MILAN – An ongoing phase III trial launched in 2012 that is testing whether adjuvant therapy aids women following removal of high-risk uterine leiomyosarcomas has also blazed a path for the International Rare Cancer Initiative, which has launched two other trials in rare cancers and is planning to start several more.

The advanced uterine leiomyosarcoma trial, which is testing an adjuvant regimen of up to four courses of gemcitabine (Gemzar) plus docetaxel (Taxotere) followed by doxorubicin (Adriamycin) for four courses should "answer the adjuvant chemotherapy question" for these patients, Dr. Martee L. Hensley said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology.

The trial, known as Gynecologic Oncology Group (GOG) 0277, was the first study organized by the International Rare Cancer Initiative (IRCI) to activate. The study involves more than 200 U.S. centers and will open in many more European centers once regulatory approvals occur, said Dr. Hensley, professor of medicine at Weill Cornell Medical College and a gynecologic medical oncologist at Memorial Sloan- Kettering Cancer Center, New York.

Oncologists diagnose about 1,200 uterine sarcomas annually in the United States, most of which are uterine-limited and histologically high grade. "Successful conduct of this study in this rare but high-risk disease will establish the standard of care for managing women who have undergone complete resection," she said in an interview.

"Conducting prospective randomized trials in rare cancers is a significant challenge. International collaboration is considered a key factor in success" by speeding patient accrual, identifying research questions of international importance, and designing a trial that is internationally accepted and generalizable, Dr. Hensley said. In 2011, five cancer organizations formed the IRCI: the U.S. National Cancer Institute, the European Organization for the Research and Treatment of Cancer, Cancer Research UK, the U.K. National Cancer Research Network, and the French Institut National du Cancer.

The IRCI defines rare cancers as generally having an incidence below 2 cases per 100,000 population, and it is charged to develop intervention trials for these cancers, especially randomized trials.

"Creation of the IRCI has provided some needed infrastructure and has been critical to the success of GOG 0277," Dr. Hensley said. "But one could also say that GOG 0277 is also key to the IRCI’s success. The work we have done for GOG 0277 will inform the design and conduct of future international studies" in rare cancers.

The IRCI includes nine committees, each of which develops trials for different rare-cancer types. These include the gynecologic sarcoma committee that Dr. Hensley serves on and which helped organize GOG 0277, and other committees for small bowel adenocarcinoma, salivary gland cancer, thymoma, ocular melanoma, relapsed or metastatic anal cancer, rare brain cancer, desmoplastic small-round-cell tumor, and penile cancer. The committees include representatives appointed by the founding organizations, which also appoint the members of the IRCI board, the body that determines which committees to form, explained Nicola Keat, a staffer at Cancer Research UK in London who serves as the IRCI coordinator.

The gynecologic sarcoma committee decided that the question of whether adjuvant chemotherapy following complete resection helps patients with uterus-limited, high-grade leiomyosarcoma had "primary importance," said Dr. Hensley. "We recognized that the IRCI provided an ideal opportunity."

The gynecologic sarcoma group also plans to open a prospective study of doxorubicin for chemotherapy-naive patients with advanced, high-grade undifferentiated sarcoma of the uterus, a rare and aggressive cancer with no standard treatment. The study would also assess whether cabozantinib (Cometriq) can further prolong progression-free survival, compared with placebo, in patients with stable disease or an objective response to doxorubicin. In addition, the committee would like to launch a trial of aromatase inhibition for patients with low-grade endometrial stromal sarcoma through the IRCI, she said.

Following the launch of GOG 0277, the IRCI opened enrollment of patients into a trial focused on advanced uveal melanoma at U.S. centers, with U.K. recruitment anticipated to start later this year, Ms. Keat said in an interview. A third IRCI-organized trial, for patients with advanced anal cancer, recently opened for enrollment at participating U.K. centers, she added.

GOG 0277 began in June 2012 and aims to enroll 216 patients. As of February 2014, it had accrued seven patients, but Dr. Hensley said she believed the study was on track to its targeted finish date in 2018, as patients will soon start to enroll in Europe. "We expect the study to open in the U.K. in the next couple of months," Ms. Keat said in late March.

Dr. Hensley said that her spouse is a Sanofi employee. Ms. Keat had no disclosures.

mzoler@frontlinemedcom.com

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Launch of rare-cancer trial spurs many more