Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01122199

First Posted: May 13, 2010

Last Update Posted: May 10, 2017

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborators:

Amgen

Novartis

Information provided by (Responsible Party):

Shadia Jalal, Indiana University School of Medicine

Purpose

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.

Condition	Intervention	Phase
Neoplasm Metastases	Drug: RAD001 + AMG479	Phase 1


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors

Resource links provided by NLM:

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Shadia Jalal, Indiana University School of Medicine:

Primary Outcome Measures:

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 ]
To evaluate the grade and severity of adverse events as a measure of safety and toxicity [ Time Frame: 2 years ]

Secondary Outcome Measures:

To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors [ Time Frame: 5-10 years ]
response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS)


Enrollment:	27
Actual Study Start Date:	May 14, 2010
Study Completion Date:	January 19, 2015
Primary Completion Date:	January 19, 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Open Label RAD001+ AMG479	Drug: RAD001 + AMG479 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. Other Name: everolimus + ganitumab

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.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01122199

Locations


United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Shadia Jalal

Amgen

Novartis

Investigators


Study Chair:	Shadia I Jalal, MD	Indiana University Melvin and Bren Simon Cancer Center

More Information


Responsible Party:	Shadia Jalal, Assistant Professor of Medicine, Indiana University School of Medicine
ClinicalTrials.gov Identifier:	NCT01122199 History of Changes
Other Study ID Numbers:	1002-16; IUCRO-0287
First Submitted:	May 7, 2010
First Posted:	May 13, 2010
Last Update Posted:	May 10, 2017
Last Verified:	May 2017

Additional relevant MeSH terms:


Neoplasm Metastasis Neoplastic Processes Neoplasms Pathologic Processes Everolimus Sirolimus Antibodies, Monoclonal Antineoplastic Agents	Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents

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