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Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors

Primary Purpose

Neoplasm Metastases

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RAD001 + AMG479
Sponsored by
Shadia Jalal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm Metastases

Eligibility Criteria

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

Inclusion Criteria:

  • Histological or cytological proof of metastatic solid tumor refractory to standard therapies, or for which no standard therapies are available.
  • Patients in the expansion cohort must have a measurable site of disease according to RECIST (v 1.0)
  • Laboratory values must be obtained within protocol limits and obtained within 14 days prior to registration
  • Patients must have disease which is not amenable to potentially curative surgical resection of metastatic disease (curative metastasectomy).
  • Must be willing to provide metastatic tissue biopsy samples (may be paraffin embedded) at baseline
  • Must be willing to undergo a metastatic tissue biopsy after 2 cycles of therapy to perform pharmacodynamic research biomarkers testing.
  • Subjects must be willing and able to abstain from using strong or moderate CYP3A4 inhibitors or inducers during the study period.

Exclusion Criteria:

  • No symptomatic brain metastasis
  • No prior treatment with an mTOR inhibitor or with an IGF-1R inhibitor
  • No known history of diabetes mellitus
  • No thrombosis or vascular ischemic events within the last twelve months
  • No chronic treatment with systemic steroids or another immunosuppressive agent
  • No active bleeding or a pathological condition that is associated with a high risk of bleeding
  • No known history of HIV seropositivity
  • No known history of Hepatitis B or Hepatitis C seropositivity
  • No known hypersensitivity to AMG 479, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus), or to its excipients
  • No planned immunization with attenuated live viruses during the study period

Sites / Locations

  • Indiana University Melvin and Bren Simon Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open Label

Arm Description

RAD001+ AMG479

Outcomes

Primary Outcome Measures

To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors
To evaluate the grade and severity of adverse events as a measure of safety and toxicity

Secondary Outcome Measures

To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors
response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS)

Full Information

First Posted
May 7, 2010
Last Updated
May 9, 2017
Sponsor
Shadia Jalal
Collaborators
Amgen, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT01122199
Brief Title
Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors
Official Title
Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
May 14, 2010 (Actual)
Primary Completion Date
January 19, 2015 (Actual)
Study Completion Date
January 19, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Shadia Jalal
Collaborators
Amgen, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to test the safety of the combination of two drugs called RAD001 and AMG479. This study will see what effects (good and bad) RAD001 and AMG479 have on cancer. This study will also find the highest doses of RAD001 and AMG479 that can be given without causing severe side effects.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 (ganitumab) and RAD001 (everolimus) in patients with refractory solid tumors. II. To determine the safety and toxicity of AMG479 and RAD001. SECONDARY OBJECTIVES: I. To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors: response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS). II. For all patients, to analyze tumor and blood samples for pharmacodynamic biomarkers related to IGF-1R and mTOR signaling: pAkt, pS6, p-4EBP1, PTEN, IGF-1, IGF-2, pIGF-1R and IGFBP3 and correlate with response and stable disease. III. For all patients, to analyze the pharmacokinetic profile (PK) for RAD001 and AMG479, and correlate with response/stable disease and pharmacodynamic markers. IV. To evaluate the effects of RAD001 on AMG 479 pharmacokinetics. OUTLINE: This is a dose-escalation study. Patients receive everolimus orally (PO) once daily (QD) on days 1-28 (days 1-7 and 16-28 of course 1 only) and ganitumab intravenously (IV) over 60 minutes on days 1 and 15 (day 15 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at day 30, every 3 months for 2 years from registration for study treatment, every 6 months for years 3-5, and then annually thereafter.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open Label
Arm Type
Experimental
Arm Description
RAD001+ AMG479
Intervention Type
Drug
Intervention Name(s)
RAD001 + AMG479
Other Intervention Name(s)
everolimus + ganitumab
Intervention Description
Escalating doses of RAD001 + AMG479. Starting cohort will be 5 mg RAD001 once daily, continuous + AMG479 12 mg/kg on Day 1 and 15 of each 28 day cycle.
Primary Outcome Measure Information:
Title
To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors
Time Frame
1 year
Title
To evaluate the grade and severity of adverse events as a measure of safety and toxicity
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors
Description
response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS)
Time Frame
5-10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological or cytological proof of metastatic solid tumor refractory to standard therapies, or for which no standard therapies are available. Patients in the expansion cohort must have a measurable site of disease according to RECIST (v 1.0) Laboratory values must be obtained within protocol limits and obtained within 14 days prior to registration Patients must have disease which is not amenable to potentially curative surgical resection of metastatic disease (curative metastasectomy). Must be willing to provide metastatic tissue biopsy samples (may be paraffin embedded) at baseline Must be willing to undergo a metastatic tissue biopsy after 2 cycles of therapy to perform pharmacodynamic research biomarkers testing. Subjects must be willing and able to abstain from using strong or moderate CYP3A4 inhibitors or inducers during the study period. Exclusion Criteria: No symptomatic brain metastasis No prior treatment with an mTOR inhibitor or with an IGF-1R inhibitor No known history of diabetes mellitus No thrombosis or vascular ischemic events within the last twelve months No chronic treatment with systemic steroids or another immunosuppressive agent No active bleeding or a pathological condition that is associated with a high risk of bleeding No known history of HIV seropositivity No known history of Hepatitis B or Hepatitis C seropositivity No known hypersensitivity to AMG 479, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus), or to its excipients No planned immunization with attenuated live viruses during the study period
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shadia I Jalal, MD
Organizational Affiliation
Indiana University Melvin and Bren Simon Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Indiana University Melvin and Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors

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