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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy

NCTNCT00363051 (opens ClinicalTrials.gov in a new tab)Other idCRAD001C2239
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 2
Enrollment
160 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
11 countries

United States, Argentina, Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, Sweden

Start
Jun 2006
Primary completion
Jan 2008
Completion
Apr 2012
First posted
15 Aug 2006 (estimated)
Last update posted
10 May 2013 (estimated)
Conditions
Islet Cell Carcinoma · Neuroendocrine Carcinoma · Neuroendocrine Tumor · Pancreatic Neoplasms

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2006200820102012
  1. Ph 2

    Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy

    NCT00363051

    Jun 2006 to Apr 2012

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study was to assess the efficacy and safety of everolimus in the treatment of advanced pancreatic neuroendocrine tumor (NET) not responsive to cytotoxic chemotherapy. All patients were treated with everolimus until either tumor progression was documented using a standard criteria that measures tumor size called Response Evaluation Criteria in Solid tumors (RECIST), or until unacceptable toxicity occurred, or until the patient or investigator requested discontinuation of treatment.

Interventions

  • Everolimus 10 mgDrug
  • Octreotide DepotDrug

Arms1

  • Experimental

    Everolimus 10 mg

    Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Stratum 2 patients who were to receive everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot therapy. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)

    Time frame · from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)

    Registry description

    Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

Secondary outcomes(11)

  1. Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review

    Time frame · from date of first documented confirmed response to time to progression, at least 3 months

    Registry description

    Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR): * Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. * Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression. Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions

  2. Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review

    Time frame · from date of first documented confirmed response to time to progression, at least 3 months

    Registry description

    Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR): * Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. * Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression. Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions

  3. Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)

    Time frame · from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months)

    Registry description

    Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

  4. Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1]

    Time frame · on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

    Registry description

    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

  5. Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2]

    Time frame · on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

    Registry description

    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

  6. Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1)

    Time frame · from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

    Registry description

    Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was constructed. Median PFS was obtained and displayed along with 95% confidence intervals.

  7. Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2)

    Time frame · from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

    Registry description

    Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was constructed. Median PFS was obtained and displayed along with 95% confidence intervals.

  8. Time to Overall Survival (OS)(Stratum 1)

    Time frame · from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012

    Registry description

    Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.

  9. Time to Overall Survival (OS) (Stratum 2)

    Time frame · from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012

    Registry description

    Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.

  10. Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2)

    Time frame · Cycle 1 Day 15

    Registry description

    For all patients in both strata, a blood sample for everolimus trough level determination will be collected immediately prior to the everolimus administration on Cycle 1 Day 15, Cycle 2 Day 1, and every month thereafter. A treatment cycle was defined as 28 days of consecutive daily treatment with everolimus and treatment continued until tumor progression. It is critical that patients not take their daily everolimus dose before the sample is drawn.

  11. Effect of Octreotide Depot on the Trough Concentrations of Everolimus

    Time frame · Cycle 1 Day 1, Cycle 2 Day 1

    Registry description

    The effect of Octreotide Depot on the trough concentrations of everolimus was assessed at Cycle 1 Day 15.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)

Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)

GroupValue (percentage of participants)
Stratum 1: Everolimus 10 mg9.6
Secondary and other outcome results(7)
Secondary outcomeMedian· from date of first documented confirmed response to time to progression, at least 3 months

Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review

GroupValue (Months)
Stratum 1: Everolimus 10 mg10.64
Secondary outcome· from date of first documented confirmed response to time to progression, at least 3 months

Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review

GroupValue
Stratum 2: Everolimus 10 mg + Octreotide Depotnot posted
Secondary outcomeNumber· from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months)

Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)

GroupValue (percentage of participants)
Stratum 2: Everolimus 10 mg + Octreotide Depot4.4
Secondary outcomeNumber· on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1]

GroupValue (Participants)
Stratum 1: Everolimus 10 mg115
Secondary outcomeNumber· on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2]

GroupValue (Participants)
Stratum 2: Everolimus 10 mg + Octreotide Depot45
Secondary outcomeMedian· from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1)

GroupValue (Months)
Stratum 1: Everolimus 10 mg9.69
Secondary outcomeMedian· from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2)

GroupValue (Months)
Stratum 2: Everolimus 10 mg + Octreotide Depot16.69

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Stratum 1: Everolimus 10 mgStratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.–63 / 115115 / 115
Stratum 2: Everolimus 10 mg + Octreotide DepotStratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.–27 / 4544 / 45

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion criteria for both strata: * Advanced (unresectable or metastatic) biopsy-proven pancreatic Neuroendocrine tumor (NET) * Confirmed low-grade or intermediate-grade neuroendocrine carcinoma * Objective disease progression by Response Evaluation Criteria in Solid tumors (RECIST) criteria while receiving cytotoxic chemotherapy or at any time after receiving an adequate course of cytotoxic chemotherapy (i.e., at least 3 consecutive cycles or months of treatment with the same cytotoxic drug or regimen) * Presence of at least one measurable disease using RECIST criteria at screening (computer tomography \[CT\] or Magnetic resonance imaging \[MRI\]) * Adequate bone marrow, liver and kidney function * WHO Performance Status 0-2. Inclusion criteria for Stratum 2 only: * Meet all inclusion criteria defined above for both strata. * Receiving treatment (at least 3 consecutive months) with Octreotide Depot. * In addition to documentation of progressive disease on or after chemotherapy, patients in stratum 2 must have documented objective progression of disease while receiving Octreotide Depot. Exclusion criteria for both strata: * Anticancer therapy within 3 weeks of enrollment. * Patients with poorly differentiated neuroendocrine carcinoma * Hepatic artery embolization within the last 6 months * Prior therapy with everolimus or other rapamycins (sirolimus, temsirolimus) * Other concurrent malignancy * Other serious intercurrent infections or nonmalignant uncontrolled medical illnesses Exclusion Criterion for Stratum 1 only: • Received treatment with Octreotide Depot or any other long-acting somatostatin analogue in the 60 days prior to enrollment or any short-acting somatostatin analogue in the two weeks prior to enrollment. Other protocol-defined inclusion/exclusion criteria applied.

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