Clinical Trial: Erythromycin Treatment for Readthrough of APC Gene Stop Codon Mutation in Familial Adenomatous Polyposis-minors' Adjusted Version

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Erythromycin Treatment for Readthrough of APC Gene Stop Codon Mutation in Familial Adenomatous Polyposis-protocol is Identical to Study No. 0519-10-TLV- Minors' Adjusted V

Brief Summary:

Colorectal cancer (CRC) is a leading cause for cancer related mortality in the western world with a lifetime risk of 6%. Etiology is complex, while genetic background significantly affects the risk. Around one third of all genetic disorders as well as most cases of Familial Adenomatous Polyposis (FAP) and a large proportion of all sporadic CRC cases occur as a result of premature nonsense mutations (creating a stop codon) in an individual's adenomatous polyposis coli (APC) gene. Nonsense mutations are single-point alterations in the DNA that prematurely halt the protein translation process, producing a shortened, nonfunctional protein. In many of these cases, if the cell can be 'persuaded' to ignore the premature stop codon signal, the resulting protein may be able to ameliorate or stop the disease.

Recently, members of the aminoglycoside family of antibiotics have been found to induce ribosomal read-through of nonsense mutations, leading to expression of a full length, functional protein. Investigators have recently shown that members of the aminoglycoside and macrolide antibiotic families can induce read-through of the nonsense mutations in the APC gene and lead to reduced oncogenic phenotypes in CRC cells and in different mice models.

The aim of this project is to determine the ability of the macrolide antibiotic-erythromycin to induce read-through of the nonsense mutations in the APC gene and to induce expression of a full length, functional APC protein in patients suffering from FAP and to tests its effect on adenoma number and size and on desmoid tumors in these patients. The future goal is to maximize the effect of stop-codon suppressors on APC while minimizing side effects.

In this study investigators will select FAP patients which carry APC nonsense mutations, trea

Detailed Summary:
Sponsor: michal roll

Current Primary Outcome:

• Evaluation of changes in number of adenomas measured by upper endoscopy [ Time Frame: After 8,16 weeks and 12 months ]
  Change in number of adenomas from baseline will be measured by endoscopic and histological evaluation. response will be tested by upper and lower endoscopies after 8 ,16-20 weeks and 12 months of treatment.
• Evaluation of changes in size of adenomas measured by lower endoscopy [ Time Frame: After 8,16 weeks and 12 months ]
  Change in number of adenomas from baseline will be measured by endoscopic and histological evaluation. response will be tested by upper and lower endoscopies after 8 ,16-20 weeks and 12 months of treatment.
• Evaluation of changes in size of desmoid tumors [ Time Frame: At the begining of the trial (before treatment) and at the end of the treatment (after 4-6 months) ]
  Desmoids imaging (US or CT or MRI) will be performed to determine the size at the begining of the study and to evaluate the change from baseline after 4-6 months of treatment.

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Tel-Aviv Sourasky Medical Center

Dates:
Date Received: January 21, 2015
Date Started: June 2015
Date Completion: December 2017
Last Updated: January 29, 2015
Last Verified: January 2015