Ignite Creation Date:
2024-07-17 @ 11:36 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06472388
Status:
RECRUITING
Last Update Posted:
2024-06-25
First Post:
2024-05-03
Brief Title:
Everolimus 5 mg vs 10 mgDaily for Patients With Neuroendocrine Tumors
Sponsor:
AC Camargo Cancer Center
Organization:
AC Camargo Cancer Center
Study Overview
Official Title:
Randomized Phase II Trial of Everolimus 5 mg vs 10 mgDaily for Patients With Advanced Neuroendocrine Tumors
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EVENET
Brief Summary:
Everolimus is approved in many countries to treat patients with advancedmetastatic 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 5mgdayweek 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 oraldaily 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
This is a randomized open-label phase II near-equivalence clinical trial of oral everolimus 5 mg vs 10 mg oraldaily 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 10mgday 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 5mgday comes from the results of phase I trials of everolimus where a dose of 5mgday was sufficient to inhibit cell proliferation by blocking the mTOR pathway
Therefore everolimus 5mgday appears to have antitumor effects equivalent to 10mgday but it is less toxic than 10mgday Retrospective data from our center also suggest that 5mg is similar to 10mgdaily in terms of time to treatment failure in patients with advanced NETs unpublished data
Objectives
To evaluate whether everolimus at a dose of 5 mgday may be as effective but safer as 10 mgday 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 v11 criteria
To compare the frequency of grade 1 toxicities using CTCAE v50
To assess tolerability by measuring the frequency and intensity of adverse events measured by the CTCAE version 50 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 oraldaily 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 1Grade 2 NET from gastrointestinal pancreatic pulmonary or unknown primary sites
Metastatic or locally advanced and unresectable disease measurable by images
Disease progression by RECIST 11 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 gdL
Neutrophils 1500mm³
Platelets 90000mm³
Aspartate aminotransferase AST and Alanine aminotransferase ALT 25 x ULN upper limit of normal or 5 x ULN for patients with liver metastases
Bilirubin 15 x ULN creatinine 15 mgdL
Concomitant use of somatostatin analogues is allowed for patients with functioning NET
Exclusion
Aggressive disease requiring cytotoxic therapy
Severeuncontrolled comorbid conditions that deem participant unfit for everolimus therapy as per investigators judgement
MiNEN
Procedures
Randomization 11 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 11 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
N100 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
The rationale for testing 5mgday comes from the results of phase I trials of everolimus where a dose of 5mgday was sufficient to inhibit cell proliferation by blocking the mTOR pathway
Therefore everolimus 5mgday appears to have antitumor effects equivalent to 10mgday but it is less toxic than 10mgday Retrospective data from our center also suggest that 5mg is similar to 10mgdaily in terms of time to treatment failure in patients with advanced NETs unpublished data
Objectives
To evaluate whether everolimus at a dose of 5 mgday may be as effective but safer as 10 mgday 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 v11 criteria
To compare the frequency of grade 1 toxicities using CTCAE v50
To assess tolerability by measuring the frequency and intensity of adverse events measured by the CTCAE version 50 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 oraldaily 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 1Grade 2 NET from gastrointestinal pancreatic pulmonary or unknown primary sites
Metastatic or locally advanced and unresectable disease measurable by images
Disease progression by RECIST 11 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 gdL
Neutrophils 1500mm³
Platelets 90000mm³
Aspartate aminotransferase AST and Alanine aminotransferase ALT 25 x ULN upper limit of normal or 5 x ULN for patients with liver metastases
Bilirubin 15 x ULN creatinine 15 mgdL
Concomitant use of somatostatin analogues is allowed for patients with functioning NET
Exclusion
Aggressive disease requiring cytotoxic therapy
Severeuncontrolled comorbid conditions that deem participant unfit for everolimus therapy as per investigators judgement
MiNEN
Procedures
Randomization 11 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 11 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
N100 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None