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

Primary Purpose

Neuroendocrine Carcinoma, Islet Cell Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RAD001
Octreotide Depot
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Carcinoma focused on measuring Neuroendocrine Carcinoma, Low Grade Neuroendocrine Carcinoma, Neuroendocrine Carcinoid, Islet Cell Carcinoma, RAD001, Everolimus, Octreotide Depot, Sandostatin LAR, Octreotide long-acting release (LAR), Octreotide LAR

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with histologic proof of low grade neuroendocrine carcinoma will be eligible. Both carcinoid (any site[atypical/intermediate grade carcinoid is allowed]) and islet cell (pancreatic endocrine tumor) will be eligible. Patients with neuroendocrine tumors associated with MEN1 syndrome will be eligible. Patients must have either metastatic or unresectable local-regional cancer. Patients must have measurable disease, as defined by RECIST (Response Evaluation Criteria In Solid Tumors). Prior and concurrent octreotide (Sandostatin and Sandostatin LAR) is allowed. Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment. Patients may have received 0, 1, or 2 prior cytotoxic chemotherapy. Chemotherapy used as a radiosensitizer will be considered one prior chemotherapy regimen. Patients may have received prior interferon (not counted toward prior cytotoxic chemotherapy). Patients may have received prior therapy targeting c-kit, abl, PDGFR (Platelet Derived Growth Factor Receptor), VEGF (Vascular endothelial growth factor), or EGFR [epidermal growth factor receptor] (not counted toward prior cytotoxic chemotherapy). Patients may have had prior hepatic artery embolization. There must be residual measurable disease. Chemoembolization will be considered as one prior chemotherapy regimen. Patients must have a performance status of 0, 1, or 2 (Zubrod scale). Patients must be >/= 18 years old (age limit due to lack of adequate safety data in younger patients). Patients must give written informed consent. Patients should have adequate organ function defined as follows: Absolute granulocytes > 1,500/mm3, hemoglobin > 8 g/dl, and platelets > 100,000/mm3. Serum bilirubin < 1.5 x Upper Limit of Normal (ULN), serum creatinine < 1.5 mg/dL, AST (SGOT) less/equal 2.5 x ULN, ALT (SGPT) less/equal 2.5 x ULN. Patients must have recovered from recent surgery. One week must have elapsed from the time of a minor surgery and 4 weeks from major surgery. Fertile patients, both male and female, must practice contraception during treatment. Exclusion Criteria: Patients may receive no other concurrent chemotherapy, immunotherapy, or radiotherapy. Patients with intolerance to octreotide. Patients who have received chemotherapy, immunotherapy, or investigational therapy in the 30 days prior to registration. Patients with uncontrolled diabetes mellitus as defined by fasting blood sugar > 1.5 x ULN. Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to entry into the study. All patients of child-bearing potential must be advised of the importance of avoiding pregnancy and using appropriate methods of contraception while participating in this investigational trial. Women who have had menses within the past 2 years, who have not had a tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential. Appropriate methods of contraception include hormonal or barrier method of birth control; abstinence. Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy. Psychiatric disorders rendering them incapable of complying with the requirements of the protocol. Osseous metastasis as only site of disease. Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix. Patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial.

Sites / Locations

  • UT MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001 plus Depot Octreotide

Arm Description

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

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
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.

Secondary Outcome Measures

Full Information

First Posted
June 7, 2005
Last Updated
October 11, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00113360
Brief Title
RAD001 Plus Octreotide Depot in Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma
Official Title
Phase II Study of RAD001 Plus Octreotide Depot in Patients With Metastatic or Unresectable Low Grade Neuroendocrine Carcinoma (Carcinoid, Islet Cell)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Carcinoma, Islet Cell Carcinoma
Keywords
Neuroendocrine Carcinoma, Low Grade Neuroendocrine Carcinoma, Neuroendocrine Carcinoid, Islet Cell Carcinoma, RAD001, Everolimus, Octreotide Depot, Sandostatin LAR, Octreotide long-acting release (LAR), Octreotide LAR

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001 plus Depot Octreotide
Arm Type
Experimental
Arm Description
RAD001 at 5 or 10 milligrams orally once a day plus Octreotide Depot 30 milligrams intramuscularly once every 28 days.
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
Everolimus
Intervention Description
Starting dose of 5 or 10 mg by mouth daily.
Intervention Type
Drug
Intervention Name(s)
Octreotide Depot
Other Intervention Name(s)
Sandostatin LAR, Octreotide long-acting release (LAR), Octreotide LAR
Intervention Description
30 mg injection into the muscle of either buttock once every 28 (±7) days.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
PFS assessed every 12 weeks (at the end of every 3 cycles) or more frequently if clinically indicated

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histologic proof of low grade neuroendocrine carcinoma will be eligible. Both carcinoid (any site[atypical/intermediate grade carcinoid is allowed]) and islet cell (pancreatic endocrine tumor) will be eligible. Patients with neuroendocrine tumors associated with MEN1 syndrome will be eligible. Patients must have either metastatic or unresectable local-regional cancer. Patients must have measurable disease, as defined by RECIST (Response Evaluation Criteria In Solid Tumors). Prior and concurrent octreotide (Sandostatin and Sandostatin LAR) is allowed. Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment. Patients may have received 0, 1, or 2 prior cytotoxic chemotherapy. Chemotherapy used as a radiosensitizer will be considered one prior chemotherapy regimen. Patients may have received prior interferon (not counted toward prior cytotoxic chemotherapy). Patients may have received prior therapy targeting c-kit, abl, PDGFR (Platelet Derived Growth Factor Receptor), VEGF (Vascular endothelial growth factor), or EGFR [epidermal growth factor receptor] (not counted toward prior cytotoxic chemotherapy). Patients may have had prior hepatic artery embolization. There must be residual measurable disease. Chemoembolization will be considered as one prior chemotherapy regimen. Patients must have a performance status of 0, 1, or 2 (Zubrod scale). Patients must be >/= 18 years old (age limit due to lack of adequate safety data in younger patients). Patients must give written informed consent. Patients should have adequate organ function defined as follows: Absolute granulocytes > 1,500/mm3, hemoglobin > 8 g/dl, and platelets > 100,000/mm3. Serum bilirubin < 1.5 x Upper Limit of Normal (ULN), serum creatinine < 1.5 mg/dL, AST (SGOT) less/equal 2.5 x ULN, ALT (SGPT) less/equal 2.5 x ULN. Patients must have recovered from recent surgery. One week must have elapsed from the time of a minor surgery and 4 weeks from major surgery. Fertile patients, both male and female, must practice contraception during treatment. Exclusion Criteria: Patients may receive no other concurrent chemotherapy, immunotherapy, or radiotherapy. Patients with intolerance to octreotide. Patients who have received chemotherapy, immunotherapy, or investigational therapy in the 30 days prior to registration. Patients with uncontrolled diabetes mellitus as defined by fasting blood sugar > 1.5 x ULN. Pregnant or lactating women. All women of child-bearing potential must have a negative pregnancy test prior to entry into the study. All patients of child-bearing potential must be advised of the importance of avoiding pregnancy and using appropriate methods of contraception while participating in this investigational trial. Women who have had menses within the past 2 years, who have not had a tubal ligation, or bilateral oophorectomy are considered to be of child-bearing potential. Appropriate methods of contraception include hormonal or barrier method of birth control; abstinence. Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy. Psychiatric disorders rendering them incapable of complying with the requirements of the protocol. Osseous metastasis as only site of disease. Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix. Patients with previous malignancies but without evidence of disease for > 5 years will be allowed to enter the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Yao, M.D.
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center website

Learn more about this trial

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

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