Study of RAD001 + AMG479 for Patients With Advanced Solid Tumors
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Purpose
| 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 |
- 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 ]
- 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: | December 2016 |
| Primary Completion Date: | February 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 (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01122199
| United States, Indiana | |
| Indiana University Melvin and Bren Simon Cancer Center | |
| Indianapolis, Indiana, United States, 46202 | |
| Study Chair: | Shadia I Jalal, MD | Indiana University Melvin and Bren Simon Cancer Center |
More Information
Additional 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 |
| Study First Received: | May 7, 2010 |
| Last Updated: | April 15, 2016 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
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 |
ClinicalTrials.gov processed this record on September 26, 2016