Clinical Trials /

Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.

NCT03525392

Description:

This study is being done because new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1) is being studied. This study will be the first administration of a radioactive drug called 177Lu-3BP-227 to patients under controlled conditions of a clinical study. The purpose of this study is to evaluate how safe this investigational drug is as well to verify how well it is tolerated by patients after several intravenous administrations. In addition, we will evaluate the effect of the study drug on tumoral lesions and how it distributes throughout the body and at which rate it is removed from the body. Since 177Lu-3BP-227 is a radio-labelled drug, it will also be measured how the emitted radiation is distributed throughout the body (dosimetry). The study consists of a phase I with a dose escalation part (and potential expansion cohorts) and a phase II either in selected or over multiple indications in a basket approach. For the dose escalation part, it is anticipated that approximately 30 subjects will be included, in up to six escalation steps. In case of the implementation of phase I expansion cohorts, up to 45 additional subjects will be enrolled. For the phase II, approximately 125 subjects (55 Pancreatic ductal adenocarcinoma and 70 Colorectal cancer subjects) are planned to be enrolled for Basket trial or Optimal Simon's Two Stage design. If additional cohorts of subjects with Gastric cancer (GC) or Squamous-cell carcinoma of head and neck (SCCHN) in the phase II are to be studied, approximately 100 additional subjects will be enrolled.

Related Conditions:
  • Colorectal Carcinoma
  • Ewing Sarcoma
  • Gastric Adenocarcinoma
  • Gastrointestinal Stromal Tumor
  • Head and Neck Squamous Cell Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.
  • Official Title: An International Multicentre, Open-Label First in Human Phase I/II Study to Evaluate the Safety, Tolerability, Biodistribution and Antitumour Activity of 177Lu-3BP-227 for the Treatment of Subjects With Solid Tumours Expressing Neurotensin Receptor 1

Clinical Trial IDs

  • ORG STUDY ID: D-FR-01087-001
  • SECONDARY ID: 2017-001263-20
  • NCT ID: NCT03525392

Conditions

  • Pancreatic Ductal Adenocarcinoma
  • Colorectal Cancer
  • Gastric Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Bone Cancer
  • Advanced Cancer
  • Recurrent Disease
  • Metastatic Tumours

Interventions

DrugSynonymsArms
177Lu-3BP-227 (also called 177Lu-IPN01087)177Lu-IPN01087177Lu-3BP-227

Purpose

This study is being done because new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1) is being studied. This study will be the first administration of a radioactive drug called 177Lu-3BP-227 to patients under controlled conditions of a clinical study. The purpose of this study is to evaluate how safe this investigational drug is as well to verify how well it is tolerated by patients after several intravenous administrations. In addition, we will evaluate the effect of the study drug on tumoral lesions and how it distributes throughout the body and at which rate it is removed from the body. Since 177Lu-3BP-227 is a radio-labelled drug, it will also be measured how the emitted radiation is distributed throughout the body (dosimetry). The study consists of a phase I with a dose escalation part (and potential expansion cohorts) and a phase II either in selected or over multiple indications in a basket approach. For the dose escalation part, it is anticipated that approximately 30 subjects will be included, in up to six escalation steps. In case of the implementation of phase I expansion cohorts, up to 45 additional subjects will be enrolled. For the phase II, approximately 125 subjects (55 Pancreatic ductal adenocarcinoma and 70 Colorectal cancer subjects) are planned to be enrolled for Basket trial or Optimal Simon's Two Stage design. If additional cohorts of subjects with Gastric cancer (GC) or Squamous-cell carcinoma of head and neck (SCCHN) in the phase II are to be studied, approximately 100 additional subjects will be enrolled.

Trial Arms

NameTypeDescriptionInterventions
177Lu-3BP-227ExperimentalScreening: 177Lu-IPN01087 - 25 µg 3BP-227 (IPN01087) per 1 GBq of 177Lu. 1 GBq in a total volume of 10 mL. Treatment phase: 177Lu-IPN01087 - 2.5 to 7.5 GBq escalation dose of 177Lu-3BP-227 (IPN01087) in a total volume of 20 mL for each cycle of administration (2 cycles plus 4 optional additional).
  • 177Lu-3BP-227 (also called 177Lu-IPN01087)

Eligibility Criteria

        Inclusion Criteria :

          -  Signed informed consent form prior to all study procedures

          -  Aged 18 years or older.

