This study has been transitioned to CTIS with ID 2023-508723-12-00 check the CTIS register for the current data. Primary Objective• To assess superiority of treatment with CAM2029 compared to treatment with octreotide long-acting release (LAR) or…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint
• 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 outcome
Secondary Endpoints
• PFS using RECIST 1.1 as assessed by local Investigators
• Overall survival
• ORR, defined as the proportion of patients with best overall response of
complete response (CR) or partial response (PR) as per RECIST 1.1
• DCR, defined as the proportion of patients with best overall response of CR,
PR or stable disease (SD) as per RECIST 1.1
• Time to response and duration of response as per RECIST 1.1
• Average number of injections of octreotide rescue medication per month for
each patient during the trial
• Total dosage and dose intensity of rescue medication
• Octreotide plasma concentrations over time
• Correlation between octreotide concentration and other endpoints or measures
as appropriate
• Proportion of patients/partners declared competent by trial personnel to
administer CAM2029 out of those trying
• 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)
• Treatment Satisfaction Questionnaire for Medication (TSQM) scores over time
using all 4 domains of TSQM (effectiveness, side effects, convenience, and
global satisfaction)
• Adverse events (AEs) (including local tolerability)
• Changes in laboratory values, vital signs, electrocardiogram readings and
gallbladder imaging
Exploratory Endpoints
• Progression-free survival in the Extension Treatment Period (PFS-ext),
defined as time from date of randomization to the date of documented disease
progression as per RECIST 1.1 or death from any cause, whichever occurs first,
in the Open-label Extension Treatment Period, as assessed by a BIRC
• PFS2, defined as time from date of randomization to the date of documented
progression as per RECIST 1.1 on next-line therapy or death from any cause,
whichever occurs first
• Number of patients hospitalized
• Total number and length of hospitalizations
• Describe patients* experiences with the trial regimen and trial activities
using data from patient exit interviews
• Explore the minimal important difference for EORTC QLQ-C30 using patient exit
interviews
• To explore the minimal important difference for EORTC QLQ-C30 using the
Patient Global Impression of Severity (PGI-S) and patient exit interviews
• Time to deterioration of ECOG performance status
• Qualification and quantification of anti-octreotide antibodies
Background summary
CAM2029 is an experimental drug, which means it is not approved by Health
Authorities (such as Ministerie van volksgezondheid, welzijn en sport) for the
treatment of GEP-NET. However, other drugs that contain the active substance
(octreotide) that is used in CAM2029 are currently approved by health
authorities for the treatment of GEP-NET and other diseases and conditions.
CAM2029 is a long-acting product with octreotide (a hormone drug that is used
to treat some tumors) which is administered under the skin (subcutaneously) to
create a depot. The octreotide is slowly released from this depot, which may
lead to stable therapeutic levels in the blood; stable level may be achieved
after 2nd injection. CAM2029 is provided in a ready-to-use syringe or pen at
the dose of 20 mg. Both the syringe and pen have a thin needle and the volume
of the dose is small. It also offers an option for a potentially easier and
convenient way of administration as the drug can be given by you or your
partner/caregiver.
Octreotide LAR and lanreotide ATG are both approved by Health Authorities in
The Netherlands for the treatment of GEP-NET. The products containing these two
formulations may be sold under many different brand names in your country (such
as Sandostatin LAR, Somatuline, etc.).
Neuroendocrine tumors (NET) are rare tumors that develop in cells of the
neuroendocrine system. There is a number of different types of NET. The type of
NET depends on the particular cells where the tumor starts. You have been
diagnosed with NET that is believed to have started in the pancreas or other
parts of the gastrointestinal tract. The current standard of care treatment for
GEP-NET is a medicine called somatostatin analogues (SSAs). SSAs are drugs that
stop the body from making too much hormone. The SSAs stop or reduce the
increase of NET cells that may produce such hormones. Some NET make large
amounts of hormone. Octreotide LAR and lanreotide ATG are classified as SSAs
and work similarly to natural somatostatin.
