Neoplasms

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Melanoma

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Carcinoma, Merkel Cell

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Merkel Cell Carcinoma

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All Drugs and Chemicals

Pasireotide

Somatostatin

Hormones

Hormone Antagonists

Pasireotide, will be administered to all patients by s.c. injection, beginning with a dose of 300 μg administered three times daily (t.i.d.) for 2 weeks. If no pasireotide-related clinically meaningful/uncontrolled grade 3 or grade 4 adverse events occur the dose will be administered to all patients at an increased dose of 600 μg t.i.d. for 2 weeks, followed by 2 weeks of 900 μg t.i.d. and followed by 2 weeks of 1200 μg t.i.d. After the 8 weeks period, patients will be kept on treatment drug (highest dose without clinically meaningful/uncontrolled AEs), switched to the corresponding pasireotide LAR dose and followed up for an extra 6 months.

At the start of the follow-up phase patients will be switched to pasireotide LAR administered intramuscularly every 28 days by using the following conversion algorithm so that the steady state PK exposure (Cmax and Ctrough) of pasireotide will be maintained: 300 μg s.c. t.i.d. fi 20mg LAR i.m. q 28 days 600 μg s.c. t.i.d. fi 40 mg LAR i.m. q 28 days 900 μg s.c. t.i.d. fi 60 mg LAR i.m. q 28 days 1200 μg s.c. t.id. fi 80 mg LAR i.m. q 28 days In addition, all patients will keep the treatment with pasireotide s.c. during the first 2 weeks of the LAR phase. The use of s.c. dosing during the initial 2 week period following the first LAR dose provides an appropriate level of medication during the LAR nadir.

Pasireotide, will be administered to all patients by s.c. injection, beginning with a dose of 300 μg administered three times daily (t.i.d.) for 2 weeks. If no pasireotide-related clinically meaningful/uncontrolled grade 3 or grade 4 adverse events occur the dose will be administered to all patients at an increased dose of 600 μg t.i.d. for 2 weeks, followed by 2 weeks of 900 μg t.i.d. and followed by 2 weeks of 1200 μg t.i.d. After the 8 weeks period, patients will be kept on treatment drug (highest dose without clinically meaningful/uncontrolled AEs) , switched to the corresponding pasireotide LAR dose and followed up for an extra 6 months.

Pasireotide sub-cutaneous formulation

Pasireotide lon acting release formulation

Novartis Pharmaceuticals

This study will evaluate the preliminary safety, pharmacokinetics, and anti-tumor activity of pasireotide s.c. in patients with metastatic melanoma or metastatic Merkel cell carcinoma. The study consists of three phases: screening, intra-patient dose-escalation, and follow-up phases.

In the screening phase patient will be informed of all aspects of the study and sign informed consent forms and then be screened for study eligibility.

During the intra-patient dose escalation phase, 18 patients will be treated with pasireotide s.c. 300 μg t.i.d. for 2 weeks. If there are no unacceptable AEs, defined as drug-related clinically meaningful, uncontrolled grade 3 or any grade 4 toxicities, patients will be dose escalated to 600 μg t.i.d. for 2 more weeks, then 900 μg t.i.d. for 2 weeks and then 1200 μg for 2 weeks provided that there are no unacceptable AEs. Each patient will be in the dose escalation phase for a maximum of 8 weeks.

At end of the intra-patient dose escalation phase, patients will be allowed to switch to 80 mg pasireotide LAR i.m. q 28 d (or a lower dose in case of toxicity) for an additional 6 months or until disease progression, or unacceptable AEs, or patient withdraws consent. In addition, all patients will keep their pasireotide s.c. t.i.d. treatment (same dose as that at the end of the 8-week dose escalation phase) during the first 2 weeks of the LAR follow-up phase, except on the day receiving the first LAR dose because of an anticipated initial burst of drug release.

A Phase I, Exploratory, Intra-patient Dose Escalation Study to Investigate the Preliminary Safety, Pharmacokinetics, and Anti-tumor Activity of Pasireotide (SOM230) s.c.Followed by Pasireotide LAR in Patients With Metastaticmelanoma or Metastatic Merkel Cell Carcinoma

Number of patients with AEs (overall and by severity) SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with laboratory abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with ECG according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with vital sign abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Tumor response as measured by DCR defined as the proportion of patients with best overall response of complete response (CR), partial response (PR) or stable response (SR) according to the RECIST Version 1.0 Criteria.

Pasireotide plasma concentrations will be summarized by dose and time and PK profile of pasireotide concentration over time will be generated by dose.

Melanoma response biomarkers (MIA, S100B) will be evaluated in pre- and post-treatment samples on all patients to assess the biochemical response to pasireotide as change from baseline at Day 8, 15, 22, 29, 36, 43, 50, 57, 113, 169 and 225.

PD and cellular effect makers in tumor Protein expression levels for different PD markers such as p4EBP-1, pS6, pAKT, pERK and for different cellular effect markers of proliferation and apoptosis (such as Ki67, cyclin D1, cleaved caspase, PARP), angiogenesis (such as microvessel density) and secretion (such as IGF-1 receptor); change from baseline of these markers at day 29 and 57.

Number of patients with AEs (overall and by severity) SAEs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Number of patients with ECG abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Number of patients with laboratory abnormalities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Number of patients with vital sign abnormalities and changes in vital signs according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Spots Global Cancer Trial Database for metastatic melanoma and merkel cell carcinoma