Moffitt Opens Mesothelioma Study for Rare Cancer Subtypes

Medicine vials in a box

The Moffitt Cancer Center in Tampa has opened a mesothelioma clinical trial involving an anti-cancer enzyme drug showing unprecedented success with the most difficult disease subtypes.

Patients with sarcomatoid and biphasic histology — the most treatment-resistant subtypes of mesothelioma — can now enroll in a phase 2/3 clinical trial involving the effectiveness of ADI-PEG 20 (pegylated arginine deiminase) in combination with standard chemotherapy.

Thoracic surgeon Dr. Jacques Fontaine, director of the Mesothelioma Research and Treatment Center at Moffitt, told Asbestos.com that he and fellow investigators are hoping the mesothelioma clinical trial delivers a much-needed breakthrough for a patient population with a typically unfavorable prognosis.

“These patients have had very few treatment options in the past and were usually excluded from the trials,” Fontaine said. “This is a nice option…a first-line treatment option for these patients.”

Despite his high hopes, Fontaine, who also serves as an associate professor of surgery at the University of South Florida College of Medicine, is realistic about the possible poor outcomes of the trial.

In the past, mesothelioma patients of these subtypes have not fared well in comparison to those patients with epithelial mesothelioma, the more common subtype that responds well to treatment.

“I don’t want to overstate that this is going to be miraculous. It may be, but we don’t know that,” Fontaine said. “Hopefully, it will be good.”

UK Mesothelioma Study Sparks Optimism

Results of an earlier multicenter study of an ADI-PEG 20/chemotherapy combination in the U.K. triggered the interest of launching a trial in the U.S.

The U.K. trial involved nine patients: Four had non-small cell lung cancer, and five had advanced pleural mesothelioma.

All patients, including four with sarcomatoid or biphasic histology, achieved disease control or better results during treatment, the study showed.

“Our report describes patients with quite impressive tumor shrinkage and a disease control rate of 100 percent,” Dr. Peter Szlosarek, lead researcher at the Barts Cancer Institute in London, told Asbestos.com. “I’m excited about these results. I’ve never seen a patient response rate like this.”

The Journal of Clinical Oncology published the study results in April.

The original goal of the phase 1 study was to determine the safest, effective dosage of the drug, which researchers are also testing on patients with malignant melanoma, and prostate and renal cancers.

In the U.K. study, seven of the nine patients achieved partial response, which was seen at all dose levels.

Find Clinical Trials for Mesothelioma Patients

Get free help finding and enrolling in a mesothelioma clinical trial today!

All patients had a median overall survival of 55.7 weeks and a median progression-free survival of 30.1 weeks. Meanwhile, the mesothelioma patients in the trial had a median overall survival of 56.4 weeks and a median progression-free survival of 30.7 weeks.

“In the U.K., the median survival [with sarcomatoid subtype] is typically about four months. It’s like falling off the edge of a cliff,” Szlosarek said. “Many of these patients aren’t even offered chemotherapy because the rate of success is so low. You can usually count on one hand the number of [sarcomatoid] patients living beyond 12 months. We found our results quite interesting.”

Combining Drug with Chemotherapy Improves Treatment

U.K. researchers used the drug in conjunction with a cisplatin/pemetrexed chemotherapy combination, which will be employed in the Moffitt trial.

“By adding this drug [ADI-PEG 20], we basically can make the chemotherapy work better for these patients,” Szlosarek said.

ADI-PEG 20 binds with the amino acid arginine and depletes its effectiveness in promoting tumor growth in patients with low levels of arginine-succinate synthetase 1 (ASS1).

Mesothelioma patients with sarcomatoid and biphasic histology typically have a deficiency of ASS1.

No dose-limiting toxicities were reported in the U.K. study. Most of the adverse side effects were considered mild to moderate, and most were related to the chemotherapy, not ADI-PEG 20.

One biphasic mesothelioma patient had lived 26 months with the disease when the study was published.

Mesothelioma Clinical Trial Key to Treatment Advancements

Szlosarek has worked with ADI-PEG 20 as a cancer tool for almost two decades. He will soon be completing a larger, 31-patient study that has shown equally impressive results.

He believes the placebo-controlled study at Moffitt, which also has opened at Memorial Sloan Kettering Cancer Center in New York, will show how effective the drug can be.

The trial, which will be recruiting patients through 2018, is expected to expand soon to centers in Chicago, Houston and San Francisco.

All patients in the trial will receive the standard cisplatin/pemetrexed combination. One group also will receive the investigational drug, while the other group will receive a placebo.

“This next trial will be the ultimate test to see if this will become the new standard for these patients,” Szlosarek said. “I’m quite impressed by the activity I’ve seen.”


Tim Povtak is an award-winning writer with more than 30 years of reporting national and international news. His specialty is interviewing top mesothelioma specialists and researchers, reporting the latest news at mesothelioma cancer centers and talking with survivors and caregivers.

  1. Beddowes, E. et al. (2017, April 7). Phase I Dose-Escalation Study of Pegylated Arginine Deiminase, Cisplatin and Pemetrexed in Patients With Argininosuccinate Synthetase 1-Deficient Thoracic Cancers. Retrieved from http://ascopubs.org/doi/full/10.1200/JCO.2016.71.3230

Related News Posts

Discover Our Free Resources & Services

Learn What We Offer

Social Media

Top Authors

View our resources for patients and families

Get Help Today
Get Your Free Mesothelioma Guide