Cancers of the ovary, colon, stomach, and appendix often spread throughout the abdomen and pelvis. The process, known as peritoneal carcinomatosis, is a rare, terminal disease with a median survival of six months. Since the majority of patients have limited therapeutic options and frequently succumb to bowel obstruction, subsequent malnutrition and death, innovative approaches to this disease are necessary.
Throughout his career, John Stewart IV, MD, MBA, associate director of clinical research at the University of Illinois Cancer Center, has focused on viruses that effectively initiate the killing of tumor cells and induce robust and durable anti-tumor immune responses. These oncolytic viruses are considered by many to be a much needed approach to a variety of cancers.
The University of Illinois Cancer Center currently serves as a recruitment site for Stewart’s Phase I Trial of Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies (TEMPO). The trial seeks to evaluate the toxicity profile of intraperitoneal talimogene laherparepvec, a modified herpes virus. It also produces granulocyte-macrophage colony stimulating factor in patients with measurable stage IV peritoneal surface dissemination of gastrointestinal or recurrent, platinum-resistant ovarian cancer on radiographic imaging that cannot be completely resected at the time of abdominal exploration or elevated CEA/CA-125 as markers of the disease.
The trial will be conducted in two stages: A Dose Escalation Cohort, and a Dose Expansion Cohort. All patients will receive an initial seroconversion dose of talimogene laherparepvec on the first day of Cycle 1 to enable seroconversion as described in the currently approved treatment protocol for the treatment of cutaneous melanoma. Three weeks after the seroconversion dose, patients will receive talimogene laherparepvec at the dose level for the cohort in which they are enrolled.
Patients will be treated every two weeks with up to four doses. The first cycle consists of five weeks, with subsequent cycles lasting two weeks. Up to three dose levels will be explored in a standard ‘3+3’dose escalation design in the Dose Escalation Cohort. Three subjects will be accrued at the starting dose level. If no DLTs (Dose-Limiting Toxicity) are seen at that level, three subjects will be enrolled at the next dose level. Should one of the three subjects have a DLT at any dose level, an additional three subjects will be enrolled at that dose level. If one of six subjects experience DLT, escalation may continue.
If two or more subjects have DLT at any dose level, that dosage will be considered to have unacceptable toxicity; the next lower dose level will then have additional subjects enrolled. Up to six subjects will be enrolled at the maximum tolerated dose before proceeding to the expanded cohort. The Dose Expansion cohort will enroll subjects at the maximum tolerated dose and follow the treatment scheme described above.
Patients who complete treatment without documented disease progression will have disease status (blood tumor marker(s) and restaging scans every 12 weeks) followed until the disease progresses or the beginning of a new anti-cancer treatment regimen. The disease status may be collected by personal interviews or through the review of medical records. Participants will be followed for progression every 12 weeks or as indicated until the disease progression, or the start of a new anti-cancer therapy. Upon completion of the treatment, subjects will be monitored for survival for up to two years.