The Sharon Trial
A Clinical Trial for Metastatic Cancer With an Inherited BRCA or PALB2 Mutation Using Chemotherapy and Patients’ Own Stem Cells
Official Study Title:
SHARON: Study of Metastatic Cancers in Patients With an Inherited Defect in a Homologous Recombination Gene Using Autologous Stems Cells and Potentiated Redox Cycling to Overcome Drug Resistance to Nitrogen Mustard Derivatives
Study Sponsor:
General Oncology, Inc.
Protocol #:
GO-1
Study Phase:
1
What is the SHARON Trial for Pancreatic and Breast Cancer?
This clinical trial for Stage 4 pancreatic or breast cancer uses a novel investigational treatment designed for people with an inherited BRCA1, BRCA2, or PALB2 mutation. The treatment is designed to overcome cancer cells’ ability to evade traditional chemotherapy.
How is the treatment designed for BRCA and PALB2?
If you have a BRCA or PALB2 mutation, many of your cancer cells likely have a weakness to cancer drugs. But some of the cancer cells in you might not have that weakness and are therefore “drug-resistant.”
Killing only the weakened cells would leave resistant cells, which can multiply into a resistant tumor.
The SHARON Trial treatment is designed to kill both types of cancer cells.
The treatment includes the following study drugs: Melphalan and BCNU (cancer drugs) and Vitamins B12b and C (selected for reasons other than their vitamin properties). Infusions of your own stem cells are also given. There are 2 treatment cycles, about 6 weeks apart.
Killing Weakened Cancer Cells
Higher drug doses kill more cancer cells. However, too high a dose can cause unacceptable side effects. For this reason, standard-of-care drugs for pancreatic and breast cancer cannot be given in high enough doses to reliably eliminate even the weakened cancer cells. The problem is even greater when you have drug-resistant cancer cells. Importantly, studies show that melphalan may be able to reliably eliminate the weakened cancer cells at a dose low enough to avoid unacceptable side effects. Melphalan may also offer an advantage over PARP inhibitors: in mice with BRCA-mutated breast cancer, a single injection of melphalan had a greater anti-cancer effect than giving 28 days of the PARP inhibitor olaparib.
Killing Drug-Resistant Cancer Cells
Higher drug doses kill more cancer cells. However, too high a dose can cause unacceptable side effects. For this reason, standard-of-care drugs for pancreatic and Melphalan alone may not be enough to kill drug-resistant cancer cells. Drug resistance to melphalan can happen in several ways:
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Melphalan can be deactivated by a certain chemical inside cancer cells.
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Cancer cells can repair the damage caused by melphalan.
Melphalan needs a special transporter (which is like a doorway) to enter cells, but cancer cells can mutate and lose that doorway. The combination of BCNU, vitamin B12b, and vitamin C is designed to solve each of those problems:
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It is expected to greatly reduce the amount of the chemical that can deactivate melphalan.
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It is expected to largely shut down the cancer cell’s ability to repair itself.
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BCNU kills cancer cells just like melphalan, but it enters them without needing a transporter (similar to walking through a wall instead of needing a door).
Are any of the study drugs FDA-approved?
Not currently for pancreatic or breast cancer, but each is separately approved for other conditions. For example, melphalan has been widely used to safely and effectively treat people with blood cancers, such as myeloma, for decades. To learn more about the risks and potential benefits, you are encouraged to speak with a study doctor.
Can I enroll if I have already had other cancer treatments, such as PARP inhibitors?
Yes. You can enroll whether or not you have had prior cancer treatments, and there is no limit on the amount of prior chemotherapy.
Can I enroll if I am in remission?
Yes, you can enroll whether or not your imaging scans show any visible cancer.
How many people will be enrolling?
There is an opportunity for about 10 to 18 people to enroll.
How will my stem cells be collected?
Stem cells are present in blood and are collected in a routine procedure called apheresis.
How does this trial differ from the breast cancer trials in the 1990s that tested drugs like melphalan together with stem cells?
Those trials were not focused on people with an inherited BRCA or PALB2 mutation. In fact, recent re-analyses of those studies revealed that drugs like melphalan gave high rates of long-term survival and probable cures in those people who likely had an inherited BRCA mutation.
How does this trial differ from the well-known cancer trials that tested high-dose vitamin C?
The use of low-dose vitamin C in this trial is entirely different. Combined with the other study drugs, it has very different biochemical effects than vitamin C alone.
The Key Eligibility Criteria
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One of the following cancers:
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Stage 4 (metastatic) pancreatic cancer
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Stage 4 (metastatic) HER2-negative breast cancer
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Male or female
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A BRCA1, BRCA2, or PALB2 mutation
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This study is open to people who have already received a PARP inhibitor, as well as those who have not. There is no restriction on how many prior lines of treatment a patient has received before enrolling.
Locations
Massachusetts General Hospital, Boston, Massachusetts.
Principal investigator: Colin Weekes, M.D., Ph.D.
Memorial Sloan Kettering Cancer Center, New York, New York.
Principal investigator: Kenneth Yu, M.D.
How can I enroll or learn more about the trial?
To be put in touch with a study location of your choice, contact the study sponsor, General Oncology, by phone or e-mail:
818-4-SHARON (818.474.2766)