Antiproliferative Effect of Octreotide in Patients With Metastasized Neuroendocrine Tumors of the Midgut

• Sponsor: Carmen Schade-Brittinger (Other)
• Overall Status: Completed
• CT.gov ID: NCT00171873
• Collaborator: (none)
• Enrollment: 85
• Locations: 10
• Arms: 2
• Duration (Months): 147
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Placebo-controlled prospective randomized phase III study to investigate the antiproliferative effect of octreotide in patients with metastasized neuroendocrine tumors of the midgut

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumors	Drug: Octreotide LAR (Long-acting release); Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study to Investigate the Antiproliferative Effect of Octreotide in Patients With Metastasized Neuroendocrine Tumors of the Midgut
• Study Start Date: Sep 1, 2001
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Octreotide LAR (Long Acting Release) Octreotide LAR 30 mg intramuscularly every 28 days	Drug: Octreotide LAR (Long-acting release); 30 mg intramuscularly every 28 days; Other Names: SMS995
Placebo Comparator: Placebo Placebo - Sodium chloride intramuscularly every 28 days	Drug: Placebo; Sodium chloride intramuscularly every 28 days

Outcome Measures

Primary Outcome Measures

1. Time to Tumor Progression Documented by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) [Up to 7 years]

   Median time to tumor progression at the time of the planned interim analysis that includes all data observed until June 2008.

Secondary Outcome Measures

1. Objective Response Rates According to World Health Organization (WHO) Criteria at 3 Month Intervals [at 3 month intervals]

2. Biochemical Response at 3 Month Intervals [at 3 month intervals up to 18 moths]

3. Symptom Control at 3 Month Intervals [at 3 month intervals up to 18 moths]

4. Quality of Life (Standardized Questionnaire) at Three-month Intervals in Comparison With the Start of the Study [at three-month intervals]

5. Survival [at least on a monthly basis]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Therapy-naive patients with histologically confirmed diagnosis of a locally inoperable or metastasized well-differentiated neuroendocrine tumor of the midgut

• curative surgery impossible

• two-dimensional tumor formation assessable by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)

• Age ≥ 18

• Karnofsky-index > 60

• written informed consent

• proliferation index for Ki67

Exclusion Criteria:

• hypersensitivity to octreotide

• poorly differentiated or small cell neuroendocrine tumors

• primary tumor outside of the midgut

• prior treatment with somatostatin-analogue > 4 weeks

• prior treatment with alpha-interferon, chemotherapy, or chemoembolisation

• participation in any other clinical trial

• pregnancy or lactation

• no secondary malignancy in anamnesis; with the exception of patients without any manifestation of the secondary malignancy (without relapse) after curative therapy within the last five years

• severe decompensated organ malfunction (heart-, liver- insufficiency)

Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Bochum		Germany
2	Novartis Investigative Site	Dresden		Germany
3	Novartis Investigative Site	Halle		Germany
4	Novartis Investigative Site	Hamburg		Germany
5	Novartis Investigative Site	Kiel		Germany
6	Novartis Investigative Site	Leipzig		Germany
7	Novartis Investigative Site	Mainz		Germany
8	Novartis Investigative Site	Marburg		Germany	35033
9	Novartis Investigative Site	Marburg		Germany
10	Novartis Investigative Site	Munchen		Germany

Sponsors and Collaborators

• Carmen Schade-Brittinger

Investigators

• Principal Investigator: Rudolf Arnold, MD, Prof, Philipps University Marburg Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Carmen Schade-Brittinger, Sponsor-representative, Philipps University Marburg Medical Center
• ClinicalTrials.gov Identifier: NCT00171873
• Other Study ID Numbers: CSMS995ADE05; NCT00202085
• First Posted: Sep 15, 2005
• Last Update Posted: Mar 26, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Carmen Schade-Brittinger, Sponsor-representative, Philipps University Marburg Medical Center: Double blind; Phase III; Disease; Clinical trial; Octreotide; Neuroendocrine tumor; Cancer; Tumor; Midgut
• Additional relevant MeSH terms: Neuroendocrine Tumors; Neoplasm Metastasis; Octreotide

Study Results

Participant Flow

Arm/Group Title	Octreotide LAR (SMS995)	Placebo
Arm/Group Description	Octreotide LAR (Long-acting release) 30 mg intramuscularly every 28 days	Sodium chloride intramuscularly every 28 days
Period Title: Overall Study
STARTED	42	43
COMPLETED	33	40
NOT COMPLETED	9	3

Baseline Characteristics

Arm/Group Title	Octreotide LAR (SMS995)	Placebo	Total
Arm/Group Description	Octreotide LAR (Long-acting release) 30 mg intramuscularly every 28 days	Sodium chloride intramuscularly every 28 days	Total of all reporting groups
Overall Participants	42	43	85
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.5	61	62
Sex: Female, Male (Count of Participants)
Female	22 52.4%	20 46.5%	42 49.4%
Male	20 47.6%	23 53.5%	43 50.6%

Outcome Measures

1. Primary Outcome

Title	Time to Tumor Progression Documented by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
Description	Median time to tumor progression at the time of the planned interim analysis that includes all data observed until June 2008.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

Conservative Intent to Treat (ITT) population consisting of all participants who received study drug. 3 participants in the Octreotide group and 1 participant in the placebo group without liver involvement at the beginning of the study were excluded from this analysis.

Arm/Group Title	Octreotide LAR (SMS995)	Placebo
Arm/Group Description	Octreotide LAR (Long-acting release) 30 mg intramuscularly every 28 days	Sodium chloride intramuscularly every 28 days
Measure Participants	39	42
Median (95% Confidence Interval) [Months]	14.3	6.0

2. Secondary Outcome

Title	Objective Response Rates According to World Health Organization (WHO) Criteria at 3 Month Intervals
Time Frame	at 3 month intervals

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Biochemical Response at 3 Month Intervals
Time Frame	at 3 month intervals up to 18 moths

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Symptom Control at 3 Month Intervals
Time Frame	at 3 month intervals up to 18 moths

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Quality of Life (Standardized Questionnaire) at Three-month Intervals in Comparison With the Start of the Study
Time Frame	at three-month intervals

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Survival
Time Frame	at least on a monthly basis

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Octreotide LAR (SMS995)		Placebo
Arm/Group Description	Octreotide LAR (Long-acting release) 30 mg intramuscularly every 28 days		Sodium chloride intramuscularly every 28 days
All Cause Mortality
	Octreotide LAR (SMS995)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Octreotide LAR (SMS995)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/42 (26.2%)		10/43 (23.3%)
General disorders
General Disorder	11/42 (26.2%)		10/43 (23.3%)
Other (Not Including Serious) Adverse Events
	Octreotide LAR (SMS995)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/42 (45.2%)		11/43 (25.6%)
Blood and lymphatic system disorders
Hematopoietic system	5/42 (11.9%)		1/43 (2.3%)
Gastrointestinal disorders
Gastrointestinal disorders	6/42 (14.3%)		8/43 (18.6%)
General disorders
General Health	8/42 (19%)		2/43 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.