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RAD001 in Advanced Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RAD001

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer, RAD001

Eligibility Criteria

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

Inclusion Criteria:

Unresectable of metastatic HCC. Patients must have prior core biopsy to confirm the diagnosis of HCC and have archived tissues available for correlative studies
At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If it has had previous radiation to teh marker lesion(s), there must be evidence of progression since the radiation
0-2 prior systemic chemotherapy and biologic regimens for hepatocellular carcinoma
Patients with prior chemoembolization history can participate in the study if the chemoembolization was performed more than 4 weeks ago and patients must have measurable disease outside of prior chemoembolization field
18 years of age or older
Minimum of 4 weeks since any major surgery or completion of radiation
Minimum of 4 weeks since completion of all prior systemic anticancer therapy
ECOG performance status of 0-2
CLIP score of equal to or less then 3
Adequate bone marrow, liver and renal function as outlined in the protocol

Exclusion Criteria:

Prior treatment with any investigational drug within the preceding 4 weeks
Chronic treatment with systemic steroids or another immunosuppressive agent
Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
Patients with any severe and/or uncontrolled medical conditions or other condition that could affect participation in the study
Known history of HIV seropositivity
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
Active, bleeding diathesis
Women who are pregnant or breast feeding
Patients who have received prior treatment with an mTor inhibitor
Patients with known hypersensitivity to RAD001 or other rapamycins or its excipients
History of non-compliance to medical regimens
Patients with a positive dipstick for urine protein (reading of 2+ or greater) will then undergo a 24-hour urine collection for protein. If patients have a 2g or greater of protein/24hr, they will be excluded from the study.

Sites / Locations

Massachusetts General Hospital
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001

Arm Description

Patients will receive RAD001 10 mg/day orally (6 weeks/cycle). Patients will be continued on treatment until disease progression, limiting toxicity, patient withdrawal of consent, or death.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).

Progression-free Survival Rate at 24 Weeks

Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions" This information will be collected during two years of patient participation.

Secondary Outcome Measures

Number of Patients With Adverse Events Who Were Treated With RAD001 for Advanced HCC

Everolimus given at 10 mg/day as a single agent was well tolerated in patients with advanced HCC.

Overall Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Time to Progression

3.9 months with a CI of 21-

Overall Survival

The median overall survival was 8.4 months (95% CI, 3.9-21.1 months). Only 2 ((8 %) patients were progression-free at 24 weeks. The study did not proceed to the second stage of the phase 2 portion of the study.

Full Information

NCT ID

NCT00516165

First Posted

August 13, 2007

Last Updated

December 14, 2016

Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Novartis

1. Study Identification

Unique Protocol Identification Number

NCT00516165

Brief Title

RAD001 in Advanced Hepatocellular Carcinoma

Official Title

A Phase I/II Study of RAD001 in Advanced Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Novartis

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Laboratory studies have shown that RAD001 can prevent cells from multiplying. Consequently, the study drug is being tested in medical conditions in which excessive cell multiplication (as in cancer) needs to be stopped. The main purpose of this research study is to find the highest dose of RAD001 that can be given safely (without causing severe side effects) and to learn the effects (good or bad) RAD001 has on participants with liver cancer.

Detailed Description

Participants will be given a supply of the study drug RAD001 to be taken at home. They will be asked to take the study drug every morning on an empty stomach and will be given a study drug diary to record the time/date each time they take RAD001. Each 6 week period of time is called a cycle of study treatment. We are looking for the highest dose of RAD001 that can be given safely. Therefore not every participant will receive the same dose of RAD001. Participants will come to the clinic every other week. At each of these visits, a physical examination and blood tests will be performed. A CT and MRI will be repeated every 6 weeks during the first 3 cycles of treatment then every 12 weeks thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

liver cancer, RAD001

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RAD001

Arm Type

Experimental

Arm Description

Patients will receive RAD001 10 mg/day orally (6 weeks/cycle). Patients will be continued on treatment until disease progression, limiting toxicity, patient withdrawal of consent, or death.

Intervention Type

Drug

Intervention Name(s)

RAD001

Other Intervention Name(s)

Everolimus

Intervention Description

Oral pills taken daily in a 42-day cycle (6 weeks). Cycles will be repeated every 42 days

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).

Time Frame

2 years

Title

Progression-free Survival Rate at 24 Weeks

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Number of Patients With Adverse Events Who Were Treated With RAD001 for Advanced HCC

Description

Everolimus given at 10 mg/day as a single agent was well tolerated in patients with advanced HCC.

Time Frame

2 years

Title

Overall Response Rate

Description

Time Frame

2 years

Title

Time to Progression

Description

3.9 months with a CI of 21-

Time Frame

2 years

Title

Overall Survival

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Unresectable of metastatic HCC. Patients must have prior core biopsy to confirm the diagnosis of HCC and have archived tissues available for correlative studies At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If it has had previous radiation to teh marker lesion(s), there must be evidence of progression since the radiation 0-2 prior systemic chemotherapy and biologic regimens for hepatocellular carcinoma Patients with prior chemoembolization history can participate in the study if the chemoembolization was performed more than 4 weeks ago and patients must have measurable disease outside of prior chemoembolization field 18 years of age or older Minimum of 4 weeks since any major surgery or completion of radiation Minimum of 4 weeks since completion of all prior systemic anticancer therapy ECOG performance status of 0-2 CLIP score of equal to or less then 3 Adequate bone marrow, liver and renal function as outlined in the protocol Exclusion Criteria: Prior treatment with any investigational drug within the preceding 4 weeks Chronic treatment with systemic steroids or another immunosuppressive agent Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Patients with any severe and/or uncontrolled medical conditions or other condition that could affect participation in the study Known history of HIV seropositivity Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 Active, bleeding diathesis Women who are pregnant or breast feeding Patients who have received prior treatment with an mTor inhibitor Patients with known hypersensitivity to RAD001 or other rapamycins or its excipients History of non-compliance to medical regimens Patients with a positive dipstick for urine protein (reading of 2+ or greater) will then undergo a 24-hour urine collection for protein. If patients have a 2g or greater of protein/24hr, they will be excluded from the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew X. Zhu, MD, PhD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

19192962

Citation

Treiber G. mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther. 2009 Feb;9(2):247-61. doi: 10.1586/14737140.9.2.247.

Results Reference

derived

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RAD001 in Advanced Hepatocellular Carcinoma

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