Trial Title:
Everolimus 5 mg vs 10 mg/Daily for Patients With Neuroendocrine Tumors
NCT ID:
NCT06472388
Condition:
Neuroendocrine Tumors
Progression
Neuroendocrine Tumor Grade 1
Neuroendocrine Tumor Grade 2
Neuroendocrine Tumor of Pancreas
Neuroendocrine Tumor of the Lung
Neuroendocrine Tumor Carcinoid
Conditions: Official terms:
Neoplasms
Neuroendocrine Tumors
Carcinoid Tumor
Pancreatic Neoplasms
Lung Neoplasms
Everolimus
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized, open-label, phase II near-equivalence clinical trial of oral everolimus 5 mg
vs 10 mg oral/daily and continuously in patients with Grade 1 or Grade 2 metastatic NET,
with tumor progression or intolerance to at least one line of treatment and with
radiological disease progression within 6 months.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Everolimus 5 MG
Description:
oral everolimus 5 mg/daily
Arm group label:
Everolimus 10
Arm group label:
Everolimus 5
Summary:
Everolimus is approved in many countries to treat patients with advanced/metastatic
well-differentiated neuroendocrine tumors (NET), providing median progression-free
survival times of approximately 12 months across different types of NET. However, it is
can cause severe adverse effects. Phase I trial demonstrated that a dose of 5mg/day/week
was sufficient to inhibit cell proliferation by blocking the mTOR pathway.
This is a randomized, open-label, phase II near-equivalence clinical trial of oral
everolimus 5 mg vs 10 mg oral/daily and continuously in patients with Grade 1 or Grade 2
metastatic NET, with tumor progression or intolerance to at least one line of treatment
and with radiological disease progression within 6 months.
Detailed description:
Everolimus toxicity can also be serious, requiring hospital medical assistance. In a
study with more than 100 Latin American patients led by our group, approximately 20% of
patients with NET treated with everolimus 10mg/day had serious infections, such as
pneumonia, abscesses, pyelonephritis, with 7% developing opportunistic infections, such
as toxoplasmosis and pneumocystosis, requiring hospital admissions.
The rationale for testing 5mg/day comes from the results of phase I trials of everolimus,
where a dose of 5mg/day was sufficient to inhibit cell proliferation by blocking the mTOR
pathway.
Therefore, everolimus 5mg/day appears to have antitumor effects equivalent to 10mg/day,
but it is less toxic than 10mg/day. Retrospective data from our center also suggest that
5mg is similar to 10mg/daily in terms of time to treatment failure in patients with
advanced NETs (unpublished data).
Objectives:
- To evaluate whether everolimus at a dose of 5 mg/day may be as effective, but safer,
as 10 mg/day in the treatment of patients with advanced NET.
- To compare progression-free survival and time to treatment failure between study
arms
- To compare radiological response using RECIST v.1.1 criteria.
- To compare the frequency of grade > 1 toxicities using CTCAE v.5.0.
- To assess tolerability by measuring the frequency and intensity of adverse events
measured by the CTCAE version 5.0 criteria and the need for temporary or permanent
interruption of everolimus.
Methods:
Randomized, open-label, phase II near-equivalence clinical trial of oral everolimus 5 mg
vs 10 mg oral/daily and continuously in patients with Grade 1 or Grade 2 metastatic NET,
with tumor progression or intolerance to at least one line of treatment and with
radiological disease progression within 6 months.
Eligibility criteria:
Inclusion:
- Histological confirmation of well-differentiated Grade 1/Grade 2 NET from
gastrointestinal, pancreatic, pulmonary or unknown primary sites.
- Metastatic or locally advanced and unresectable disease, measurable by images
- Disease progression by RECIST 1.1 in the last 6 months assessed by local
investigators
- At least one previous line of systemic treatment (suspended for more than 3 weeks).
- Eastern Cooperative Oncology Group (ECOG) 0-2
- Good organ function:
- Hemoglobin > 8 g/dL
- Neutrophils ≥ 1,500/mm³
- Platelets > 90,000/mm³
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN
[upper limit of normal] or ≤ 5 x ULN for patients with liver metastases
- Bilirubin ≤ 1.5 x ULN, creatinine < 1.5 mg/dL
Concomitant use of somatostatin analogues is allowed for patients with functioning NET.
Exclusion:
- Aggressive disease requiring cytotoxic therapy
- Severe/uncontrolled comorbid conditions that deem participant unfit for everolimus
therapy, as per investigators' judgement.
- MiNEN
Procedures:
Randomization 1:1 will be performed centrally by RedCap software at AC Camargo Cancer
Center, Sao Paulo, Brasil.
- Group 5 mg: participants will receive everolimus at a dose of 5 mg, orally, per day,
continuously
- Group 10 mg group: participants will receive everolimus at a dose of 10 mg, orally,
per day, continuously
The participant will receive everolimus 5mg or 10mg and must take 1 (one) tablet, orally,
once a day, after breakfast, starting within 4 weeks from randomization. Every 4 weeks of
treatment will correspond to 1 treatment cycle. Before starting each cycle, participants
will undergo a medical visit to evaluate undesirable effects, medical history, physical
examination and check the results of blood tests.
CT scans (or MRI, if applicable) will be performed at every 3 cycles to assess treatment
antitumor effect until progression. The treatment will last until tumor progression by
RECIST 1.1, intolerance/ severe adverse effects or consent withdrawal.
Participants will be evaluated clinically and with laboratory tests every 4 weeks until
resolution of any adverse effects of the treatment. Patients who receive at least one
dose of everolimus will be evaluated for the occurrence of toxicities
Sample size:
N=100 patients (50 per arm)
H0= 50% progression free at 12 months H1= 42% progression free at 12 months (inferior
value of the 95% CI, based on RADIANT trials) Alpha error (one-sided) = 5% Beta error =
10% Attrition rate = 20%
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histological confirmation of well-differentiated Grade 1/Grade 2 NET from
gastrointestinal, pancreatic, pulmonary or unknown primary sites.
- Metastatic or locally advanced and unresectable disease, measurable by images
- Disease progression by RECIST 1.1 in the last 6 months assessed by local
investigators
- At least one previous line of systemic treatment (suspended for more than 3 weeks).
- Eastern Cooperative Oncology Group (ECOG) 0-2 o Good organ function:
- Hemoglobin > 8 g/dL
- Neutrophils ≥ 1,500/mm³
- Platelets > 90,000/mm³
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN
[upper limit of normal] or ≤ 5 x ULN for patients with liver metastases
- Bilirubin ≤ 1.5 x ULN, creatinine < 1.5 mg/dL
Exclusion Criteria:
- Aggressive disease requiring cytotoxic therapy
- Severe/uncontrolled comorbid conditions that deem participant unfit for everolimus
therapy, as per investigators' judgement.
- MiNEN
Gender:
All
Minimum age:
16 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
AC Camargo Cancer Center
Address:
City:
São Paulo
Zip:
01509010
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Rachel P Riechelmann, MD
Phone:
+5521895000
Phone ext:
2776
Email:
rachel.riechelmann@accamargo.org.br
Facility:
Name:
AC Camargo Cancer Center
Address:
City:
Sao Paulo
Zip:
01509010
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Rachel P Riechelmann, MD
Email:
rachel.riechelmann@accamargo.org.br
Start date:
April 24, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
AC Camargo Cancer Center
Agency class:
Other
Source:
AC Camargo Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06472388
