A trial to assess efficacy and safety of octreotide subcutaneous depot in patients with GEP-NET

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Camurus AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Sep 2021 → ongoing

Decision date (initial)

2023-12-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-508723-12-00

EudraCT number

2021-000849-40

ClinicalTrials.gov

NCT05050942

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To assess 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)

Secondary objectives 11

1. To assess superiority of treatment with CAM2029 compared to treatment with octreotide LAR or lanreotide ATG with respect to PFS based on local Investigator assessment
2. To compare the 2 treatment groups with respect to overall survival
3. To evaluate the 2 treatment groups with respect to overall response rate (ORR) and disease control rate (DCR)
4. To describe time to tumor response and duration of response in the 2 treatment groups
5. To evaluate the need for rescue medication for symptom control in the 2 treatment groups
6. To assess the pharmacokinetics (PK) of octreotide after CAM2029 administration
7. To assess octreotide exposure–response relationship for CAM2029
8. To assess supervised self- or partner-administration of CAM2029
9. To evaluate patient-reported outcomes (PROs) for health-related quality of life in the 2 treatment groups
10. To evaluate the 2 treatment groups with respect to patient satisfaction with the treatment
11. To confirm the safety and tolerability of CAM2029 in patients with unresectable/metastatic and well-differentiated GEP-NET

Conditions and MedDRA coding

gastroenteropancreatic neuroendocrine tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female patient ≥18 years old
2. Histologically confirmed, advanced (unresectable and/or metastatic), and well-differentiated NET of GEP or presumed GEP origin
3. 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
4. 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
5. ECOG performance status of 0 to 2

Exclusion criteria 13

1. Documented evidence of disease progression while on treatment (including SSAs) for locally advanced unresectable or metastatic disease
2. Known central nervous system metastases
3. Consecutive treatment with long-acting SSAs for more than 6 months before randomization
4. 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
5. 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
6. Treatment of GEP-NET with trans-arterial chemoembolization or trans-arterial embolization within 12 months before screening
7. Previously received radioligand therapy (peptide receptor radionuclide therapy) at any time
8. 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
9. Patients with poorly controlled diabetes, as evidenced by hemoglobin A1c (HbA1c) >8.0%
10. 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
11. 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)
12. 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
13. Any other contraindicated serious medical condition that, in the Investigator's opinion, may prevent the patient from safely participating in the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS, defined as the time from the date of randomization to the date of the first documented disease progression as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first, as assessed by a Blinded Independent Review Committee (BIRC)

Secondary endpoints 14

1. PFS using RECIST 1.1 as assessed by local Investigators
2. Overall survival
3. ORR, defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) as per RECIST 1.1
4. DCR, defined as the proportion of patients with best overall response of CR, PR or stable disease (SD) as per RECIST 1.1
5. Time to response and duration of response as per RECIST 1.1
6. Average number of injections of octreotide rescue medication per month for each patient during the trial
7. Total dosage and dose intensity of rescue medication
8. Octreotide plasma concentrations over time
9. Correlation between octreotide concentration and other endpoints or measures as appropriate
10. Proportion of patients/partners declared competent by trial personnel to administer CAM2029 out of those trying
11. Change from baseline in 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
12. Treatment Satisfaction Questionnaire for Medication (TSQM) scores over time using all 4 domains of TSQM (effectiveness, side effects, convenience, and global satisfaction)
13. Adverse events (AEs) (including local tolerability)
14. Changes in laboratory values, vital signs, electrocardiogram readings

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Camurus AB

Sponsor organisation

Camurus AB

Address

Ideon Science Park

City

Lund

Postcode

223 70

Country

Sweden

Scientific contact point

Organisation

Camurus AB

Contact name

VP Clinical Development.

Public contact point

Organisation

Camurus AB

Contact name

VP Clinical Development.

Third parties 7

Locations

8 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications