Mithramycin for Children and Adults With Solid Tumors or Ewing Sarcoma

Summary

Background: \- Mithramycin is a drug that was first tested as a cancer therapy in the 1960s. It acted against some forms of cancer, but was never accepted as a treatment. Research suggests that it may be useful against some solid tumors, particularly Ewing sarcoma. Researchers want to see if mithramycin can be used to treat solid tumors in children and adults. It will be tested in different groups of people, including those with a type of Ewing sarcoma that contains a chemical called Ewings sarcoma - friend leukemia integration 1 transcription factor (EWS-FLI1). Objectives: \- To see if mithramycin is safe and effective against solid tumors and Ewing sarcoma in children and adults. Eligibility: * Children and young adults between 1 and 17 years of age with solid tumors that have not responded to standard treatment. * Adults at least 18 years of age with EWS-FLI1 Ewing sarcoma that has not responded to standard treatment. * Children and young adults between 1 and 17 years of age with EWS-FLI1 Ewing sarcoma that has not responded to standard treatment. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor tissue samples will be used to monitor the cancer before treatment. Individuals with solid brain tumors will not be eligible. * Participants will receive mithramycin every day for 7 days, followed by 14 days without treatment. Each 28-day round of treatment is called a cycle. * Treatment will be monitored with frequent blood tests and imaging studies. * Participants will continue to take the drug for as long as the side effects are not severe and the tumor responds to treatment.

Timeline

Start

2012-05-10

Primary completion

2014-05-21

Completion

2014-05-21

Outcome

Outcome not reported

Stopped (Enrollment): “Study was closed to enrollment before dose level one was completed.”

Publications

• Background Esiashvili N, Goodman M, Marcus RB Jr. Changes in incidence and survival of Ewing sarcoma patients over the past 3 decades: Surveillance Epidemiology and End Results data. J Pediatr Hematol Oncol. 2008 Jun;30(6):425-30. doi: 10.1097/MPH.0b013e31816e22f3.
• Background Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, Turc-Carel C, Triche TJ, et al. The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med. 1994 Aug 4;331(5):294-9. doi: 10.1056/NEJM199408043310503.
• Background Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992 Sep 10;359(6391):162-5. doi: 10.1038/359162a0.
• Results Grohar PJ, Glod J, Peer CJ, Sissung TM, Arnaldez FI, Long L, Figg WD, Whitcomb P, Helman LJ, Widemann BC. A phase I/II trial and pharmacokinetic study of mithramycin in children and adults with refractory Ewing sarcoma and EWS-FLI1 fusion transcript. Cancer Chemother Pharmacol. 2017 Sep;80(3):645-652. doi: 10.1007/s00280-017-3382-x. Epub 2017 Jul 22.

Drugs

Indications