Spots Global Cancer Trial Database for A Trial of AMG 479, Everolimus (RAD001) and Panitumumab in Patients With Advanced Cancer - QUILT-3.007

Study Description

Brief Summary: This open-label, non-randomized, dose escalation phase I biomarker trial of the triplet regimen of AMG 479, everolimus, and panitumumab for subjects with refractory advanced solid tumors is designed to assess the safety and tolerability of this combination as well as preliminary efficacy.

Detailed Description: The purpose of this study is to find the safest dose of the drugs AMG 479 and everolimus in combination and then with panitumumab added. This study will consist of two parts. If you are enrolled in Part One of the study, you will receive AMG 479 and everolimus. If you are enrolled in Part Two of the study, you will receive AMG 479, everolimus, and panitumumab. The study will also look at how the drugs work in the body, and will see if there is any effect on your cancer. The study will have two parts: The first part will be to define the MTD/RPTD of the doublet combination of AMG 479 + everolimus using a standard 3-6 subjects per dose level. Since each agent is known to be well tolerated as monotherapy, we will start with the full dose of AMG 479 and escalate the dose of everolimus. Once the RPTD is established, an additional 20 subjects will be added to confirm the tolerability of this regimen and to allow more detailed biomarker assessment for the effect of each agent alone in the doublet combination. In this biomarker expanded cohort, subjects will start treatment with 2 weeks of AMG 479 monotherapy (a single dose of AMG 479), followed by the combination of AMG 479 + everolimus on day 15. The second part of the study will assess tolerability of the triplet therapy, with panitumumab added to the RPTD of AMG 479 + everolimus, again using a standard cohort size of 3-6 subjects. Finally, at the recommended phase II dose of the triplet therapy, 20 subjects will be added to an expanded safety and biomarker cohort. In this biomarker expanded cohort, 10 subjects will start treatment with two weeks of AMG 479 monotherapy (a single dose of AMG 479), and 10 subjects will start treatment with two weeks of everolimus monotherapy, with all subjects starting the triplet combination therapy with panitumumab on day 15. Two sustained complete responses (one \> 2 years of complete response, second \>8 months of complete response) were seen in subjects with refractory NSCLC (never smokers) enrolled in the doublet regimen. Therefore, an additional 20 subjects with NSCLC, never smokers or non-smokers with ≤ 10 year pack smoking history will be enrolled at MTD/RPTD to further assess safety, tolerability and clinical activity in this specific patient cohort. In this cohort, subjects will start both drugs on cycle 1, day 1. ABOUT THE STUDY DRUGS: AMG 479 is an intravenous (I.V., meaning through a vein) medication made from a special type of human protein called antibodies. AMG 479 blocks the activity of another protein called IGF-1R which is important for tumors to grow. Blocking IGFR-1 activity has been shown to slow or kill cancer cells in laboratory studies. AMG 479 is currently being evaluated in clinical research studies in a variety of cancers. AMG 479 is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of cancer and is therefore considered an investigational drug. Everolimus is a pill that works by blocking the activity of a substance in the body known as mTOR (mammalian target of rapamycin). mTOR is important for helping the growth and survival in normal and cancer cells. Blocking mTOR activity has been shown to slow or kill cancer cells in laboratory studies. Everolimus is currently being evaluated in clinical research studies in a variety of cancers. Everolimus (AfinitorTM) is approved by the FDA for the treatment of advanced renal cell carcinoma (kidney cancer), subependymal giant cell astrocytoma (a type of brain cancer), neuroendocrine tumors originating in the lung or gastrointestinal (GI) tract, and HER2-negative breast cancer. Besides cancer, everolimus also has been tested for its ability to help block the rejection of solid organs transplants (such as liver or kidney transplants). Everolimus is approved for this purpose in Europe but not in the United States. Panitumumab is another intravenous (I.V.) medication made from a special type of human protein called antibodies. Panitumumab blocks the activity of a protein called EGFr which is also important for tumors to grow. Blocking EGFr activity has been shown to slow or kill cancer cells in laboratory studies. Panitumumab is currently being evaluated in clinical research studies in a variety of cancers. Panitumumab (Vectibix™) is approved by the FDA for the treatment of advanced colorectal cancer following 5'FU, oxaliplatin and irinotecan chemotherapy regimens.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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