Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.
- Conditions
- Recurrent DiseaseBone CancerGastric CancerMetastatic TumoursAdvanced CancerPancreatic Ductal AdenocarcinomaColorectal CancerSquamous Cell Carcinoma of the Head and Neck
- Interventions
- Registration Number
- NCT03525392
- Lead Sponsor
- Ipsen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 14
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 177Lu-3BP-227 177Lu-3BP-227 (also called 177Lu-IPN01087) 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).
- Primary Outcome Measures
Name Time Method Phase 1: Number of Participants With Dose-Limiting Toxicities (DLT) From the start of the first study medication (Cycle 1 Day 1) up to EOCT, maximum of 16 weeks. 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).
- Secondary Outcome Measures
Name Time Method Phase 1: Volume of Distribution of 3BP-227 Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Phase 1: Number of Participants With Objective Response Rate (ORR) From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The ORR was defined as number of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) relative to the total number of evaluable participants.
Phase 1: Metabolic Tumor Response Using Positron Emission Tomography (PET) Response Criteria In Solid Tumors (PERCIST) Version 1.0 or Practical PERCIST From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. Tumor response assessments were planned to perform by the site investigator (local) for the phase 1 and dose escalation part and by independent reader (central) for the phase 2. All fluorine-18 fluorodeoxyglucose-PET images were used for the metabolic tumor response assessments as described in PERCIST version 1.0 by the Investigator and/or independent readers.
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. The pharmacokinetic (PK) sampling was performed from Day 1 to Day 5 post infusion for 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. The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle.
Phase 1: Clearance of 3BP-227 Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Phase 1: Specific Absorbed Dose Per Organ of 177Lu-3BP-227 From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The specific absorbed dose per organ was evaluated by image-based analysis. The specific absorbed dose (Gray/GBq) was calculated as the absorbed dose to an organ (in Gray) divided by the activity of 177Lu-3BP-227 administered (in GBq).
Phase 1: Cumulative Amount of Unchanged 3BP-227 Excreted Into the Urine Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Phase 1: Number of Participants With Disease Control Rate (DCR) From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The DCR was defined as number of participants with a BOR characterized as CR, PR or stable disease according to RECIST 1.1 relative to the total number of evaluable participants.
Phase 1: Renal Clearance of 3BP-227 From Plasma Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
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. The PK sampling was performed from Day 1 to Day 5 post infusion for 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. The PK sampling was performed from Day 1 to Day 5 post infusion for each treatment cycle.
Phase 1: Specific Absorbed Dose to the Target Lesions of 177Lu-3BP-227 From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The specific absorbed dose to the target lesions was evaluated by image-based analysis. Results for all studied diseases (pancreatic ductal adenocarcinoma and colorectal carcinoma) at all anatomical locations (cervical, intrapelvic, liver, lung, lymph node, and pancreas) for all cycles (Cycle 1 and 2) are reported. The specific absorbed dose (Gray/GBq) was calculated as the absorbed dose to the target lesions (in Gray) divided by the activity of 177Lu-3BP-227 administered (in GBq).
Phase 1: Cumulative Absorbed Organ Doses of 177Lu-3BP-227 From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The cumulative absorbed dose to the discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis.
Phase 1: Cmax of 3BP-227 Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Phase 1: AUC of 3BP-227 Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Phase 1: t1/2 of 3BP-227 Pre-infusion and at the end of infusion, and 5 minutes, 30 minutes, 90 minutes, 4 hours, 6 hours, 8 hours, 24 hours and 48 hours post infusion of 177Lu-3BP-227 in Cycle 1. The PK sampling was performed from Day 1 to Day 3 post infusion of 177Lu-3BP-227 in Cycle 1.
Phase 1: Progression-Free Survival (PFS) From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The PFS was defined as the time from date of first study medication administration until progression, according to RECIST 1.1.
Phase 1: Overall Survival (OS) From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The OS was defined from first study medication administration until death, according to RECIST 1.1.
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. 177Lu-3BP-227 uptake in organs and lesions was evaluated centrally, using nuclear medicine images, as part of the dosimetry workflow. Uptake activity for organs of interest (i.e., body, bone marrow, left kidney, right kidney, healthy liver, and spleen) was determined. The uptake activity was expressed relatively to the injected 177Lu-3BP-227 activity calculated as the ratio of the uptake activity divided by the administered activity at the time of injection.
Phase 1: Number of Participants With Highest Absorbed Dose of 177Lu-3BP-227 to Each Discernible Organ From the start of the first study medication (Day 1) up to EOCT, maximum of 16 weeks. The absorbed dose to the target lesions and discernible organs (i.e., organs showing uptake) was evaluated by image-based analysis. The organs considered for 177Lu-3BP-227 image-based dosimetry assessment included: healthy liver, total liver, bone marrow, left kidney, right kidney, intestine (large and small), spleen, pancreas, stomach wall, right ovary, left ovary, uterus, right testis, left testis, thymus, right thyroid gland, left thyroid gland, prostate gland and total body. The organ that had the highest absorbed dose of treatment for each participant in each treatment cycle was determined.
Phase 1: Tumor Marker Levels in Serum - Carcinoembryonic Antigen Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined.
Phase 1: Tumor Marker Levels in Serum - Cancer Antigen 19-9 Cycle 1 Day 1, Cycle 2 Day 1, EOCT (maximum of 16 weeks) and early withdrawal Changes in tumor markers in serum relevant and specific to the underlying tumor disease was determined.
Trial Locations
- Locations (8)
University Medical Center Groningen
🇳🇱Groningen, Netherlands
CHU Vaudois
🇨🇭Lausanne, Switzerland
Universitäts Spital Zürich
🇨🇭Zürich, Switzerland
CHU Timone
🇫🇷Marseille, France
CHU Hôtel Dieu
🇫🇷Nantes, France
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Centre Léon Bérard
🇫🇷Lyon, France
Institut Jules Bordet
🇧🇪Brussels, Belgium