toxicities (DLTs) and the recommended dose (volume) for further development.

Study Record Dates

• First Submitted: December 24, 2015
• First Posted: March 28, 2016
• Study Start: January 28, 2016
• Primary Completion: May 6, 2020
• Study Completion: May 6, 2020
• Last Updated: May 10, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)