Know Cancer

or
forgot password

Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Neoplasm Metastases

Thank you

Trial Information

Phase I Study of mTOR Inhibitor RAD001 in Combination With IGF-1R Inhibitor AMG479 for Patients With Advanced Solid Tumors


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated (MTD) and recommended Phase II doses for AMG479 and RAD001 in patients with refractory solid tumors

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Shadia I Jalal, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Indiana University Melvin and Bren Simon Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

1002-16; IUCRO-0287

NCT ID:

NCT01122199

Start Date:

June 2010

Completion Date:

June 2014

Related Keywords:

  • Neoplasm Metastases
  • Neoplasms
  • Neoplasm Metastasis

Name

Location

Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289