Study objective
This study has been transitioned to CTIS with ID 2023-508723-12-00 check the CTIS register for the current data.
Primary Objective
• 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
• 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
• To compare the 2 treatment groups with respect to overall survival
• To evaluate the 2 treatment groups with respect to overall response rate
(ORR) and disease control rate (DCR)
• To describe time to tumor response and duration of response in the 2
treatment groups
• To evaluate the need for rescue medication for symptom control in the 2
treatment groups
• To assess the pharmacokinetics (PK) of octreotide after CAM2029 administration
• To assess octreotide exposure-response relationship for CAM2029
• To assess supervised self- or partner-administration of CAM2029
• To evaluate patient-reported outcomes (PROs) for health-related quality of
life in the 2 treatment groups
• To evaluate the 2 treatment groups with respect to patient satisfaction with
the treatment
• To confirm the safety and tolerability of CAM2029 in patients with
unresectable/metastatic and well-differentiated GEP-NET
Exploratory Objectives
• To describe the effect of intensified treatment with CAM2029 in the
Open-label Extension Treatment Period
• To compare the 2 treatment groups with respect to progression-free survival 2
(PFS2) based on local Investigator assessment
• To assess hospital resource utilization
• To evaluate the 2 treatment groups with respect to treatment experience
• To evaluate the 2 treatment groups with respect to patients* impression of
disease severity
• To evaluate the 2 treatment groups with respect to Eastern Cooperative
Oncology Group (ECOG) performance status
• To assess the immunogenicity of octreotide in patients with
metastatic/inoperable and well-differentiated GEP-NET
Study design
Trial Design and Schedule
This is a prospective, multi-center, randomized, open-label, parallel-group,
Phase 3 trial comparing the efficacy of treatment with CAM2029 20 mg every 2
weeks to treatment with the Investigator*s choice of comparator, i.e.
octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks (the comparator
treatment group) in patients with advanced, well-differentiated GEP-NET.
Approximately 300 patients will be randomized to 1 of 2 treatment groups in the
Open-label Randomized Treatment Period. The patients will be followed until
disease progression and the primary PFS analysis will be performed after 194
events (i.e. disease progression) during the Randomized Treatment Period.
Patients who experience progressive disease (PD) during the Randomized
Treatment Period may enter an optional Open-label Extension Treatment Period,
during which they will be treated with CAM2029 20 mg once weekly.
After the primary PFS analysis (based on the BIRC assessment of PD), the trial
will remain open. Patients still being followed on the trial will continue as
per the schedule of assessments. Patients who are still ongoing in the
comparator treatment group at the time of the primary PFS analysis will have
the possibility to be switched to receive treatment with CAM2029 20 mg every 2
weeks, if the trial meets the primary objective.
The overall survival follow-up will end at the latest 2 years after the primary
PFS analysis. At that time, the final analysis of trial data will be conducted.
All available data from all patients up to that cut-off date will be analyzed.
A Data Monitoring Committee will be established, which will conduct periodic
reviews of safety data from the trial.
Intervention
Screening Period
The Screening Period will have a duration of up to 28 days. During this period,
eligibility will be evaluated.
Open-label Randomized Treatment Period
Eligible patients will be randomized in a 1:1 ratio to 1 of the 2 treatment
groups on Day 1:
• CAM2029 treatment group (CAM2029 20 mg, administered every 2 weeks)
• Comparator treatment group (Investigator*s choice of octreotide LAR 30 mg or
lanreotide ATG 120 mg, administered every 4 weeks)
During the Randomized Treatment Period, tumor progression will be evaluated
every 12 weeks. Safety will be evaluated continuously and plasma samples for
assessment of octreotide concentration will be taken in patients who receive
CAM2029 or octreotide LAR. Patient-reported treatment satisfaction will be
assessed using a general questionnaire and will be compared between CAM2029 and
the comparator products. Health-related quality of life parameters will also be
assessed by PROs.
