Pancreatic cancer often is deadly because symptoms do not arise until the disease has become advanced. Less than 5 percent of pancreatic cancer patients live for five years after diagnosis. No effective treatments exist for late-stage pancreatic cancer. Cancer drugs (chemotherapy) mostly are given by mouth or intravenously (through an IV). However, it is hard to deliver high enough levels of the drug to tumors using these methods. A more direct way to deliver drugs to tumors in organs such as the pancreas is through the peritoneal cavity, the space surrounding the abdominal organs. Delivering cancer drugs by this method is called intraperitoneal (ip) chemotherapy. The investigators have developed an ip delivery method called tumor-penetrating microparticles (TPMs). TPMs are tiny particles that can be loaded with a drug, travel through the peritoneal cavity, enter a target tumor and deliver the therapy into the tumor. This project’s aim is to continue to develop this therapy to prepare it for human clinical trials. Although this version will be used to treat pancreatic cancer, the delivery method could be developed for treating a variety of other cancer types.
Pharmaceutical companies generally focus on drugs given by IV or oral administration. However, systemic therapy often does not deliver sufficient drug levels to solid tumors due to inadequate blood perfusion and high interstitial fluid pressure in tumors. On the other hand, intraperitoneal (ip) chemotherapy has demonstrated impressive survival advantage in multiple randomized trials. Due to the lack of approved ip products, these earlier studies used intravenous formulations. This approach has two limitations: (a) the restricted drug penetration to the tumor periphery diminishes the efficacy of ip treatment in patients with larger tumors, and (b) ip therapy is associated with infection due to indwelling catheter and with toxicity from high local drug levels, which produces abdominal pain. These problems have prevented widespread use of ip therapy in spite of the demonstrated efficacy. Our goal is to overcome these limitations and to address the unmet need of products suitable for ip treatments.
The investigators have developed TPMs, a first-in-class delivery system tailored to the unique anatomical properties of the peritoneal cavity. TPMs are multicomponent, multifunctional, biocompatible, biodegradable, controlled-release polymeric micron-size particles. TPMs are designed to target, penetrate and deliver pharmacodynamically optimized drug levels to the superficial and deep layers of peritoneal tumors. TPMs represent a delivery platform that can be used to deliver small molecule therapeutics, biologics, gene vectors and imaging agents. The first generation TPM, TPM001, is loaded with paclitaxel.
For patients with carcinomatosis, there are no therapeutic options and only palliative treatments (e.g., costly procedures such as repeated drainage of peritoneal fluid). The first indication for TPM001 is pancreatic cancer, which has a five-year survival rate of less than 5 percent.
Optimum Therapeutics, LLC, San Diego
Jessie L.-S. Au, Pharm.D., Ph.D.
Ze Lu, Ph.D.
Public Health Impact
The goal of this project is to develop an effective treatment for locoregional control of metastatic pancreatic cancer and, more generally, peritoneal tumors, which affect 230,000 new patients annually in the United States.
Approved studies are ongoing.
- Synthesis of Good Manufacturing Practice (GMP) material
- Formulation development
- Stability studies
- Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies
- Investigational New Drug (IND)-directed toxicology