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

NCT03525392 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: D-FR-01087-0012017-001263-20
• Study Type: interventional
• Target: 14
• Locations: 5 countries
• Sites: 8

Brief Summary

This study was conducted to advance new treatment for patients with metastatic or locally advanced cancers expressing Neurotensin receptor 1 (NTSR1). This study was the first time the investigational drug called 177Lu-3BP-227 was administered to patients under controlled conditions of a clinical study. The purpose of this study was to evaluate how safe the 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 also 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT)

  DLTs were defined for a list of predefined study medication-related adverse events (AEs) as specified in the protocol, according to the National Cancer Institute - Common Terminology Criteria for Adverse Events scale version 5.0 that occurred during the defined DLT assessment period (during Cycle 1 or 2).

  From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks.

Secondary Outcomes (23)

• Phase 1: Maximum Uptake (%) of 177Lu-3BP-227 at Target Lesions and Discernible Organs

  Measurements were performed at 0 to 1 hours, 2 to 4 hours, 16 to 24 hours, 40 to 48 hours, 72 to 96 hours post infusion in each treatment cycle.

• Phase 1: Maximal Concentration (Cmax) of 177Lu-3BP-227

  Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.

• Phase 1: Time Post Injection to Achieve Cmax of 177Lu-3BP-227

  Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.

• Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of 177Lu-3BP-227

  Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.

• Phase 1: Half-life (t1/2) of 177Lu-3BP-227

  Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 24 hours, 48 hours and 72 to 96 hours post infusion in each treatment cycle.

Study Arms (1)

177Lu-3BP-227

EXPERIMENTAL

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)

Interventions

177Lu-3BP-227 (also called 177Lu-IPN01087) DRUG

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)

Also known as: 177Lu-IPN01087

177Lu-3BP-227

Eligibility Criteria

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

You may qualify if:

• 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 adenocarcinoma (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.

You may not qualify if:

• 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 kidneys.
• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (8)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Centre Léon Bérard

Lyon, France

Location

CHU Timone

Marseille, 13385, France

Location

CHU Hôtel Dieu

Nantes, France

Location

University Medical Center Groningen

Groningen, 9713, Netherlands

Location

CHU Vaudois

Lausanne, Switzerland

Location

Universitäts Spital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms; Squamous Cell Carcinoma of Head and Neck; Bone Neoplasms; Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Bone Diseases; Musculoskeletal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Limitations and Caveats

The sponsor terminated the study early and phase 1 dose expansion and phase 2 were not started. The decision to terminate the study was not due to any safety or tolerability concern, or any event associated with the use of 177Lu-3BP-227.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen Pharma SAS

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: May 15, 2018
• Study Start: May 3, 2018
• Primary Completion: April 3, 2020
• Study Completion: April 28, 2021
• Last Updated: December 12, 2023
• Results First Posted: December 12, 2023

Record last verified: 2023-02

Locations

BE (1); CH (2); US (1); NL (1); FR (3)