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SOM230 Alone or in Combination With RAD001 in Patients With Medullary Thyroid Cancer

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ClinicalTrials.gov Identifier: NCT01625520
Recruitment Status : Completed
First Posted : June 21, 2012
Last Update Posted : April 25, 2016
Sponsor:
Information provided by (Responsible Party):
Annamaria Colao, Federico II University

Tracking Information
First Submitted Date  ICMJE May 25, 2012
First Posted Date  ICMJE June 21, 2012
Last Update Posted Date April 25, 2016
Study Start Date  ICMJE February 2012
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2012)
Efficacy of SOM230 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer [ 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. ]
Efficacy is defined as progression-free survival (PFS), according to RECIST criteria, in patients treated with SOM230.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2012)
  • Efficacy of SOM230 in combination with RAD001 in patients with progressive metastatic or postoperative persistent medullary thyroid cancer. [ 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. ]
    Efficacy is defined as progression-free survival (PFS), according to RECIST criteria, in patients treated with SOM230 in combination with RAD001.
  • Biochemical response [ Time Frame: From date of start therapy, 1 month, 2 month, 3 month, 6 month time point evaluation, up to 6 months. ]
    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 [ Time Frame: From date of start therapy, 3 month, 6 month time point evaluation, up to 6 months. ]
    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 Frame: From date of start therapy to the end of the study or death from any cause, whichever came first, up to 6 months. ]
  • Time to response [ Time Frame: From date of start therapy, 3 month, 6 month time point evaluation, up to 6 months. ]
    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 [ Time Frame: From time of response to time of tumor progression or death from any cause, whichever came first. ]
    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 [ Time Frame: From date of start therapy until the end of the study, every 30 days, up to 6 months. ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SOM230 Alone or in Combination With RAD001 in Patients With Medullary Thyroid Cancer
Official Title  ICMJE Mono Centre, Open Label Proof of Concept Study SOM230 in Progressive Medullary Thyroid Cancer Patients and the Combination With RAD001 Upon Progression
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Medullary Thyroid Cancer
Intervention  ICMJE Drug: SOM230 alone or in combination with RAD001.
SOM230 (pasireotide) 60 mg i.m. injection once every 28 days, +/- 2 days. RAD001 (everolimus) 10 mg per os daily.
Study Arms  ICMJE Experimental: SOM230 alone or in combination with RAD001
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: Drug: SOM230 alone or in combination with RAD001.
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 20, 2012)
19
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01625520
Other Study ID Numbers  ICMJE 2010-023128-26
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Annamaria Colao, Federico II University
Study Sponsor  ICMJE Federico II University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Annamaria Colao "Federico II" University of Naples, Italy
PRS Account Federico II University
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP