AzTrials
AzTrials

Liver CancerPhase 1/2NCT02721056

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

A Phase 1/2 study testing NBTXR3, IL or IA injection + SBRT in people with Liver Cancer, run by Nanobiotix at 7 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Cancer
What is being tested?
NBTXR3, IL or IA injection + SBRT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
7 sitesFrance
Study dates
28 Jan 2016to 6 May 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • 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
Show all 59Show fewer
  • 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
  • 700 cc of liver volume without tumor involvement and a radiation therapy dose < 15 Gy
  • 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 rate (PR)> 50%
  • International Normalized Ratio (INR) < 1.5 or correctable with vitamin K. Patients receiving anti-coagulation or anti-aggregation 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 HBV DNA and HCV RNA
  • Serum Creatinine ≤ 1.5 time the upper limit of normal value
  • Glomerular Filtration Rate > 44mL/min/1.73m2
  • All female patients of childbearing potential must have a negative serum/urinary pregnancy test within the 7 days prior to NBTXR3 administration. Otherwise, Patients must be post-menopausal, surgically sterile, or using 'effective contraception'. The definition of 'effective contraception' will be based on the judgment of the investigator.
  • Age ≥ 18
  • Written Informed Consent obtained, signed and dated
  • ECOG performance status 0 or 1
  • Life expectancy > 3 months
  • Histological or cytological diagnosis of Hepatocellular cancer or imaging diagnosis by the American Association for the Study of Liver Disease (AASLD) guidelines or European association for the Study of the Liver (EASL) guidelines.
  • Patients with HCC:
  • Without main branch or intrahepatic trunk portal vein tumor thrombosis (Vp3 or Vp4, respectively), with progression or recurrence of HCC after surgical or loco-regional treatment
  • With main branch (right and/or left) or intrahepatic trunk portal vein tumor thrombosis (Vp3 or Vp4, respectively), AND without right atrial involvement.
  • Recurrent intrahepatic cholangiocarcinoma is eligible only in the phase I part
  • Liver cirrhosis Child Pugh A - B7
  • Previous liver resection or local treatment (radiofrequency ablative therapy, chemoembolization, microwave treatment…) is permitted
  • Patients with previous treatment with sorafenib or other targeted or systemic therapy are eligible if wash out > 4 weeks
  • 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
  • 700 cc of liver volume without tumor involvement and a radiation therapy dose < 15 Gy
  • 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 rate (PR)> 50%
  • International Normalized Ratio (INR) < 1.5 or correctable with vitamin K
  • Patients receiving anti-coagulation or anti-agregant 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 HBV DNA and HCV RNA
  • Serum Creatinine ≤ 1.5 time the upper limit of normal value
  • Glomerular Filtration Rate > 44mL/min/1.73m2
  • All female patients of childbearing potential must have a negative serum/urinary pregnancy test within the 7 days prior to NBTXR3 administration. Otherwise, Patients must be post-menopausal, surgically sterile, or using 'effective contraception'. The definition of 'effective contraception' will be based on the judgment of the investigator.

Who cannot join

  • 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.
Show all 54Show fewer
  • 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
  • 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 NCI-CTCAE, version 5.0)
  • 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.
  • Primary cancer: Hepato Cellular Carcinoma - HCC
  • Patient suitable for a curative treatment by surgery or local treatment (radiofrequency ablation, microwave treatment, etc.)
  • Patients with ongoing chronic active viral B or C hepatitis, those patients 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
  • Extrahepatic Portal Vein Tumor Thrombosis
  • Extra-hepatic metastasis
  • 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
  • Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study. Hormonotherapy is permitted
  • 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
  • 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 NCI-CTCAE, version 5.0)
  • 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. Phase I and II parts target the same liver cancer populations (same inclusion and

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • CHU La Croix Rousse

    Lyon, 69004

  • Institut de Cancérologie de Loraine

    Nancy, 54500

  • CHU de NANCY

    Nancy, 54511

  • Centre René Gauducheau

    Nantes, 44805

  • Hôpital Haut-Lévêque

    Pessac, 33604

  • Centre Eugène Marquis

    Rennes, 35000

  • Institut Gustave Roussy

    Villejuif, 94800

Other trials in France

About this study

Official title: A Phase I-II Study of NBTXR3 Activated by Sterostatic Body Radiation Therapy (SBRT) In the Treatment of Liver Cancers

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.

Read the detailed description

PHASE I PART: Dose escalation and Recommended Dose (Volume) The purpose of the Phase I part of the study is to determine the Recommended Dose (volume), the safety profile and the feasibility of the treatment of NBTXR3 administered either by intrahepatic lesion injection or super selective transcatheter arterial injection and activated by stereotactic body radiation therapy (SBRT), in patients with liver cancers. Primary objective

  • To determine the Recommended Dose(s) (volume(s)) and the early Dose Limiting Toxicity (DLT) of NBTXR3 administered either by intralesional injection or by super selective transcatheter arterial injection and activated by stereotactic body radiation therapy (SBRT) in patients with liver cancers

PHASE II PART: Safety and Efficacy evaluation Primary objectives

The primary objectives of the Phase II part are:

  • To assess and characterize the safety profile, including liver function evaluation using MELD/MELD-Na and Child-Pugh scores, of NBTXR3 activated by SBRT, at the Recommended Dose(s)(Volume(s)) as determined previously in the Phase I part, in patients with liver cancers Clinical Investigation Plan - NBTXR3/103
  • To evaluate the antitumor activity in terms of Complete Response Rate (CRR) of target lesions, as per mRECIST for HCC and RECIST version 1.1 for liver metastases at 12 weeks' post radiotherapy, of NBTXR3 activated by SBRT, at the Recommended Dose(s) (Volume(s)) as determined previously in the Phase I part, in patients with liver cancer.
Conditions
Liver Cancer
Being tested
NBTXR3, IL or IA injection + SBRT
Medical subject headings
Liver Neoplasms

What participants receive

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

  • NBTXR3, IL or IA injection + SBRTRadiation

    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).

Study groups in NCT02721056
Study groupRoleWhat they receive
NBTXR3, IL or IA injection +SBRTExperimental* 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.
Receives: Radiation: NBTXR3, IL or IA injection + SBRT

What is being measured

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

  1. 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)

    Measured: 50 Months

  2. Determination of the early Dose Limiting Toxicities

    To determine the early Dose Limiting Toxicities

    Measured: 50 Months

Secondary outcomes (3)

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

    Measured: 50 Months

  2. Response Rate

    To evaluate the antitumor activity in terms of Response Rate (RR) of target lesions/s, as per mRECIST and RECIST 1.1 criteria

    Measured: 50 Months

  3. Local Progression Free Survival

    To evaluate the local control in terms of local Progression Free Survival

    Measured: 50 Months

Timeline

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

  1. First posted28 Mar 2016 (estimated)
  2. Study start28 Jan 2016
  3. Primary completion6 May 2020
  4. Study completion6 May 2020

Why it stopped: The RP2D for intratumoral injection was determined. With the changing practice of medicine for HCC, it was decided to design an independent Phase II clinical study.

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02721056
Sponsor's protocol ID
NBTXR3-103
Status last verified
Oct 2020
First submitted
24 Dec 2015
Last updated
10 May 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NBTXR3, IL or IA injection + SBRT in people with Liver Cancer, run by Nanobiotix at 7 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 59 inclusion and 54 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The RP2D for intratumoral injection was determined. With the changing practice of medicine for HCC, it was decided to design an independent Phase II clinical study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the Recommended Doses Toxicities (DLT) (time frame: 50 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02721056.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in