A Phase I Trial of AMG 386 and Temsirolimus in Advanced Solid Tumors With an Expansion Cohort in Uterine Cancer, Renal Cell Carcinoma and Carcinoid Tumors
AMG 386 is an intravenous (given by vein) drug that blocks a protein called angiopoietin. As
cancers grow they need to develop their own new blood supply to survive and this development
of new blood supply vessels is known as angiogenesis. AMG 386 works by slowing or stopping
the growth of these new blood vessels which is expected to interfere with the tumor's
ability to grow and spread to other parts of the body.
Temsirolimus is an intravenous (given by vein) drug that is commercially available and
approved for treatment of some types of kidney cancer. Temsirolimus interferes with a
protein in the cell that is part of one pathway that transmits signals to stimulate cell
growth and survival. By inhibiting this protein, called mTOR, cancer cells may stop growing
This study has two parts. The first part, called the dose escalation phase, will include
patients with any type of solid tumor (a cancer with a tissue mass) to find out the highest
dose of AMG386 and temsirolimus that can be given to patients without causing side effects
that are too severe. After this dose is found, another group of patients that take part in
the study will receive this dose in the second phase called the dose expansion phase. The
dose expansion phase of the study will only include patients that have recurrent (the cancer
has come back) or metastatic uterine, renal cell, and carcinoid tumors.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose (RP2D) and safety profile of AMG 386 in combination with temsirolimus in patients with advanced solid tumors.
The recommended phase II dose is defined as <1 out of 6 at highest dose level below the maximally administered dose. The safety profile will include the number of participants who experience an adverse event, description of adverse events, grade of events, relationship to the drugs, and frequency of events.
Philippe Bedard, M.D.
Princess Margaret Cancer Centre
Canada: Ethics Review Committee
PJC-008 (NCI 9041)