Phase II Study of Subcutaneous Inj. Depot of Octreotide in Patients With Acromegaly and Neuroendocrine Tumours (NETs)

A Phase II, Open-label, Multicentre, Randomised Study of the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of CAM2029 in Patients With Acromegaly and Neuroendocrine Tumours (NETs) Previously Treated With Sandostatin® LAR®

This is a Phase II, open-label multicentre, randomised study to assess the PK, PD, efficacy, and safety of two dosing regimens of CAM2029 in adult patients with acromegaly or a functional, well-differentiated NET, with carcinoid symptoms.

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Tumors; Acromegaly
• Intervention / Treatment: Drug: octreotide FluidCrystal® injection depot

Detailed Description

This is a Phase II, open-label multicentre, randomised study to assess the PK, PD, efficacy, and safety of two dosing regimens of CAM2029 in adult patients with acromegaly or a functional, well-differentiated NET, with carcinoid symptoms, treated for at least 2 months with Sandostatin LAR at doses of 10 mg, 20 mg, or 30 mg before the start of the Sandostatin LAR Last Dose Assessment Phase (Day -28).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bron, France
    • Hospices Civils de Lyon
  • Rouen cedex, France
    • CHU Rouen, Hôpital Charles Nicolle
• Germany
  • Bad Berka, Germany
    • Abteilung: Klinische Studien
  • Berlin, Germany
    • Charite Campus Virchow Klinikum
  • Essen, Germany
    • Universitatsklinikum Essen
• Italy
  • Genova, Italy
    • RCCS Azienda Ospedaliera Universitaria San Martino IST
  • Milano, Italy
    • Fondazione IRCCS Ca' Granda
  • Napoli, Italy
    • Università degli Studi di Napoli Federico II
  • Rozzano, Italy
    • Istituto Clinico Humanitas
• Sweden
  • Uppsala, Sweden
    • Akademiska Sjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Acromegaly:

• Male or female patients ≥18 years of age
• Acromegaly currently treated with Sandostatin LAR

NET:

• Male or female patients ≥18 years of age
• Functional, well-differentiated (Grade 1 or Grade 2) NET with symptoms of carcinoid syndrome (number of bowel movements and/or flushing)
• Currently treated with Sandostatin LAR for symptom control

Exclusion Criteria:

Acromegaly:

• Inadequate bone marrow function
• Abnormal coagulation or chronic treatment with warfarin or coumarin derivates
• Impaired liver, cardiac and/or renal function
• Known gallbladder, bile duct disease or pancreatitis
• Diabetes with poorly controlled blood glucose levels despite adequate therapy
• Hypothyroidisms not adequately treated

NET:

• Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, pancreatic islet cell carcinoma, insulinoma, glucagonoma, gastrinoma, goblet cell carcinoid, typical and atypical lung carcinoids, large cell neuroendocrine carcinoma and small cell carcinoma
• Carcinoid syndrome refractory to treatment with conventional doses of somatostatin analogues (SSAs)
• Inadequate bone marrow function
• Abnormal coagulation or chronic treatment with warfarin or coumarin derivates
• Impaired liver, cardiac and/or renal function
• Known gallbladder, bile duct disease or pancreatitis
• Short-bowel syndrome
• Diabetics with poorly controlled blood glucose levels despite adequate therapy
• Hypothyroidism, not adequately treated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAM2029 10 mg (NET); CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks	Drug: octreotide FluidCrystal® injection depot; Other Names: CAM2029
Experimental: CAM2029 20 mg (NET); CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly	Drug: octreotide FluidCrystal® injection depot; Other Names: CAM2029
Experimental: CAM2029 10 mg (Acromegaly); CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks	Drug: octreotide FluidCrystal® injection depot; Other Names: CAM2029
Experimental: CAM2029 20 mg (Acromegaly); CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly	Drug: octreotide FluidCrystal® injection depot; Other Names: CAM2029

