Kimberlea Sheldon, a school-bus driver from Duvall, reaches for a vial of nose drops three times each day. It's not to relieve springtime allergy symptoms.
Sheldon is self-administering her chemotherapy for ovarian cancer. Sheldon is taking part in a nationwide clinical trial led by the Hutch's Puget Sound Oncology Consortium to evaluate the safety and efficacy of combining standard initial chemotherapy for ovarian cancer with IM862, a drug that appears to have cancer-fighting properties.
The trial was developed through the collaborative efforts of the Hutch Clinical Research Division and the Gynecologic Oncology Department at University of Washington School of Medicine.
Dr. Leona Holmberg, an investigator in the Clinical Research Division, and Dr. Pamela Paley, a UW gynecological oncologist, direct the Phase II study, which will treat 180 women at 15 medical centers across the country.
Pre-clinical research suggests that IM862, in a process called angiogenesis, stimulates the body's immune system and inhibits the development of blood vessels needed by tumors to grow and metastasize. Due to its apparent immune-stimulating and angiogenesis-inhibiting properties, the addition of IM862 may reduce blood vessels that feed tumor cells, as well as increase the ability of the patient's immune system to kill his or her cancer, Paley said.
As a Phase II clinical trial, the study has a primary objective to determine the safety of IM862 when given with chemotherapy as well as to answer whether the addition of IM862 increases the percentage of patients with no evidence of disease during follow-up surgery after completing initial chemotherapy. Historically, about half of patients with stage III cancer show evidence of disease at that time.
Secondary objectives include evaluation of occurrence of infection or other complications, length of remission and the ability of IM862 to decrease tumor blood supply and stimulate the immune system.
Patients self-administer the drug, which is dispensed as nose drops and is quickly absorbed into the bloodstream through the mucous membranes. IM862 has been tested in clinical trials involving more than 400 cancer patients and has demonstrated a favorable safety profile with generally mild side effects.
"I know how the other chemotherapy I'm getting makes me feel," said Sheldon, who is in good health after two months of treatment, "but I haven't noticed any side effects from the IM862."
About 27,000 new cases of ovarian cancer are detected each year in this country, and about 15,000 women die annually from the disease. Because no reliable means of early detection exists, most cases are diagnosed at an advanced stage. While the majority of women with stage III ovarian cancer initially achieve complete remission with surgery and standard chemotherapy, many patients relapse with time.
Patients eligible to participate in the study have been diagnosed with stage III disease, have undergone surgery to remove cancerous tissue and have not yet received other treatment for ovarian cancer. Participants are randomized to receive one of three doses of IM862 in conjunction with paclitaxel and carboplatin, described by Homberg as the "gold standard of chemotherapy for ovarian cancer." The trial is double-blinded so neither patient nor physician will know which dose of study drug the patient is receiving.
"After six cycles of chemotherapy, patients with no clinical evidence of disease will undergo 'second look' surgery," Holmberg said. "We'll be looking for no evidence of the disease, macroscopic or microscopic traces of cancer."
Patients with no trace or only microscopic traces of the disease will then be treated solely with IM862 for an additional 24 weeks.
"Our hope is that the combination of IM862 and chemotherapy will result in a larger number of women with ovarian cancer achieving long-term remission from their disease with little or no additional toxicity," Paley said.
IM862, manufactured by Cytran, Inc. of Kirkland, Wash., is a synthesized version of a naturally occurring small protein, or peptide, that is made up of two amino acids - the building blocks of proteins.
Preliminary data indicate that the drug has multiple mechanisms of action, including stimulation of the immune system and suppression of cell-signaling proteins (cytokines), resulting in both inhibition of angiogenesis and direct attack on the tumor.
In previous studies, IM862 has been shown to be a useful therapy for Kaposi's sarcoma, a cancer predominantly affecting AIDS patients. The drug is also undergoing clinical trials for the treatment of melanoma and prostate, colorectal and renal cancers.
Holmberg said that in addition to clinical follow-up, the study will include a laboratory component.
"We'll be conducting a correlate study to examine whether levels of markers for angiogenesis are affected by IM862," she said. "In addition, we'll be measuring the tumor-killing abilities of the immune systems of patients treated with the drug."