Back to resultsSOM230 Alone or in Combination With RAD001 in Patients With Medullary Thyroid Cancer
Primary Purpose
Medullary Thyroid Cancer
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
SOM230 alone or in combination with RAD001.
Sponsored by
About this trial
This is an interventional treatment trial for Medullary Thyroid Cancer focused on measuring Progressive metastatic, postoperative persistent
Eligibility Criteria
Inclusion Criteria:
- Patients with progressive metastatic or postoperative persistent medullary thyroid cancer who have histopathologically confirmed disease and measurable tumor lesions. (Postoperative persistent after surgical removal is characterized by increased levels of calcitonin with or without radiological detectable tumour relapse or metastases.)
- Patients with evidence of biochemical progression of disease, as expressed by progressive increase of serum calcitonin levels, assessed once a month for at least three months before study entry, according to RECIST definitions (elevation of the markers for at least 25 %).
- Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.
- Adequate organ function - Karnofsky-Index performance status >60%
- Life expectancy > 6 months
- Age > 18 years
- Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization and a urine pregnancy test 48 hours prior to the administration of the first study treatment.
- Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
- Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to enrolment.
Exclusion Criteria:
- Unstable systemic diseases including uncontrolled hypertension, active uncontrolled infections, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
- Known hypersensitivity to somatostatin analogues.
- Pregnant or breast-feeding patients
- Sign of recurrence of prior or concomitant malignancies (within the last 3 years or requiring active treatment) other than MTC; with the exception of previous basal cell skin cancer, previous cervical carcinoma in situ
- Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus)
- Participation in a clinical trial to test an investigational drug within 4 weeks prior to visit 1.
- Any of severe and/or uncontrolled medical conditions:
- Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment,
- QT related exclusion criteria
- Previous treatments with chemotherapy, loco regional therapy (eg, chemoembolization) or interferon are permitted providing that toxicity has resolved to < Grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.
Sites / Locations
- Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SOM230 alone or in combination with RAD001
Arm Description
Patients with progressive metastatic or postoperative persistent medullary thyroid cancer will start the study treatment as a mono therapy with SOM230. Patients benefiting from the treatment will continue with the monotherapy (stable disease or better according to RECIST). Patients progressing will be switched to the combination therapy with SOM230 and RAD001.
Outcomes
Primary Outcome Measures
Efficacy of SOM230 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer
Efficacy is defined as progression-free survival (PFS), according to RECIST criteria, in patients treated with SOM230.
Secondary Outcome Measures
Efficacy of SOM230 in combination with RAD001 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer.
Efficacy is defined as progression-free survival (PFS), according to RECIST criteria, in patients treated with SOM230 in combination with RAD001.
Biochemical response
Biochemical response is defined as the change of calcitonin and carcinoembryonic antigen (CEA) serum concentrations recorded from date of study entry until disease progression compared to baseline. Time-to-biochemical-response is defined as the time from start of the study treatment to first documentation of biochemical response of calcitonin and CEA concentrations, respectively. Duration of biochemical response is defined as the time from the first documentation of biochemical response to the first documentation of biochemical progression or to death due to any cause, whichever occurs first.
Objective tumor response
Objective tumor response (OR) are the overall responses recorded from date of study entry until end of study/study exclusion, according to RECIST definitions, confirmed by repeat measurements. OR includes complete remission (CR), partial (PR), stable disease (SD) and progressive disease (PD) of all measurable tumor lesions of all evaluable patients.
Overall survival
Time to response
Time to response is defined as the time from start of treatment to the first objective tumor response (PR or CR) observed. Patients who did not achieve a confirmed PR or CR will be censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease)
Duration of response
Duration of response is defined as the time from onset of response (CR/PR) to objective tumor progression or death from any cause. Patients not experiencing progression or death will be censored with the date of their last adequate tumor assessment.
Safety
Safety will be evaluated using assessment of adverse events and laboratory data. The assessment of safety will be based on the frequency of adverse events and on the number of laboratory values that are new or worsening based on the common toxicity criteria (CTC) grade. Other safety data (e.g. vital signs) will be considered appropriately.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01625520
Brief Title
SOM230 Alone or in Combination With RAD001 in Patients With Medullary Thyroid Cancer
Official Title
Mono Centre, Open Label Proof of Concept Study SOM230 in Progressive Medullary Thyroid Cancer Patients and the Combination With RAD001 Upon Progression
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Federico II University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A mono centre study to evaluate the efficacy of SOM230 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer.
Detailed Description
Medullary thyroid cancer (MTC) is a neuroendocrine tumor originating from thyroid C cells. Neuroendocrine tumors have been demonstrated to express somatostatin receptors as well as mTOR pathway. The somatostatin analogues now available (octreotide and lanreotide) act preferentially through the somatostatin receptor subtype 2 (sst2). In MTC, these compounds have been reported to exert anti-secretive effects on calcitonin but no anti-proliferative effects.SOM230 (pasireotide) is a new somatostatin analogue showing a peculiar binding profile with high affinity for sst1, sst2, sst3, sst5. Preliminary data show SOM230 to be effective in a phase II study on patients with metastatic carcinoid. RAD001 (everolimus) is a novel agent that interacts with mTOR. It was demonstrated to inhibit tumor growth in neuroendocrine tumor cell lines. Some clinical trials have explored the efficacy of a combined therapy with RAD001 plus octreotide in patients with digestive neuroendocrine tumors, highlighting encouraging results in term of tumor control.In particular, octreotide and RAD001 seem to show a synergistic activity in inhibiting neuroendocrine tumor proliferation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medullary Thyroid Cancer
Keywords
Progressive metastatic, postoperative persistent
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SOM230 alone or in combination with RAD001
Arm Type
Experimental
Arm Description
Patients with progressive metastatic or postoperative persistent medullary thyroid cancer will start the study treatment as a mono therapy with SOM230. Patients benefiting from the treatment will continue with the monotherapy (stable disease or better according to RECIST). Patients progressing will be switched to the combination therapy with SOM230 and RAD001.
