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

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ClinicalTrials.gov Identifier: NCT03525392
Recruitment Status : Terminated (Due to agreement to transfer rights for IPN01087 to an external partner, not due to safety concerns)
First Posted : May 15, 2018
Last Update Posted : June 7, 2021
Sponsor:
Information provided by (Responsible Party):
Ipsen

Tracking Information
First Submitted Date  ICMJE May 3, 2018
First Posted Date  ICMJE May 15, 2018
Last Update Posted Date June 7, 2021
Actual Study Start Date  ICMJE May 3, 2018
Actual Primary Completion Date April 3, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
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 ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2021)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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) ]
    Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product
  • 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 60 months (whole study period) ]
    Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product
  • Progression-free survival (PFS) - phase I [ Time Frame: From Day 1 up to the end of the long-term follow up period of 60 months (whole study period) ]
    Determined from start of study treatment until occurrence of event and/or end of observation period
  • Overall survival (OS) - phase I [ Time Frame: From Day 1 up to the end of the long-term follow up period of 60 months (whole study period) ]
    Determined from start of study treatment until occurrence of event and/or end of observation period
  • 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) ]
    In centers where PET scans are part of clinical practice
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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) ]
    Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product
  • 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) ]
    Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product
  • 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) ]
    Determined from start of study treatment until occurrence of event and/or end of observation period
  • 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) ]
    Determined from start of study treatment until occurrence of event and/or end of observation period
  • 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) ]
    In centers where PET scans are part of clinical practice
  • 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) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief Summary

This study was being conducted to advance new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1). This study was a 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, 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 was evaluated. 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 consisted of a phase I dose escalation part. The study originally planned to include a phase II study however due to early termination (not due to safety concerns) the study did not progress to phase II and was stopped during phase I. For the phase I dose escalation part, it was anticipated that approximately 30 subjects will be included, in up to six escalation steps. No expansion cohorts were implemented.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Ductal Adenocarcinoma
  • Colorectal Cancer
  • Gastric Cancer
  • Squamous Cell Carcinoma of the Head and Neck
  • Bone Cancer
  • Advanced Cancer
  • Recurrent Disease
  • Metastatic Tumours
Intervention  ICMJE Drug: 177Lu-3BP-227 (also called 177Lu-IPN01087)
The cumulative activity of the treatment investigational medicinal product (IMP) formulation will be administered in two intravenous (i.v.) infusions separated by at least 4 weeks (28 days). Up to 6 administrations can be given (2 cycles plus 4 optional additional)
Other Name: 177Lu-IPN01087
Study Arms  ICMJE Experimental: 177Lu-3BP-227

Screening: 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).

Intervention: Drug: 177Lu-3BP-227 (also called 177Lu-IPN01087)
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 Terminated
Actual Enrollment  ICMJE
 (submitted: June 2, 2021)
14
Original Estimated Enrollment  ICMJE
 (submitted: May 3, 2018)
300
Actual Study Completion Date  ICMJE April 28, 2021
Actual Primary Completion Date April 3, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria :

  • Signed informed consent form prior to all study procedures
  • Aged 18 years or older.
  • Histologically or cytologically confirmed unresectable locally advanced or metastatic disease and has received prior lines of standard-of-care chemotherapy/treatment and has no further suitable treatment options 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 showing: (a) by uptake of 177Lu-3BP-227 (screening formulation) in known primary or metastatic sites as judged by the investigator to be greater than background; or (b) uptake of 111In 3BP 227 in known primary or metastatic sites (for subjects who participated in Study D FR 01087 002) as judged by the investigator to be greater than background.
  • 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
  • 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 antitumor treatment since last documented 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-characterized.
  • 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 antitumor 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.
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 Belgium,   France,   Netherlands,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03525392
Other Study ID Numbers  ICMJE D-FR-01087-001
2017-001263-20 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ipsen
Study Sponsor  ICMJE Ipsen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ipsen Medical Director Ipsen
PRS Account Ipsen
Verification Date June 2021

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