Patients will continue to receive the randomized investigational medicinal
product (IMP) treatment (CAM2029/comparator) as scheduled, until they
experience any of the following:
• Disease progression as confirmed by the BIRC
• Unacceptable toxicity that precludes further treatment
• Discontinuation of treatment at the discretion of the Investigator or patient
• Lost to follow-up
• Death
If the patient discontinues the randomized IMP treatment, the patient will be
asked to return for an End-of-treatment Visit.
End-of-treatment Visit
The End-of-treatment Visit should be performed within 28 days after the date
the IMP treatment is discontinued in the Randomized Treatment Period. The
End-of-treatment Visit is not considered the end of the trial. Next-line
therapy may be started after this visit at the Investigator*s discretion.
If the patient discontinued the randomized IMP treatment due to PD, patients in
both treatment groups will have the option to start treatment with CAM2029 20
mg once weekly in an Extension Treatment Period.
Open-label Extension Treatment Period (optional)
After the BIRC confirms PD during treatment with the IMP (CAM2029/comparator)
in the Randomized Treatment Period, patients in both treatment groups may be
switched to receive treatment with CAM2029 20 mg once weekly in an Extension
Treatment Period, if the Investigator considers it beneficial for the patient.
The End-of-treatment Visit may be the same visit as the first visit in the
Extension Treatment Period. During this period, tumor progression will be
evaluated every 12 weeks. Safety will be evaluated continuously and plasma
samples for assessment of octreotide concentration will be taken.
Patient-reported treatment satisfaction will be assessed using a general
questionnaire and health-related quality of life parameters will be assessed by
PROs.
Treatment with CAM2029 will continue until the patients experience any of the
following:
• Disease progression as confirmed by the BIRC
• Unacceptable toxicity that precludes further treatment
• Discontinuation of treatment at the discretion of the Investigator or patient
• Lost to follow-up
• Death
After discontinuation of the CAM2029 once-weekly treatment, the patient will be
asked to return for an End-of-extension-treatment Visit.
End-of-extension-treatment Visit
The End-of-extension-treatment Visit should be performed within 28 days after
the date the CAM2029 treatment is discontinued in the Extension Treatment
Period. The End-of-extension-treatment Visit is not considered the end of the
trial. Next-line therapy may be started after this visit at the Investigator*s
discretion.
After end of treatment: safety follow-up, efficacy follow-up and survival
follow-up
Study burden and risks
- The risks associated with the study medications CAM2029, Octreotide LAR and
Lanreotide ATG
- The discomforts linked to the procedures, such as blood draws, CT scans (adn
contrast used), MRI (and constrast used), PET-CT scan, ECG, bone scan
- The burden of additional visits to the study center, additional procedures
and questionnaires
These risks are included in the patient information sheet, and in the section
additional remarks of this form
Ideon Science Park SE-223 70 Lund
Lund SE-223 70
SE
Ideon Science Park SE-223 70 Lund
Lund SE-223 70
SE
Listed location countries
Age
Inclusion criteria
Main Inclusion Criteria for the Trial
• 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
Main Inclusion Criteria for the Extension Treatment Period
• Disease progression confirmed by the BIRC
• At least 6 months of treatment with IMP (CAM2029/comparator) in the
Randomized Treatment Period before documented disease progression
Exclusion criteria
Main Exclusion Criteria for the Trial
• 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
Main Exclusion Criteria for the Extension Treatment Period
• Unresolved, drug-related serious adverse event that, in the Investigator's
opinion, contraindicates treatment with CAM2029
• Clinically significant symptoms, medical conditions, rapid clinical
deterioration, or other circumstances that, in the Investigator's opinion,
would preclude compliance with the protocol, adequate cooperation in the trial,
or may prevent the patient from safely participating in the trial
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508723-12-00 |
| EudraCT | EUCTR2021-000849-40-NL |
| CCMO | NL78414.031.21 |