PhytoCeutica, Inc.

The aim of this research project is to determine the amount of capecitabine (Xeloda) which can be given safely with PHY906 (investigational drug) on a novel schedule. It is also the aim of this research project to determine what the effects, good and/or bad, are of combining capecitabine (Xeloda) with PHY906 (investigational drug) in the treatment of advanced pancreatic cancer.
PHY906 is a powder from plants sold as a health food supplement in the United States. PHY906 has been used in China, Taiwan and other Asian countries as traditional Chinese medicine for hundreds of years.
The other drug involved in this study, capecitabine is an oral form of chemotherapy already approved by FDA in the management of colorectal and breast cancer.
Laboratory studies in animal models have shown that the combination of capecitabine and PHY906 shrinks liver cancer, and a pilot clinical study is currently evaluating this combination in patients with liver cancer to define the benefit. PHY906 has also shown to decrease diarrhea related to chemotherapy in a small study performed in patients with colon cancer treated at the Yale Cancer Center. Our recent laboratory studies have also shown that the combination of capecitabine and PHY906 also shrink pancreatic tumors in mouse models. This prompted us to test the combination of capecitabine and PHY906 in patients with advanced pancreatic cancer to assess the benefit in survival as well as any decrease in side effects, such as diarrhea caused by capecitabine.

Capecitabine is a chemotherapeutic that has been approved for use in breast and colorectal cancers. The advantages of capecitabine are that (1) it is an oral drug; and (2) it is less toxic than many other chemotherapeutics. In an off-label hepatocellular carcinoma (HCC) clinical study, the response rate with capecitabine was 13%. The botanical drug PHY906--currently manufactured pursuant to GMP standards and regulations--has been used in China for over 1800 years to treat gastrointestinal-related ailments. Recently, preclinical studies demonstrated that PHY906 potentiates the anti-tumor effect of capecitabine. This trial will evaluate the safety and efficacy of PHY906 in enhancing the anti-tumor effects of capecitabine.

The triple combination chemotherapy of irinotecan, 5-fluorouracil and leucovorin (CPT-11/5-FU/LV or Saltz regimen) is the treatment of choice for patients with advanced colorectal cancer. Severe diarrhea, unfortunately, is a side effect of such treatment. Preclinical studies have indicated that the botanical drug PHY906 can reduce such diarrhea without compromising the effectiveness of the chemotherapy. The primary purpose of this clinical study is to evaluate the safety, tolerability and minimum effective dose of PHY906 when administered in conjunction with the Saltz regimen.