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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 : Recruiting
First Posted : May 15, 2018
Last Update Posted : June 11, 2018
Sponsor:
Information provided by (Responsible Party):
Ipsen

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma Colorectal Cancer Gastric Cancer Squamous Cell Carcinoma of the Head and Neck Bone Cancer Advanced Cancer Recurrent Disease Metastatic Tumours Drug: 177Lu-3BP-227 (also called 177Lu-IPN01087) Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 3, 2018
Estimated Primary Completion Date : September 27, 2021
Estimated Study Completion Date : November 22, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 available 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) GC, or (d) SCCHN
  • Tumour tissue expressing NTSR1 as determined by uptake of 177Lu-3BP-227 (screening formulation) in tumour lesions being higher than in non-tumoral liver tissue based on SPECT/CT as per investigator's judgement.
  • Measurable disease (based on RECIST version1.1).
  • Tumour biopsy obtained during screening period or in the 21 days prior to Informed consent signature and after the end of previous treatment.
  • Documentation of progressive disease in the 6 months prior to study start (treatment).
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Adequate organ function as evidenced by: (a) Leukocytes ≥4000/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) epidermal growth factor receptor (eGFR) ≥55 mL/min.
  • Estimated life expectancy >3 months.
  • Female subjects of childbearing potential must agree to use an adequate double-barrier method of contraception during the study and for 30 days after discharge. Adequate methods of contraception for subjects or their partners include vasectomised partner (at least 6 months prior to dosing); intrauterine device; condom with spermicidal gel, foam, cream, film, or suppository; diaphragm with spermicidal gel, foam, cream, film, or suppository; or cervical cap with spermicidal gel, foam, cream, film, or suppository Female subjects of childbearing potential are defined as those who have not undergone surgical sterilisation, or those who are not considered postmenopausal. Postmenopause is defined as absence of menstruation for at least 2 years. If necessary, follicle stimulating hormone results >50 IU/L at screening are confirmatory in the absence of a clear postmenopausal history.
  • For male subjects, agreement that, if a partner is of childbearing potential, a medically accepted and effective method of contraception (i.e. condom) will be used for the duration of the study.
  • 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 a cycle interval prior to first treatment IMP administration (c) Any curative radiotherapy within 4 weeks, or palliative radiotherapy within 7 days prior to first treatment IMP administration (d) Any other IMP within five half-lives of the previous IMP or within 2 weeks prior to first treatment IMP administration, if the previous compound is a mechanism based molecularly targeted agent whose half-life is not well characterised.
  • Brain metastases.
  • 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.
  • Body weight <50 kg.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03525392


Contacts
Contact: Ipsen Recruitment Enquiries clinical.trials@ipsen.com

Locations
France
CHU Hôtel Dieu Recruiting
Nantes, France
Sponsors and Collaborators
Ipsen
Investigators
Study Director: Mona Wahba Ipsen

Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT03525392     History of Changes
Other Study ID Numbers: D-FR-01087-001
2017-001263-20 ( EudraCT Number )
First Posted: May 15, 2018    Key Record Dates
Last Update Posted: June 11, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Bone Neoplasms
Colorectal Neoplasms
Carcinoma, Squamous Cell
Adenocarcinoma
Stomach Neoplasms
Head and Neck Neoplasms
Neoplasm Metastasis
Osteosarcoma
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Stomach Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue