Neoplasms

All Conditions

Rare Diseases

Carcinoma

Neuroendocrine Tumors

Carcinoma, Neuroendocrine

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Axitinib

Octreotide

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Hormonal

Axitinib 5 mg BID + Sandostatin LAR 30mg/28 days

Placebo BID + Sandostatin LAR 30mg/28 days

Orally, 5mg, twice daily, until progression or until unacceptable toxicity, with or without food intake.

Intramuscular, 30mg, single injection every 28 days, until disease progression or unacceptable toxicity

Sandostatin LAR

orally, twice daily, until disease progression or unacceptable toxicity, with or without food intake.

Placebo

Rocio Garcia Carbonero, MD

Assess whether therapy with axitinib, a potent angiogenic inhibitor of the tyrosine kinase receptors of VEGF bioavailable by oral administration, is capable of improving PFS in patients with advanced G1-G2 NETs of nonpancreatic origin with progressive disease documented in the 12 months prior to entering the study.

Phase II/III, prospective, multicenter, randomized (1:1), double-blind study to evaluate the efficacy and tolerability of axitinib in patients diagnosed with advanced G1-G2 neuroendocrine tumors (WHO 2010) of nonpancreatic origin that have presented documented disease progression in the 12 months prior to entering the study. In the first part of the study (Phase II), 105 patients were enrolled. The second part of the study is the expansion to Phase III, which is expected to include 148 additional patients. Patients will be randomized to receive Sandostatin LAR with axitinib or Sandostatin LAR with placebo until disease progression or unacceptable toxicity occurs. Randomization will be stratified by the time from diagnosis to enrollment in the study (more vs less than or equal to 12 months), the origin of the primary tumor (gastrointestinal tract vs non-gastrointestinal tract \[lung or other sites\]) and ki-67 (\< 5% vs \> 5%).

Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas

A Phase II/III Randomized Double-blind Study of Sandostatin LAR in Combination With Axitinib Versus Sandostatin LAR With Placebo in Patients With Advanced G1-G2 Neuroendocrine Tumours (WHO 2010) of Non-pancreatic Origin

calculated from the date of random assignment until the date of first progressive disease or tumor-related death

Measured according to RECIST 1.1 criteria; Sum of longest diameter of target lesions measured in mm

measured in SUV (standardized uptake value)

measurable in mL/ 24h and ng/ml respectively, through blood and urine test

All adverse events and serious adverse events will be monitored with regular monitoring of hematology and blood chemistry parameters and regular physical examinations. Adverse events will be evaluated continuously throughout the study. Safety and tolerability will be assessed according to the National Institute of Health/National Cancer Institute (NIH/NCI) Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)

The following parameters will be measured: circulating tumor cells, circulating endothelial cells, hypertension (mmHg), and other serum or tumoral biomarkers of angiogenesis).

Peripheral blood samples (9ml) will be obtained before treatment, after 1 month since the start of treatment and after disease progression and or the end of study visit. The blood samples will be processed for mRNA extraction. Hypoxia dependant genes and marker genes which transcription depends on the activation of VEGF, will be analyzed using qPCR. The dynamic profile of those genes will then be analyzed in relation to the response to axitinib, evaluating their predictive value of response.

Paraffin-embedded tumor tissue will also be collected from all patients to investigate the prognostic value and predictive potential of the different intracellular pathways related to VEGFR, PDGFR and other signaling pathways.

Pfizer

Grupo Espanol de Tumores Neuroendocrinos

Musculoskeletal Diseases

Nervous System Diseases

Gland and Hormone Related Diseases

Acromegaly

Bone Diseases

Bone Diseases, Endocrine

Pituitary Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Gastro-enteropancreatic Neuroendocrine Tumor

Lanreotide

Participants will receive Sandostatin Long-acting repeatable (LAR) or Somatuline Autogel (ATG) (or equivalent formulations of octreotide/lanreotide) in Run-in Period and further will receive Debio 4126 in this group.

Participants will receive Sandostatin LAR or Somatuline ATG (or equivalent formulations of octreotide/lanreotide) in Run-in Period and further will receive Debio 4126 in this group.

Debio 4126

Sandostatin LAR will be administered as IM injection as pre-study treatment dose prior to Debio 4126 administration

Somatulin ATG will be administered as deep subcutaneous (SC) injection as pre-study treatment dose prior to Debio 4126 administration

Somatuline ATG

This is an open-label, single treatment arm, multicenter study to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of Debio 4126 in the treatment of participants with Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine tumors (GEP-NETs).

A Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Debio 4126 in Participants With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

A Phase 1b Study in Patients With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) to Characterize the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Debio 4126, a 12-week Prolonged-release Octreotide Formulation

The PK of Debio 4126 will be evaluated in plasma.

Pain VAS scale score will be assessed on 4-point rating scale, where 0=absent and 3=severe.

The blood samples will be collected to assess changes in the levels of IGF-1 (in µg/L) and GH (in µg/L).

