Phase 3 Trial of Octreotide Subcutaneous Depot vs. Octreotide LAR or Lanreotide ATG in Unresectable/Metastatic GEP-NET Patients
- Trial ID
- 2023-508723-12-00
- Protocol
- HS-19-657
- Sponsor
- Camurus AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **superiority** of treatment with CAM2029 compared to treatment with octreotide long-acting release (LAR) or lanreotide autogel (ATG) on progression-free survival (PFS) in patients with unresectable/metastatic and well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). This is clinically relevant as improving PFS can significantly impact the management and prognosis of patients with GEP-NET, offering potential advancements in therapeutic strategies.
Secondary objectives include:
- Assessing the superiority of CAM2029 over octreotide LAR or lanreotide ATG with respect to PFS based on local investigator assessment.
- Comparing the two treatment groups with respect to overall survival.
- Evaluating the two treatment groups concerning overall response rate (ORR) and disease control rate (DCR).
- Describing time to tumor response and duration of response in the two treatment groups.
- Evaluating the need for rescue medication for symptom control in the two treatment groups.
- Assessing the pharmacokinetics (PK) of octreotide after CAM2029 administration.
- Assessing the octreotide exposure–response relationship for CAM2029.
- Assessing supervised self- or partner-administration of CAM2029.
- Evaluating patient-reported outcomes (PROs) for health-related quality of life in the two treatment groups.
- Evaluating the two treatment groups with respect to patient satisfaction with the treatment.
- Confirming the safety and tolerability of CAM2029 in patients with unresectable/metastatic and well-differentiated GEP-NET.
Participants
The clinical trial involves a total of **68 participants** diagnosed with **gastroenteropancreatic neuroendocrine tumors** (GEP-NET). The study population includes both male and female subjects aged 18 years and older, with a focus on individuals with advanced, unresectable, and well-differentiated tumors. Participants were selected based on specific criteria, including having at least one measurable, somatostatin receptor-positive lesion and an ECOG performance status of 0 to 2. The trial does not specify particular lifestyle considerations such as diet or physical activity. The population includes vulnerable groups, ensuring a comprehensive assessment of the treatment's efficacy across diverse demographics.
Plans and Procedures
The clinical trial is a **randomized**, multi-center, open-label, active-controlled Phase 3 study designed to evaluate the efficacy and safety of **octreotide subcutaneous depot** (CAM2029) compared to **octreotide long-acting release** (LAR) or **lanreotide autogel** (ATG) in patients with **gastroenteropancreatic neuroendocrine tumors** (GEP-NET). The primary objective is to assess the superiority of CAM2029 in terms of progression-free survival (PFS) in patients with unresectable or metastatic and well-differentiated GEP-NET. The trial is expected to run from October 2021 to December 2026, with a maximum treatment period of 72 weeks for CAM2029 and 48 weeks for the comparator drugs.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of GEP-NET, and somatostatin receptor-positive lesions. Following randomization, participants will attend regular follow-up visits to monitor treatment efficacy and safety, including assessments of PFS, overall survival, and objective response rate (ORR) as per RECIST 1.1 criteria. The end-of-study visit will conclude the participant's involvement, with evaluations of treatment satisfaction and quality of life.
The expected length of participant involvement is up to 72 weeks, depending on the treatment arm. Conditions that may lead to early termination from the study include disease progression, unacceptable adverse events, or withdrawal of consent. The trial will utilize a Blinded Independent Review Committee (BIRC) to assess primary endpoints, ensuring unbiased evaluation of disease progression or death. Secondary endpoints include overall survival, duration of response, and changes in quality of life, among others. The study will also monitor adverse events and changes in laboratory values, vital signs, and electrocardiogram readings to ensure participant safety throughout the trial.
Treatment
The clinical trial involves the administration of **Somatuline Autogel 120 mg**, a **solution for injection** in a pre-filled syringe, containing the active substance **lanreotide**. This medication is administered via **subcutaneous injection**. The maximum daily dose is 120 mg, with a total maximum dose of 6240 mg over a treatment period of 48 weeks. The product is manufactured by IPSEN PHARMACEUTICALS LTD. and is not a pediatric formulation. The pharmaceutical form is a solution for injection, and the product is classified under the ATC code H01CB03.
Another treatment in the trial is **CAM2029 (octreotide subcutaneous depot)**, which is also a **solution for injection**. The active substance is **octreotide hydrochloride**, and it is administered via **subcutaneous injection**. The maximum daily dose is 20 mg, with a total maximum dose of 6000 mg over a treatment period of 72 weeks. This product is developed by CAMURUS AB and is not a pediatric formulation. The device used for administration includes pre-sterilized ready-to-fill syringes with a safety device for post-injection needle stick prevention.
The trial also includes **SANDOSTATIN LAR 30 mg**, a **powder and solvent for suspension for injection**, containing the active substance **octreotide**. This medication is administered via **intramuscular injection**. The maximum daily dose is 30 mg, with a total maximum dose of 1560 mg over a treatment period of 48 weeks. The product is manufactured by NOVARTIS IRELAND LIMITED and is not a pediatric formulation. The device used for administration includes a pre-filled syringe with an automatic safety system to prevent needle stick injuries post-injection.
