Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Indiana University
Sponsor:
Collaborators:
Amgen
Novartis
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01122199
First received: May 7, 2010
Last updated: May 30, 2014
Last verified: May 2014
  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: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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:


Further study details as provided by Indiana University:

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

Secondary Outcome Measures:
  • To determine preliminary antitumor efficacy of AMG479 and RAD001 in solid tumors [ Time Frame: 5-10 years ] [ Designated as safety issue: No ]
    response and stable disease rates, duration of response and of stable disease, time to progression (TTP) and overall survival (OS)


Estimated Enrollment: 30
Study Start Date: June 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01122199

Contacts
Contact: Anne Younger, RN 317-274-0951 anefoste@iupui.edu
Contact: Shadia I Jalal, MD 317-274-3589 sjalal@iupui.edu

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Anne Younger, RN    317-274-0951    anefoste@iupui.edu   
Contact: Shadia I Jalal, MD    317-274-3589    sjalal@iupui.edu   
Principal Investigator: Shadia I Jalal, MD         
Sponsors and Collaborators
Indiana University
Amgen
Novartis
Investigators
Study Chair: Shadia I Jalal, MD Indiana University Melvin and Bren Simon Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01122199     History of Changes
Other Study ID Numbers: 1002-16; IUCRO-0287
Study First Received: May 7, 2010
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014