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC	Pharmacokinetics (PK) of octreotide after injection of Sandostatin Long-acting Release (LAR) was determined for the dosing period Day -28 to Day 0; AUC0-28d (day*ng/mL). AUC0-28d: AUC from 0 to 28 days over the final dosing interval (day*ng/mL) for Sandostatin LAR.	Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC.	Pharmacokinetics (PK) of octreotide after administrations of CAM2029 was determined for the dosing period Day 0 to Day 84 ; AUC0-28d (day*ng/mL). AUC0-28d: AUC from 0 to 28 days over the dosing intervals (day*ng/mL) for CAM2029 20 mg q4w and CAM2029 10 mg q2w (to estimate AUC0-28d for those patients receiving CAM2029 10 mg q2w, AUC0-14d was multiplied by a factor of 2 as an estimate of the AUC0-28d) dosing intervals	(Day 0) to Day 84 (PK analysis:CAM2029 sampling time points: CAM2029 10mg q2w; 0, 2hours, 24hours, 48hours, 7days and 14days CAM2029 20mg q4w; 0, 2hours, 24hours, 48hours, 7days, 21days and 28days)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Ctrough	Pharmacokinetics (PK) of octreotide after injection of Sandostatin Long-acting Release (LAR) was determined for the dosing period Day -28 to Day 0; Ctrough (ng/mL). Ctrough; Concentration levels assessed prior to next injection for the final (Sandostatin LAR) dosing interval (ng/mL).	Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax	Pharmacokinetics (PK) of octreotide after injection of Sandostatin Long-acting Release (LAR) was determined for the dosing period Day -28 to Day 0; Cmax (ng/mL). Cmax (ng/mL): Maximum observed plasma concentration over the final (Sandostatin LAR) dosing interval (ng/mL)	Pre-dose; study Day -28- to Day 0 (PK analysis:Sandostatin (LAR®) sampling time points: 0, 1hour, 24hours, 7days, 14days, 21days and 28days)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Ctrough	Pharmacokinetics (PK) of octreotide after administrations of CAM2029 was determined for the dosing period Day 0 to Day 84; Ctrough (ng/mL). Ctrough; Concentration levels assessed prior to next injection for CAM2029 20 mg q4w and CAM2029 10 mg q2w dosing intervals (ng/mL)	(Day 0) to Day 84 (PK analysis:CAM2029 sampling time points: CAM2029 10mg q2w; 0, 2hours, 24hours, 48hours, 7days and 14days CAM2029 20mg q4w; 0, 2hours, 24hours, 48hours, 7days, 21days and 28days)
Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax.	Pharmacokinetics (PK) of octreotide after administrations of CAM2029 was determined for the dosing period Day 0 to Day 84 ; Cmax (ng/mL). Cmax (ng/mL): Maximum observed plasma concentration over CAM2029 20 mg q4w and CAM2029 10 mg q2w dosing intervals (ng/mL)	(Day 0) to Day 84 (PK analysis:CAM2029 sampling time points: CAM2029 10mg q2w; 0, 2hours, 24hours, 48hours, 7days and 14days CAM2029 20mg q4w; 0, 2hours, 24hours, 48hours, 7days, 21days and 28days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events and Serious Adverse Events	Safety (number of adverse events and serious adverse events) after repeated doses of CAM2029 (assessment period from Day 0 to Day 84) and single dose Sandostatin LAR (assessment period Day -28 to Day 0)	Day -28 to Day 84
CAM2029 Effect on Insulin-like Growth Factor (IGF-1) (Acromegaly)	Data is presented as number of patients; Within the reference limits (see below); Above ULN (Upper Limits of Normal) In the Acromegaly group both males and females were included the age was between 42-70 years. The IGF normal range for the different genders and age are presented below. REFERENCE VALUES Males (NMOL/L) 8.34-27.44 (41-45 years) 7.7-26.36 (46-50 years) 7.3-26.34 (51-55 years) 6.64-25.44 (56-60 years) 6.17-25.02 (61-65 years) 5.96-25.48 (66-70 years) Females (NMOL/L) 8.06-26.89 (41-45 years) 7.39-25.44 (46-50 years) 6.92-24.98 (51-55 years) 5.92-22.7 (56-60 years) 5.42-21.96 (61-65 years) 5.07-21.97 (66-70 years)	Day 84
CAM2029 Effect on Growth Hormone (GH) (Acromegaly)	GH (growth hormone) levels measured on Day 84 in patients with acromegaly	Day 84

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess the Symptoms of Carcinoid Syndrome (Number of Bowel Movements and Flushing) and the Use of Rescue Medication Versus Baseline (by Using Patient Diaries) (NET)	Number of bowel movements and flushing during period 0 and 1, data is presented as patients experience symptoms Bowel movement without flushing Bowel movement and flushing No Bowel movement or Flushing	Baseline (Day 0), Day 84

Collaborators and Investigators

• Sponsor: Camurus AB
• Collaborators: Novartis
• Investigators: Principal Investigator: Marianne Pavel, Professor, Charité Campus Virchow Klinikum, Berlin, Germany

Publications and helpful links

General Publications

• Pavel M, Borson-Chazot F, Cailleux A, Horsch D, Lahner H, Pivonello R, Tauchmanova L, Darstein C, Olsson H, Tiberg F, Ferone D. Octreotide SC depot in patients with acromegaly and functioning neuroendocrine tumors: a phase 2, multicenter study. Cancer Chemother Pharmacol. 2019 Feb;83(2):375-385. doi: 10.1007/s00280-018-3734-1. Epub 2018 Dec 8.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: November 17, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): December 15, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: acromegaly; octreotide; Sandostatin LAR; neuroendocrine tumour (NET); carcinoid syndrome
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Endocrine System Diseases; Musculoskeletal Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly; Neuroendocrine Tumors; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: HS-12-455

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share IPD