FDA Removes Clinical Hold on Study of Pancreatic Cancer Drug
Investigators evaluate recombinant hyaluronidase in patients with advanced disease
The FDA has removed its clinical hold on patient enrollment and dosing of PEGPH20 (Halozyme Therapeutics) in an ongoing phase II trial evaluating the investigational compound in patients with pancreatic cancer, permitting the study to resume under a revised protocol.
Patient enrollment is anticipated to start again after review and approval of the amended protocol by the independent review boards at the participating clinical trial sites. In May, the trial’s independent data monitoring committee recommended that enrollment and dosing in the study resume under a revised protocol.
Study 202 is a phase II randomized clinical trial evaluating PEGPH20 as first-line therapy for patients with stage-IV metastatic pancreatic cancer. The study’s primary outcome is improvement in progression-free survival in patients receiving PEGPH20 in combination with gemcitabine (Gemzar, Lilly) and nab-paclitaxel (Abraxane, Celgene Corporation) compared with those treated with gemcitabine and nab-paclitaxel alone.
After the protocol amendment, a second primary endpoint was added to assess the thromboembolic event rate in the PEGPH20 treatment arm. Secondary endpoints include the objective response rate and overall survival.
The protocol changes include the exclusion of patients who may be at increased risk of thromboembolic events. Further, low-molecular-weight heparin will be used as prophylaxis to prevent thromboembolic events. More than 100 patients are already enrolled in the trial, and a similar number of patients will be added under the revised protocol.
Certain cancers, including pancreatic, breast, colon, and prostate, have been shown to accumulate high levels of hyaluronan (HA). Aberrant accumulation of this component of the tumor’s infrastructure supports a protective network or “halo” that surrounds certain tumors. In addition, this accumulation of HA along with other matrix components increases tumor interstitial fluid pressure, thereby constricting tumor vasculature and creating a microenvironment for the growth of tumor cells compared with normal cells. Dismantling the HA component of the tumor architecture disrupts this tumor microenvironment and opens the previously constricted vessels, which may increase blood flow to the tumor. This, in turn, may allow cancer therapies to be more efficiently delivered to their target.
PEGPH20 is an investigational PEGylated form of FDA-approved subcutaneous rHuPH20 (Hylenex, Halozyme Therapeutics) that increases the half-life of the compound in the blood and allows intravenous administration.
A phase Ib study evaluated PEGPH20 in combination with gemcitabine for the treatment of patients with stage-IV metastatic pancreatic cancer. The results were presented at the 2013 American Society of Clinical Oncology (ASCO) annual meeting.
The study enrolled 28 patients with previously untreated stage-IV pancreatic ductal adenocarcinoma. The patients were treated with one of three doses of PEGPH20 (1.0, 1.6, and 3.0 mcg/kg twice weekly for 4 weeks, and then weekly thereafter) in combination with gemcitabine 1,000 mg/m2, both administered intravenously.
The overall response rate (complete response + partial response) was 42% (10 of 24 patients) for patients treated at therapeutic-dose levels of PEGPH20 (1.6 and 3.0 mcg/kg).