Intervention Type
Drug
Intervention Name(s)
SOM230 alone or in combination with RAD001.
Intervention Description
SOM230 (pasireotide) 60 mg i.m. injection once every 28 days, +/- 2 days. RAD001 (everolimus) 10 mg per os daily.
Primary Outcome Measure Information:
Title
Efficacy of SOM230 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer
Description
Efficacy is defined as progression-free survival (PFS), according to RECIST criteria, in patients treated with SOM230.
Time Frame
From date of start therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Secondary Outcome Measure Information:
Title
Efficacy of SOM230 in combination with RAD001 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer.
Description
Efficacy is defined as progression-free survival (PFS), according to RECIST criteria, in patients treated with SOM230 in combination with RAD001.
Time Frame
From date of start therapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Title
Biochemical response
Description
Biochemical response is defined as the change of calcitonin and carcinoembryonic antigen (CEA) serum concentrations recorded from date of study entry until disease progression compared to baseline. Time-to-biochemical-response is defined as the time from start of the study treatment to first documentation of biochemical response of calcitonin and CEA concentrations, respectively. Duration of biochemical response is defined as the time from the first documentation of biochemical response to the first documentation of biochemical progression or to death due to any cause, whichever occurs first.
Time Frame
From date of start therapy, 1 month, 2 month, 3 month, 6 month time point evaluation, up to 6 months.
Title
Objective tumor response
Description
Objective tumor response (OR) are the overall responses recorded from date of study entry until end of study/study exclusion, according to RECIST definitions, confirmed by repeat measurements. OR includes complete remission (CR), partial (PR), stable disease (SD) and progressive disease (PD) of all measurable tumor lesions of all evaluable patients.
Time Frame
From date of start therapy, 3 month, 6 month time point evaluation, up to 6 months.
Title
Overall survival
Time Frame
From date of start therapy to the end of the study or death from any cause, whichever came first, up to 6 months.
Title
Time to response
Description
Time to response is defined as the time from start of treatment to the first objective tumor response (PR or CR) observed. Patients who did not achieve a confirmed PR or CR will be censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease)
Time Frame
From date of start therapy, 3 month, 6 month time point evaluation, up to 6 months.
Title
Duration of response
Description
Duration of response is defined as the time from onset of response (CR/PR) to objective tumor progression or death from any cause. Patients not experiencing progression or death will be censored with the date of their last adequate tumor assessment.
Time Frame
From time of response to time of tumor progression or death from any cause, whichever came first.
Title
Safety
Description
Safety will be evaluated using assessment of adverse events and laboratory data. The assessment of safety will be based on the frequency of adverse events and on the number of laboratory values that are new or worsening based on the common toxicity criteria (CTC) grade. Other safety data (e.g. vital signs) will be considered appropriately.
Time Frame
From date of start therapy until the end of the study, every 30 days, up to 6 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with progressive metastatic or postoperative persistent medullary thyroid cancer who have histopathologically confirmed disease and measurable tumor lesions. (Postoperative persistent after surgical removal is characterized by increased levels of calcitonin with or without radiological detectable tumour relapse or metastases.)
Patients with evidence of biochemical progression of disease, as expressed by progressive increase of serum calcitonin levels, assessed once a month for at least three months before study entry, according to RECIST definitions (elevation of the markers for at least 25 %).
Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.
Adequate organ function - Karnofsky-Index performance status >60%
Life expectancy > 6 months
Age > 18 years
Women of childbearing potential must have a negative serum pregnancy test within 14 days of randomization and a urine pregnancy test 48 hours prior to the administration of the first study treatment.
Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.
Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to enrolment.
Exclusion Criteria:
Unstable systemic diseases including uncontrolled hypertension, active uncontrolled infections, psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Known hypersensitivity to somatostatin analogues.
Pregnant or breast-feeding patients
Sign of recurrence of prior or concomitant malignancies (within the last 3 years or requiring active treatment) other than MTC; with the exception of previous basal cell skin cancer, previous cervical carcinoma in situ
Prior therapy with mTOR inhibitors (e.g. sirolimus, temsirolimus, everolimus)
Participation in a clinical trial to test an investigational drug within 4 weeks prior to visit 1.
Any of severe and/or uncontrolled medical conditions:
Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment,
QT related exclusion criteria
Previous treatments with chemotherapy, loco regional therapy (eg, chemoembolization) or interferon are permitted providing that toxicity has resolved to < Grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annamaria Colao
Organizational Affiliation
"Federico II" University of Naples, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples
City
Naples
ZIP/Postal Code
80131
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
29572709
Citation
Faggiano A, Modica R, Severino R, Camera L, Fonti R, Del Prete M, Chiofalo MG, Aria M, Ferolla P, Vitale G, Pezzullo L, Colao A. The antiproliferative effect of pasireotide LAR alone and in combination with everolimus in patients with medullary thyroid cancer: a single-center, open-label, phase II, proof-of-concept study. Endocrine. 2018 Oct;62(1):46-56. doi: 10.1007/s12020-018-1583-7. Epub 2018 Mar 23.
Results Reference
derived
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SOM230 Alone or in Combination With RAD001 in Patients With Medullary Thyroid Cancer
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