RAD001 in Previously Treated Patients With Metastatic Pancreatic Cancer

Phase II Study of RAD001 in Previously Treated Patients With Metastatic Pancreatic Cancer

The purpose of this research study is to investigate if RAD001 is an effective treatment for pancreatic cancer that has spread and not responded to treatment. Experiments have shown that RAD001 can prevent cells from multiplying. RAD002 has also been tested in laboratory experiments imitating cancer conditions and the results have been promising.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: RAD001

Detailed Description

• Participants taking part in this research study will be given a study medication-dosing calendar for each treatment cycle. Each cycle lasts four weeks during which you will be taking the study drug, RAD001, orally every day.
• Participants will come into the clinic every other week during the time of enrollment. At each clinic visit blood work will be taken to monitor the participants health and a physical exam will be performed. CT scans will be repeated every 2 months to assess the tumor.
• Participants will remain on the study as long as they continue to benefit from the study medication.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center

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:

• Pathologic confirmation of pancreatic adenocarcinoma
• 18 years of age or older
• At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Treated with gemcitabine-based chemotherapy with documented tumor progression on gemcitabine or intolerance to gemcitabine.
• Prior treatment with no more than 1 prior chemotherapy regimen for metastatic disease.
• Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anti-cancer therapy.
• ECOG performance status 0-1.
• Life expectancy of greater than 12 weeks.
• Adequate bone marrow and liver function.
• Must be able to swallow tablets.

Exclusion Criteria:

• Prior treatment with an investigational drug within the preceding 4 weeks.
• Prior treatment with an inhibitor of mTOR
• Chronic treatment with systemic steroids or another immunosuppressive agent
• More than one prior chemotherapy treatment for metastatic disease
• Uncontrolled brain or leptomeningeal metastases, including patient who continue to require glucocorticoids for brain or leptomeningeal metastases.
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Patients with chronic renal insufficiency
• Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study.
• Known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that my significantly alter the absorption of RAD001.
• Active, bleeding diathesis or an oral vitamin K antagonist medication
• Women who are pregnant or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAD001; RAD001 was administered continuously at a dose of 10 mg daily by mouth until disease progression, unacceptable toxicity, or withdrawal of consent. Four weeks of study drug was considered to be one cycle of treatment.	Drug: RAD001; Taken orally daily for as long as the participant continues to receive a benefit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess Progression-free Survival of RAD001 at Two Months in Patients With Metastatic Pancreatic Cancer Whose Disease Has Progressed on Gemcitabine Chemotherapy.	The Outcome Measure is reporting the number of participants experiencing Progression-free Survival at 2 months after treatment. The study was designed with a primary end point of progression-free survival (PFS), defined as the time from study entry to documentation of progressive disease or death from any cause. On the basis of prior studies of second-line treatment in metastatic pancreatic cancer, we estimated that such treatment has been associated with a median PFS of 2 months. Our study design used a one-stage design with a target accrual of 35 eligible patients, with the assumption that an improvement in PFS at 2 months from 50% to 71% would warrant further study in this patient population.	two months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess the Safety of RAD001 in Patients With Metastatic Pancreatic Cancer	Patients were followed for the duration of their time on treatment and 30 days after their last dose of RAD001. The number of patients with treatment-related adverse events are reported.	Patients were followed for the duration of their time on treatment and 30 days after their last dose of RAD001.
to Assess Response Rate Associated With RAD001 in This Patient Population.	The secondary objectives of the study were to assess tumor response rate and overall survival. Patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST, for target lesions assessed by CT: Complete Response (CR) is Disappearance of all target lesions; Partial Response (PR) is >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) equals CR + PR.	2 years
to Assess Overall Survival Associated With RAD001 in This Patient Population.	Overall survival was defined as the time from study entry until death from any cause.	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Massachusetts General Hospital; Novartis; Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Charles Fuchs, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Wolpin BM, Hezel AF, Abrams T, Blaszkowsky LS, Meyerhardt JA, Chan JA, Enzinger PC, Allen B, Clark JW, Ryan DP, Fuchs CS. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol. 2009 Jan 10;27(2):193-8. doi: 10.1200/JCO.2008.18.9514. Epub 2008 Dec 1.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: December 6, 2006
• First Submitted That Met QC Criteria: December 6, 2006
• First Posted (Estimate): December 8, 2006

Study Record Updates

• Last Update Posted (Estimate): August 11, 2014
• Last Update Submitted That Met QC Criteria: July 23, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: metastatic pancreatic cancer; RAD001
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: 06-197