Efficacy
The efficacy of the treatment in this clinical trial will be assessed primarily through **Progression-Free Survival (PFS)**. PFS is defined as the time from the date of randomization to the date of the first documented disease progression, as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), or death due to any cause, whichever occurs first. This primary endpoint will be evaluated by a Blinded Independent Review Committee (BIRC).
Secondary efficacy endpoints include PFS as assessed by local investigators, overall survival, and objective response rate (ORR), which is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. Additionally, the disease control rate (DCR), time to response, and duration of response will be measured. The trial will also assess the average number of injections of octreotide rescue medication per month, total dosage and dose intensity of rescue medication, and octreotide plasma concentrations over time. The correlation between octreotide concentration and other endpoints or measures will be evaluated as appropriate.
Patient-reported outcomes will be collected using the Quality of Life Questionnaire – Neuroendocrine Carcinoid Module (QLQ-GINET21), Short Form-36 (SF-36), and the global health status/quality of life scale score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30). Treatment satisfaction will be measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) scores over time, covering all four domains: effectiveness, side effects, convenience, and global satisfaction. Adverse events, including local tolerability, changes in laboratory values, vital signs, and electrocardiogram readings, will also be monitored throughout the trial.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female patient ≥18 years old
- Histologically confirmed, advanced (unresectable and/or metastatic), and well-differentiated NET of GEP or presumed GEP origin
- At least 1 measurable, somatostatin receptor-positive*, lesion according to RECIST 1.1 determined by multiphasic CT or MRI (performed within 28 days before randomization) *Somatostatin-receptor imaging must be performed within 12 months before randomization. Somatostatin receptor-positive lesions are defined as lesions with a visual assessment of uptake greater than the liver
- Results from FDG-PET CT for patients with well-differentiated Grade 3 NET (if performed) must show that FDG avid areas of disease also are avid on somatostatin-receptor imaging
- ECOG performance status of 0 to 2
Exclusion Criteria
- Documented evidence of disease progression while on treatment (including SSAs) for locally advanced unresectable or metastatic disease
- Known central nervous system metastases
- Consecutive treatment with long-acting SSAs for more than 6 months before randomization
- Carcinoid symptoms that are refractory to treatment (according to the Investigator's judgement) with conventional doses of octreotide LAR or lanreotide ATG and/or to treatment with daily doses of ≤600 μg of octreotide IR
- Previous treatment with more than 1 cycle (where 1 cycle means ≤28 days on treatment) of targeted therapies such as mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus, temsirolimus, or everolimus) or vascular endothelial growth factor inhibitors (e.g. sunitinib, lenvatinib, or cabozantinib), or more than 1 cycle of chemotherapy or interferon for GEP-NET
- Treatment of GEP-NET with trans-arterial chemoembolization or trans-arterial embolization within 12 months before screening
- Previously received radioligand therapy (peptide receptor radionuclide therapy) at any time
- Hepatic/pancreatic-related exclusion criteria: ○ Active hepatitis. Patients with no significant viral load, no acute signs of inflammation, and no clinical necessity for therapy are allowed, at the Investigator’s discretion ○ Symptomatic cholelithiasis ○ Clinically active or chronic liver disease, including liver cirrhosis of Child-Pugh class B or C
- Patients with poorly controlled diabetes, as evidenced by hemoglobin A1c (HbA1c) >8.0%
- Cardiac history or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the trial, such as uncontrolled or significant cardiac disease, including any of the following: ○ History of myocardial infarction, unstable angina pectoris, or coronary artery bypass graft within 6 months before screening ○ Uncontrolled congestive heart failure
- Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, or high-grade atrioventricular block (e.g. bifascicular block, Mobitz type II, and third-degree atrioventricular block)
- Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: ○ Risk factors for Torsades de Pointes, including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ○ Treatment with concomitant medication(s) with a "known risk of Torsades de Pointes" per www.crediblemeds.org that cannot be discontinued or replaced with safe alternative medication at least 7 days or 5 half-lives (whichever is longer) before start of IMP treatment ○ Patients with a QTc interval corrected by Fridericia's formula >450 msec for males and >470 msec for females at screening
- Any other contraindicated serious medical condition that, in the Investigator's opinion, may prevent the patient from safely participating in the trial
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 22 Oct 2021 | 30 |
 France | Not Recruiting | 22 Oct 2021 | 35 |
 Germany | Not Recruiting | 22 Oct 2021 | 22 |
 Hungary | Not Recruiting | 22 Oct 2021 | 20 |
 Italy | Not Recruiting | 22 Oct 2021 | 49 |
 The Netherlands | Not Recruiting | 22 Oct 2021 | — |
 Romania | Not Recruiting | 22 Oct 2021 | 5 |
 Spain | Not Recruiting | 22 Oct 2021 | 52 |
| Netherlands | — | — | 21 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Oczyesa 20 mg prolonged-release solution for injection in pre-filled pen | Test | PROLONGED-RELEASE SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | 20 | 72 | PRD12641913 |
SANDOSTATIN LAR 30 mg powder and solvent for suspension for injection | Comparator | POWDER AND SOLVENT FOR SUSPENSION FOR INJECTION | SUBCUTANEOUS INJECTION | 20 | 72 | PRD6476474 |
Somatuline Autogel 120 mg, solution for injection in a pre-filled syringe | Comparator | SOLUTION FOR INJECTION IN A PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 120 | 48 | PRD391357 |