MENLO PARK, Calif--Matrix Pharmaceutical, Inc. has begun phase III clinical testing of its IntraDose-CDDP injectable gel (see image) for treatment of recurrent head and neck cancer and other accessible tumors.
MENLO PARK, Calif--Matrix Pharmaceutical, Inc. has begun phaseIII clinical testing of its IntraDose-CDDP injectable gel (seeimage) for treatment of recurrent head and neck cancer and otheraccessible tumors.
IntraDose-CDDP is a site-specific injectable therapy designedto provide localized, sustained release of high concentrationsof cisplatin directly within the tumor, with decreased systemictoxicity.
"The start of this phase III program is a significant advancein Matrix's oncology program," Craig R. McMullen, presidentand CEO, told Oncology News International.
In a phase II trial presented last year at the American Societyof Clinical Oncology (ASCO) meeting, 34 (48%) of 71 evaluablesolid tumors exhibited a complete response to IntraDose-CDDP,and no significant adverse reactions were seen. The study included31 patients with recurrent or refractory disease.
"We were particularly encouraged to note that an even greaternumber of complete responses was seen in tumors of patients withadenocarcinoma (81%) and squamous cell carcinoma (59%),"Mr. McMullen said.
The head and neck portion of the phase III program consists oftwo randomized, double-blind, placebo-controlled studies of patientswith recurrent squamous cell carcinoma. One trial will be conductedin Europe, with clinical sites in Great Britain, Germany, andHolland, while an identical trial will take place at sites inthe United States. Approximately 90 patients will be enrolledin each study.
Two separate open-label trials of patients with accessible solidtumors will be conducted in the United States and Europe withapproximately 60 patients in each trial. Tumors that may be treatedin this study include recurrent cases of breast cancer, malignantmelanoma, lung cancer, sarcoma, and colorectal cancer.
Mr. McMullen believes that the treatment could be developed asa cost-effective outpatient procedure, minimizing the hospitalization,ancillary treatments, and supportive care routinely associatedwith systemic chemotherapy.
Matrix's IntraDose products are comprised of a biodegradable proteinmatrix (purified bovine collagen), to sustain the rate of drugrelease; a chemotherapeutic agent; and the vasoconstrictor epinephrine,which acts as a "chemical tourniquet" to further holdthe drug within the tumor site.
IntraDose-CDDP has also been tested in patients with primary andmetastatic liver cancer, delivered directly into the tumor underthe guidance of computed tomography (CT).
Phase I/II data presented last year at ASCO showed greater than60% necrosis in 18 of 20 treated liver tumors, eight of whichdemonstrated greater than 90% necrosis. Again, there were no medicallysignificant adverse effects. Advanced studies in this settingare planned for 1996.
The company has also recently begun phase II testing of IntraDose-CDDPin prostate cancer. The agent is injected directly into the prostateunder transrectal ultrasound guidance. In this trial, patientswho have been scheduled for prostatectomy will receive three IntraDose-CDDP intraprostatic treatments. Afterwards, the excised prostateswill be evaluated to determine drug distribution, safety, andeffectiveness.
Matrix has completed phase III studies of its dermatologic product,AccuSite Injectable Gel (fluorouracil and epinephrine), for thetreatment of genital warts, and expects to submit a new drug application(NDA) to the FDA for that indication later this year.
International phase III trials of AccuSite in patients with basalcell cancer have also begun. The company believes the productmay provide a tissue-conserving alternative to surgical removalof such lesions.