|
|
|
|
For ACC patients with progressive disease, there has been a flurry of activity in clinical trials to consider. In all cases, patients should consult with a trusted physician to determine whether a study may be appropriate. Open clinical trials that are recruiting patients are listed on ACCRF's
Current Studies webpage.
AL101 Notch Inhibitor Study in ACC
ACCRF grantee
Dr. Renata Ferrarotto of MD Anderson and her colleagues
identified a subset of ACC patients whose tumors have genetic alterations that activate NOTCH genes, which are associated with more aggressive disease. Fortunately, the first phase II clinical trial of a NOTCH inhibitor for ACC patients recently opened. Only ACC patients with activating mutations in the NOTCH1, NOTCH2, NOTCH3 or NOTCH4 genes are eligible, as determined by a tumor profiling report. It is estimated that perhaps 20-25% of recurrent/metastatic ACC patients have tumors with NOTCH mutations. More information about the study is available at
https://www.clinicaltrials.gov/ct2/show/NCT03691207.
The following sites in the USA and Canada are currently involved, although European and Asian sites may open next year if the preliminary results are promising.
|
Primary Investigator
|
Center Name
|
City
|
Opening Date
|
|
|
Honor Health
|
Scottsdale, AZ, USA
|
October 2018
|
|
|
MD Anderson Cancer Center
|
Houston, TX, USA
|
November 2018
|
|
|
Massachusetts General Hospital
|
Boston, MA, USA
|
December 2018
|
|
|
Memorial Sloan Kettering CC
|
New York, NY, USA
|
December 2018
|
|
|
Fred Hutchinson Cancer Center
|
Seattle, WA, USA
|
January 2019
|
|
|
Tom Baker Cancer Center
|
Calgary, AB, Canada
|
January 2019
|
|
|
Moffitt Cancer Center
|
Tampa, FL, USA
|
February 2019
|
|
|
Sylvester Cancer Center
|
Miami, FL, USA
|
February 2019
|
|
|
London Health Sciences Center
|
London, ON, Canada
|
February 2019
|
|
|
Juravinski Cancer Center
|
Hamilton, ON, Canada
|
TBD
|
|
|
University of Southern California
|
Los Angeles, CA, USA
|
TBD
|
MYB DNA Vaccine Study in ACC (MYPHISMO)
The vast majority of ACC cases are thought to be caused by over-activation of the MYB gene, sometimes in concert with other genes such as NOTCH. ACCRF has supported the efforts of
Dr. Rob Ramsay at the Peter Mac Cancer Centre in Melbourne, Australia, to open the first clinical trial of a therapy that directly targets MYB. The study combines a MYB DNA vaccine with a PD-1 immune checkpoint inhibitor to treat patients with ACC or colorectal cancer. The first ACC patient received her first infusion of the MYB DNA vaccine in September.
Immune Checkpoint Inhibitor Studies
ACC tumors generally do not attract the attention of the immune system, as noted by ACCRF grantee
Dr. Jonathan Schoenfeld in his
study of immunologic markers in ACC. Therefore, clinical researchers have attempted to activate the immune system to attack ACC by combining immune checkpoint inhibitors with other therapies:
Recently, Dana Farber stopped enrolling patients into the first study (radiation combination) until an interim assessment is completed. For the Nivolumab/Ipilumumab studies, Northwestern continues to enroll patients but Memorial Sloan Kettering has completed enrollment. Over the next year, as clinical trial results are reported, we expect to learn a great deal about which ACC patients may benefit from immune checkpoint inhibitors.
|
|
|
ACCRF's global network of researchers continues to press forward with important scientific advances. Two recent publications are of particular note.
ACC Cell Line
Tumor cells that grow in plastic dishes (cell lines) are very useful for cancer researchers in understanding the molecular basis of a tumor type and for discovering drugs that may be effective. For the past dozen years, ACCRF has supported many researchers to develop ACC cell lines that maintain the key features of ACC with no luck...until now.
Drs. Jaques Nor and Kristy Warner at the University of Michigan carefully coaxed ACC tumor cells to grow indefinitely in plastic dishes using a modified blend of supportive ingredients. Importantly, their cell line did not lose over time the MYB-NIFB fusion that is characteristic of ACC tumors, an accomplishment that has evaded all previous researchers. The pivotal work is described in this Oral Oncology
journal article.
The new cell line, UMHACC-2A, will permit high-throughput genetic and drug screens that have not been possible in ACC before, aiding both target and drug discovery. Such studies will be even more valuable if more cell lines are developed that reflect the full diversity of ACC patients' tumors. Fortunately, there are promising signs that additional valid cell lines are in development.
Retinoic Acid as a MYB Suppressor in ACC
Recently,
Dr. Len Zon of Harvard Medical School and Boston Children's Hospital published a
scientific article describing how retinoic acid may be an effective therapy for ACC patients with advanced disease:
https://www.ncbi.nlm.nih.gov/pubmed/30209067. For people who are not trained scientists, Boston Children's Hospital summarized the work in a
blog, providing background on how the study came to be.
An ACCRF grantee since 2011, Dr. Zon screened nearly 4,000 chemical compounds (including nearly 2,000 already-approved drugs) in zebrafish embryos to see which might reduce the activity of the MYB gene that drives most ACC tumors. Some of the most effective compounds were retinoic acids that already are widely prescribed in treating acne and a blood cancer (acute promyelocytic leukemia). ACCRF confirmed the activity of all-trans retinoic acid (ATRA) in mouse models of ACC and Dr. Zon clarified the biological mechanism by which the drug likely works.
Given the promising start in zebrafish and mice, there are efforts to initiate a clinical trial for ACC patients. Fortunately, for years many leukemia patients have taken ATRA, so doctors have a good idea of how much drug will be sufficient for therapeutic effect without significant toxicity. However, drugs that work in animal models do not always work in people. And funding for the clinical trials has not yet been secured. ACCRF will keep patients informed of the status of this and other studies that may be appropriate for ACC patients.
|
|
Needham, MA, USA, Patient Gathering
On October 21, 2018, a cheery group of 30 met outside Boston to socialize, share experiences and learn about recent research advances.
York, UK, Patient Gathering
November 18, 2018
10am to 4:30pm
|
|
Please Help Support ACC Research
|
|
|
|
|
