Pasireotide in Combination With RAD001 in Patients With Advanced Neuroendocrine Tumors

NCT00804336 | Completed Phase 1 DMC

• 1 other identifier: 08-087
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to determine the safety of the combination of SOM230 and RAD001, as well as determine the highest dose of this combination that can be given to people safely. SOM230 is an investigational drug that is similar to Sandostatin LAR. Sandostatin is an approved drug for the use of treating symptoms of neuroendocrine tumors. SOM230 has shown to be effective in patients who have become resistant to Sandostatin and may also stop cancer cells from growing. RAD001 is an investigational drug that also may stop cancer cells from growing.

Conditions

Neuroendocrine Tumor; Carcinoid Tumor; Pancreatic Neuroendocrine Tumor

Keywords

pasireotide; SOM230; RAD001

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose for pasireotide (SOM230) in combination with RAD001 in this patient population.

  2 years

• To determine the dose-limiting toxicities of the combination in this patient population.

  2 years

Secondary Outcomes (5)

• To determine the pharmacokinetics of combined treatment

  2 years

• To make a preliminary assessment of the anti-tumor activity of the combination in this patient population

  2 years

• To determine the objective response rate

  3 years

• To determine the duration of response

  3 years

• To determine the progression free survival and overall survival of patients receiving this combination.

  5 years

Study Arms (1)

Pasireotide and RAD001

EXPERIMENTAL

RAD001 was administered orally as a once-daily dose. Pasireotide s.c. was self-administered s.c. twice daily for 4 weeks. If pasireotide s.c. was tolerated, patients received pasireotide LAR i.m. at the corresponding dose level. Pasireotide s.c. was continued for an additional 2 weeks after administration of pasireotide LAR until anticipated steady-state levels of pasireotide LAR were achieved. Pasireotide LAR was administered every 28 days. Cycles for everolimus and pasireotide LAR were repeated every 28 days.

Drug: SOM230; Drug: RAD001

Interventions

SOM230 DRUG

Given subcutaneously twice a day for four weeks then given intramuscularly once every four weeks thereafter

Also known as: pasireotide

Pasireotide and RAD001

RAD001 DRUG

Given orally once a day

Pasireotide and RAD001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Locally unresectable or metastatic neuroendocrine tumor. Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid, and small cell carcinoma are not eligible.
• years of age or older
• Minimum of four weeks since any major surgery, completion of radiation, of completion of all prior systemic anticancer therapy.
• ECOG Performance Status 0,1, or 2.
• Life expectancy 12 weeks or more.
• Adequate bone marrow, liver and renal function as outlined in the protocol
• Negative serum pregnancy test for women of childbearing potential.
• Fasting serum cholesterol less than or equal to 300mg/dL or less than or equal to 7.75mml/L AND fasting triglycerides of less than or equal to 2.5 x ULN.

You may not qualify if:

• Chronic treatment with systemic steroids or another immunosuppressive agent.
• Immunization with attenuated live vaccines during study or within 1 week of study entry.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• Prior or concurrent malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
• Uncontrolled diabetes mellitus or a fasting plasma glucose of \> 1.5 ULN.
• Symptomatic cholelithiasis
• Congestive heart failure, unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment.
• Presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result.
• Any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as: severely impaired lung function; active or uncontrolled infection/disorders; nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by treatment with the study therapy; impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001; history of alcohol or drug abuse in the 6 month period prior to receiving treatment.
• Known hypersensitivity to RAD001 or other rapamycins or its excipients.
• Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR or s.c. formulations.
• History of non-compliance to medical regimens.
• Patients taking medication known to inhibit, induce, or be a substrate to isoenzyme CYP3A.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• Novartis: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Related Publications (1)

• Chan JA, Ryan DP, Zhu AX, Abrams TA, Wolpin BM, Malinowski P, Regan EM, Fuchs CS, Kulke MH. Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors. Endocr Relat Cancer. 2012 Sep 14;19(5):615-23. doi: 10.1530/ERC-11-0382. Print 2012 Oct.

  PMID: 22736724 RESULT

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoid Tumor; Adenoma, Islet Cell

Interventions

pasireotide; Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Adenoma; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jennifer Ang Chan, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 5, 2008
• First Posted: December 8, 2008
• Study Start: October 1, 2008
• Primary Completion: September 1, 2014
• Study Completion: April 1, 2015
• Last Updated: October 19, 2016

Record last verified: 2016-10

Locations

US (3)