Debiopharm International SA

Digestive System Diseases

Carcinoid Tumor

Carcinoma, Islet Cell

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Pancreatic Cancer

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Immunosuppressive Agents

Immunologic Factors

RAD001 at 5 or 10 milligrams orally once a day plus Octreotide Depot 30 milligrams intramuscularly once every 28 days.

Starting dose of 5 or 10 mg by mouth daily.

RAD001

30 mg injection into the muscle of either buttock once every 28 (±7) days.

Octreotide Depot

James Yao, M.D.

Objectives:

Primary endpoint:

-Assess the clinical activity of RAD 001 plus depot octreotide as defined by progression free survival (PFS) duration defined by RECIST criteria in treated and untreated patients with metastatic, unresectable low grade neuroendocrine carcinoma.

Secondary endpoints:

* Assess the progression free survival duration of patients with metastatic, unresectable low grade neuroendocrine carcinoma treated with RAD 001 plus depot octreotide.
* Assess the safety of RAD 001 plus depot octreotide in patients with metastatic, unresectable low grade neuroendocrine carcinoma.
* To determine the expression/phosphorylation status of the components of the mTOR signaling pathway in the primary tumors, in order to determine whether these markers can be used as predictors of sensitivity to the combination of RAD001 and octreotide.
* To determine the effect of the combination of RAD001 and octreotide on the expression and phosphorylation of mTOR's targets in the accessible tumor tissue, in order to identify potential pharmacodynamics markers of response to this drug combination.
* To observe the effects of treatment with RAD001 on plasma angiogenic biomarkers.

RAD001 is a new drug that is designed to block a protein that is important in the growth of cancer cells. Octreotide Depot is FDA approved for the treatment of carcinoid syndrome and hormonal symptoms from certain islet cell carcinomas. Octreotide Depot may also help to block certain proteins that are important in tumor growth.

Before you can start treatment on the study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your heart rate, temperature, breathing rate, blood pressure, height, and weight will be measured. You will be asked about your ability to perform every day activities. Blood (about 2 teaspoons) will be collected for routine tests. You will have an electrocardiogram (ECG - a test that measures the electrical activity of the heart) and scans (either Computed Tomography/CT or Magnetic Resonance Imaging/MRI) to evaluate the cancer. Women who are able to have children must have a negative blood pregnancy test.

If the screening evaluations show you are eligible to take part in the study, you may begin treatment. You will take RAD001 by mouth once a day, every day while on study. You should take it in a fasting state or after no more than a light, fat-free meal. You should take RAD001 about the same time each day. Octreotide Depot will be given as an injection into the muscle of either buttock once every 4 weeks while on study. This will be done at M. D. Anderson. Four weeks (28 days) is called one course of treatment.

Clinic visits will occur every 2 weeks during the first 4 weeks and every 4 weeks from then on. At each clinic visit, you will be asked questions about your medical history and about any medications you are currently taking or have taken in the past. You will have a complete physical exam and your heart rate, temperature, breathing rate, blood pressure, height, and weight will be measured. You will be asked about your ability to perform every day activities. Blood samples (about 1 teaspoons) for routine tests will be collected every 2 weeks for the first 8 weeks. After that, blood samples (about 2 teaspoons) will be collected every 4 weeks. CT or MRI scan(s) will be performed every 12 weeks.

If a sample of your tumor tissue that was removed previously is available, it will be analyzed for expression of proteins that may effect tumor growth. However, if a sample is not available, you will not be asked to undergo a biopsy to collect this tissue. This sample may analyzed at any time during the study.

If you experience severe side effects, treatment may be delayed, stopped, or you may receive smaller doses of RAD001 and/or Octreotide Depot. You may continue to receive up to at least 12 courses of study treatment unless the disease gets worse, you decide not to take part any longer, or your doctor decides it is in your best interest to stop treatment. It may be possible to continue treatment beyond 12 courses if you are benefitting from this treatment.

When you stop study treatment, you will be asked to have some tests and evaluations done. About 4 teaspoons of blood will be taken for routine lab tests, You will also have a physical exam and CT scan or MRI scan will be done to check the size and location of your disease.

This is an investigational study. RAD001 is investigational and is not commercially available. The drug combination in this study is also investigational. RAD001 is manufactured by Novartis Pharmaceuticals Corporation. About 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

RAD001 Plus Octreotide Depot in Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma

Phase II Study of RAD001 Plus Octreotide Depot in Patients With Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma (Carcinoid, Islet Cell)

PFS is measured from date of trial entry until documented progression of disease or death from any cause. PFS is measured by computed tomography (CT) scans or magnetic resonance imaging (MRI) performed at baseline and after every three cycles.

Novartis Pharmaceuticals

M.D. Anderson Cancer Center

RAD001 at 5 or 10 milligrams orally once a day plus Octreotide Depot 30 milligrams intramuscularly once every 28 days

RAD001 Plus Octreotide Depot

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

James Yao, M.D./Associate Professor

Progression Free Survival (PFS)

Overall Study

Symptoms and General Pathology

Substance Related Disorders

Syndrome

Malignant Carcinoid Syndrome

Serotonin Syndrome

Carcinoid Syndrome

CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks

CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly

octreotide FluidCrystal® injection depot

Marianne Pavel, Professor

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.

