- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01122199
Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors
Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University Melvin and Bren Simon Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Open Label
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
1 year
|
To evaluate the grade and severity of adverse events as a measure of safety and toxicity
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
5-10 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Shadia I Jalal, MD, Indiana University Melvin and Bren Simon Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1002-16; IUCRO-0287
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neoplasm Metastases
-
Rutgers, The State University of New JerseyRecruitingPalliative Dose Escalated Radiation for Painful Non-Spine Bone Metastases and Painful Non-Bone MetasMetastases, Neoplasm | Neoplasm MetastasesUnited States
-
Azienda Ospedaliera di PadovaIstituto Oncologico Veneto IRCCSRecruitingColorectal Adenocarcinoma | Colorectal Liver Metastases | Unresectable Malignant NeoplasmItaly
-
University of CalgaryNot yet recruitingBone Metastases | Spine Metastases | Bone LesionCanada
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedBone Metastases | Cancer Survivor | Metastatic Malignant Neoplasm in the BoneUnited States
-
Betta Pharmaceuticals Co., Ltd.Recruiting
-
Shanghai Changzheng HospitalNot yet recruiting
-
Chinese University of Hong KongNot yet recruitingBone Metastases
-
University Hospital, GhentFlemish institute of biotechnology (VIB)RecruitingPeritoneal MetastasesBelgium
-
National Taiwan University HospitalRecruiting
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Accuray IncorporatedRecruiting
Clinical Trials on RAD001 + AMG479
-
Children's Hospital Medical Center, CincinnatiNovartisCompletedTuberous Sclerosis | AngiolipomaUnited States
-
Novartis PharmaceuticalsCompletedMetastatic Renal Cell Carcinoma (mRCC)Germany
-
University of Alabama at BirminghamNational Cancer Institute (NCI); Children's Hospital of Philadelphia; Washington... and other collaboratorsCompleted
-
Novartis PharmaceuticalsCompleted
-
Novartis PharmaceuticalsCompletedLymphangioleiomyomatosis (LAM) | Tuberous Sclerosis Complex (TSC)United States, United Kingdom, Germany, Italy, Russian Federation, Netherlands, Japan, Canada, Poland, France, Spain
-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI); NRG OncologyCompletedBrain and Central Nervous System TumorsUnited States, Israel, Canada
-
University of ChicagoNovartis PharmaceuticalsTerminatedNon-Small Cell Lung CancerUnited States
-
Guangdong Provincial People's HospitalNovartisUnknownNeuroendocrine Tumors | Carcinoid TumorChina
-
Fox Chase Cancer CenterRecruitingMetastatic Pancreatic CancerUnited States
-
National Cancer Institute (NCI)TerminatedRhabdomyosarcoma | Rhabdomyosarcoma, Alveolar | Rhabdomyosarcoma, EmbryonalUnited States