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

NCT ID: NCT01625520

Last Updated: 2016-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29

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.

Conditions

Medullary Thyroid Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SOM230 alone or in combination with RAD001.

Intervention Type: DRUG

SOM230 (pasireotide) 60 mg i.m. injection once every 28 days, +/- 2 days. RAD001 (everolimus) 10 mg per os daily.

Interventions

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.

Intervention Type: DRUG

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,
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Responsible Party

Annamaria Colao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Annamaria Colao

Role: PRINCIPAL_INVESTIGATOR

"Federico II" University of Naples, Italy

Locations

Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples

Naples, Italy, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 29572709 (View on PubMed)

Other Identifiers

2010-023128-26

Identifier Type: -

Identifier Source: org_study_id