          -  Histologically or cytologically confirmed metastatic or locally advanced disease and
             no compelling treatment option as per standard-of-care and documented decision by a
             multidisciplinary oncology board including a specialist of the concerned pathology.

          -  Subjects have: (a) pancreatic ductal adenocarcinoma (PDAC), or (b) colorectal cancer
             (CRC), or (c) gastric adenocarcinoma (GC), or (d) gastrointestinal stromal tumours
             (GIST), or (e) squamous-cell carcinoma of head and neck (SCCHN), or (f) Ewing Sarcoma
             (ES)

          -  Tumour tissue expressing NTSR1 as determined by uptake of 177Lu-3BP-227 (screening
             formulation) in tumour lesions judged by the investigator to more avid than in the
             non-tumoral surrounding tissue based on whole body scan (planar scintigraphy); single
             photon emission computed tomography (SPECT)/ computed tomography (CT) can be performed
             as per investigator's judgement.

          -  Measurable disease (based on RECIST version1.1).

          -  Documentation of progressive disease in the 6 months prior to study start (treatment).

          -  Eastern Cooperative Oncology Group performance status of 0 or 1 (unless if disability
             is related to surgery in ES and Agreed with the Sponsor).

          -  Adequate organ function as evidenced by: (a) Leukocytes ≥3000/μL (b) Absolute
             neutrophil count ≥1500/µL (c) Platelets ≥75,000/µL (d) Hb >9 g/dL or >10 g/dL (if
             history of cardiac disease) (e) Total serum bilirubin ≤2 times upper normal
             institutional limits (ULN) (f) Aspartate aminotransferase/alanine aminotransferase
             (ALT) ≤2.5×ULN (or ≤5×ULN, if subject has liver metastases) (g) Estimated glomerular
             filtration rate (eGFR) ≥55 mL/min.

          -  Estimated life expectancy >3 months.

          -  Female subjects must not be pregnant or lactating at study entry and during the course
             of the study and must not become pregnant for at least 6 months following the last
             study treatment. Women of childbearing potential must agree to use a highly effective
             method of contraception. Because CT scanning is part of the long-term follow-up (every
             12 ±2 weeks), female subjects should not become pregnant until the end of study
             assessments.

          -  For male subjects, must not father children during the study and for at least 6 months
             after the last study treatment and in addition must agree to use a condom for this
             period to protect his partner from contamination with the IMP. For males with partners
             who are of child bearing potential, effective contraception is a combination of male
             condom with either cap, diaphragm or sponge with spermicide (double barrier methods),
             but these are not considered to be highly effective. A man is considered to be
             infertile if he has had bilateral orchidectomy or successful vasectomy. Effective
             contraception includes a female partner of childbearing potential if she is using
             highly efficacious contraception, but the male subject must agree to use a condom to
             protect his partner as described above.

          -  Must be willing and able to comply with study restrictions and to remain at the clinic
             for the required time during the study period and willing to return to the clinic for
             the follow-up evaluation, as specified in the protocol.

        Exclusion Criteria :

          -  Prior treatment received (a) Any antitumour treatment since last documentation of
             disease progression (b) Any chemotherapy within 3 weeks or nitrosourea within 6 weeks
             prior to first treatment investigational medicinal product (IMP) administration (c)
             Any curative radiotherapy within 4 weeks, or palliative radiotherapy within 7 days
             prior to first treatment IMP administration (d) Any monoclonal antibodies within 4
             weeks or tyrosine kinases inhibitors within 2 weeks prior to the first treatment IMP
             administration, (e) Any other IMP within 2 weeks prior to first treatment IMP
             administration, if the previous compound is a mechanism-based molecularly targeted
             agent whose half-life (t1/2) is not well-characterised.

          -  Brain metastases.

          -  Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject
             at high risk of renal toxicity during the study.

          -  Only non measurable metastatic bone lesions

          -  Existing or planned colostomy during study participation.

          -  Any history of inflammatory bowel disease.

          -  Any uncontrolled significant medical, psychiatric or surgical condition or laboratory
             finding, that would pose a risk to subject safety or interfere with study
             participation or interpretation of individual subject results.

          -  Clinically significant abnormalities on electrocardiogram (ECG) at screening including
             corrected QT interval (Fridericia's formula) >450 msec for males or 470 msec for
             females at screening.

          -  Previously received external beam irradiation to a field that includes more than 30%
             of the bone marrow or kidney.

          -  Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia) from previous
             antitumour treatment and/or medical/surgical procedures/interventions.

          -  Known allergy to IMP or its excipients administered in this study, including imaging
             contrast media.

          -  Positive pregnancy test (female subjects).

          -  Likely to be uncompliant or uncooperative during the study, in the judgment of the
             investigator.

          -  Unable to understand the nature, scope and possible consequences of the study, in the
             judgment of the investigator.

          -  Sponsor employees or investigator site personnel directly affiliated with this study,
             and their immediate families. Immediate family is defined as a spouse, parent, child
             or sibling, whether biological or legally adopted.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs) and organ exposure to radiation - phase I
Time Frame:From Day 1 (first administration) up to 6 weeks after the second administration
Safety Issue:
Description:DLTs are defined for Investigational Medicinal Product (IMP) related AEs according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale version 4.03. Criteria for Adverse Events (NCI-CTCAE) scale version 4.03

Secondary Outcome Measures

Measure:Maximal uptake (%) of 177Lu-3BP-227 at target lesions and discernible organs - phase I
Time Frame:During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment)
Safety Issue:
Description:
Measure:Highest absorbed dose to the target lesions (Gy/GBq) of 177Lu-3BP-227 - phase I
Time Frame:During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment)
Safety Issue:
Description:
Measure:Specific absorbed per organ (Gy/GBq) of 177Lu-3BP-227 - phase I
Time Frame:During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment)
Safety Issue:
Description:
Measure:Cumulative absorbed organ doses (Gy) of 177Lu-3BP-227 - phase I
Time Frame:During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment)
Safety Issue:
Description:
Measure:Observed maximal (peak) concentration (Cmax) of 3BP-227 - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Area under the (plasma concentration versus time) curve (AUC) of 3BP-227 - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Half-life (t1/2) of 3BP-227 - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Clearance (CL) of 3BP-227 - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Volume of distribution (Vd) of 3BP-227 - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Cumulative amount of unchanged drug excreted into the urine (Ae) - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Renal clearance of 177Lu-3BP-227 from plasma (CLR), as measured in plasma and urine - phase I
Time Frame:Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion
Safety Issue:
Description:
Measure:Objective response rate of 177Lu-3BP-227 - phase I
Time Frame:From Day 1 up to 16 weeks (starts at the first administration and ends 6 weeks after the second administration)
Safety Issue:
Description:Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product
Measure:Disease control rate of 177Lu-3BP-227 - phase I
Time Frame:From Day 1 up to the end of the long-term follow up period of 24 months (whole study period)
Safety Issue:
Description:Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product
Measure:Progression-free survival (PFS) - phase I
Time Frame:From Day 1 up to the end of the long-term follow up period of 24 months (whole study period)
Safety Issue:
Description:Determined from start of study treatment until occurrence of event and/or end of observation period
Measure:Overall survival (OS) - phase I
Time Frame:From Day 1 up to the end of the long-term follow up period of 24 months (whole study period)
Safety Issue:
Description:Determined from start of study treatment until occurrence of event and/or end of observation period
Measure:Evaluation of metabolic tumour response using Positron emission tomography (PET) Response Criteria In Solid Tumours (version 1.0) or practical PERCIST - phase I
Time Frame:From Day 1 up to 16 weeks (starts at the first administration and ends 6 weeks after the second administration)
Safety Issue:
Description:In centers where PET scans are part of clinical practice
Measure:Changes in serum tumour markers relevant and specific to the underlying tumour disease - phase I
Time Frame:From Day 1 up to 16 weeks (starts at the first administration and ends 6 weeks after the second administration)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ipsen

Last Updated

August 27, 2020