Targeting a Common Characteristic of Advanced Tumors
Name of the Trial
Phase I Pilot Study of Topotecan in Patients With Metastatic or Unresectable Solid Tumors Expressing Hypoxia Inducible Factor-1a (HIF-1a) (NCI-05-C-0186). See the protocol summary.
Dr. Shivaani Kummar and Dr. Giovanni Melillo, NCI Center for Cancer Research.
Why This Trial Is Important
Hypoxia is a state of oxygen deficiency that can develop in tumors when they outgrow their blood supply. When this condition develops, tumors must adapt to the new hypoxic environment in order to survive and keep growing. A protein called hypoxia inducible factor-1a (HIF-1a) helps tumor cells (and normal cells) adapt to hypoxic conditions by activating genes needed for cell survival, resistance to apoptosis (programmed cell death), and the growth of new blood vessels (angiogenesis). Cancer cells may also produce HIF-1a as a result of genetic changes not related to hypoxia. Many solid tumors overproduce HIF-1a, and high levels of this protein have been associated with tumor aggressiveness and resistance to treatment.
The FDA-approved chemotherapy drug topotecan is one of only a few agents that have shown the ability to inhibit HIF-1a in laboratory studies. Animal studies conducted by Dr. Melillo and his colleagues suggest that giving topotecan at lower doses over a longer period of time can reduce the level of HIF-1a in tumors and inhibit angiogenesis.
In this trial, doctors are testing the ability of topotecan to inhibit HIF-1a production and prevent tumors from growing and spreading further.
"HIF-1a gives tumors a selective growth advantage," said Dr. Kummar. "We're hoping to exploit a novel characteristic of an FDA-approved drug to take away this selective advantage and cause tumors to stop growing."
Who Can Join This Trial
Researchers seek to enroll 20 patients aged 18 or over with metastatic or unresectable solid tumors expressing HIF-1a for which standard therapy either has not been effective or does not exist. See the list of eligibility criteria.
Study Site and Contact Information
This study is taking place at the NIH Clinical Center in Bethesda, Md. For more information, call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.