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).

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®

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

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.

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

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).

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)

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)

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)

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)

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)

GH (growth hormone) levels measured on Day 84 in patients with acromegaly

Novartis

Camurus AB

CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks

octreotide FluidCrystal® injection depot Day 0-84

CAM2029 10 mg q2w (Acromegaly)

CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly

octreotide FluidCrystal® injection depot Day 0-84

CAM2029 20 mg q4w (Acormegaly)

CAM2029 10 mg q2w (NET)

CAM2029 20 mg q4w (NET)

Sandostatin LAR Day-28 to day 0 All acromegaly patients, all treatment groups

Sandostatin LAR (Acromegaly)

Sandostatin LAR Day -28 to day 0 All NET patients, all treatment groups

Sandostatin LAR (NET)

CAM2029 (octreotide FluidCrystal® injection depot) 10 mg, subcutaneous injection every two weeks

octreotide FluidCrystal® injection depot

CAM2029 (octreotide FluidCrystal® injection depot) 20 mg, subcutaneous injection once monthly

octreotide FluidCrystal® injection depot

CAM2029 20 mg q4w (Acromegaly)

Total

Age, Categorical

Italy

France

Germany

Clinical Trial Manager

Study injection (period 0) pre-CAM2029 treatment (day -28 to D0) of their ongoing maintenance therapy with Sandostatin LAR

Sandostatin LAR 10 mg (Acromegaly)

Sandostatin LAR 30mg (Acromegaly)

Sandostatin LAR 20 mg (NET)

Sandostatin LAR 30 mg (NET)

Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC

AUC0-28d (day*ng/mL) Day 0

AUC0-28d (day*ng/mL) Day 56

Pharmacokinetic population, two patients excluded from the CAM2029 20mg Acromegaly due to incorrect dose.

Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) AUC.

Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Ctrough

Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax

Ctrough (ng/mL) Day 0

Ctrough (ng(mL) Day 56

Cmax (ng/mL) Day 0

Cmax (ng/mL) Day 56

Pharmacokinetic (PK) Profile of Octreotide After Each Injection of CAM2029 as Compared With Baseline PK for Sandostatin® Long-acting Release (LAR®) Cmax.

Period day -28 to day 0 All acromegaly patients and all treatment groups

Period day-28 to 0 All NET patient and all treatment groups

Sandostain LAR (NET)

Safety population (n=12). Patients treated with Sandostatin LAR Day -28 to 0 and CAM2029 (Day 0 to Day 84)

Number of Adverse Events and Serious Adverse Events

Within Normal Limits

Above ULN

Pharmacokinetic population (5 acromegaly subjects total)

CAM2029 Effect on Insulin-like Growth Factor (IGF-1) (Acromegaly)

GH level < 2.5 μg/L

GH level >2.5 μg/L

Pharmacokinetic population (5 acromegaly patients)

CAM2029 Effect on Growth Hormone (GH) (Acromegaly)

Bowel movements without flushing

Bowel movements with flushing

No Bowel movement or Flushing

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)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas	NCT01744249	Neuroendocrine ... Advanced Cancer	Axitinib Sandostatin LAR Placebo	18 Years -	Grupo Espanol de Tumores Neuroendocrinos
Sandostatin LAR and Axitinib vs Pbo in Pnts With Advanced Well-differentiated Non-pancreatic Neuroendocrine Carcinomas	NCT01744249	Neuroendocrine ... Advanced Cancer	Axitinib Sandostatin LAR Placebo	18 Years -	Grupo Espanol de Tumores Neuroendocrinos
A Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Debio 4126 in Participants With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)	NCT05364944	Acromegaly GEP-NET	Debio 4126 Sandostatin LAR Somatuline ATG	18 Years -	Debiopharm International SA
RAD001 Plus Octreotide Depot in Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma	NCT00113360	Neuroendocrine ... Islet Cell Carc...	RAD001 Octreotide Depo...	18 Years -	M.D. Anderson Cancer Center
A Study to Assess the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Debio 4126 in Participants With Acromegaly or Functioning Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)	NCT05364944	Acromegaly GEP-NET	Debio 4126 Sandostatin LAR Somatuline ATG	18 Years -	Debiopharm International SA
Phase II Study of Subcutaneous Inj. Depot of Octreotide in Patients With Acromegaly and Neuroendocrine Tumours (NETs)	NCT02299089	Acromegaly Neuroendocrine ...	octreotide Flui...	18 Years -	Camurus AB
Phase II Study of Subcutaneous Inj. Depot of Octreotide in Patients With Acromegaly and Neuroendocrine Tumours (NETs)	NCT02299089	Acromegaly Neuroendocrine ...	octreotide Flui...	18 Years -	Camurus AB

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