SHARON: A Clinical Trial for Metastatic Cancer With a BRCA or PALB2 Mutation Using Chemotherapy and Patients' Own Stem Cells

Pancreatic Cancer Clinical Trial

Official title: SHARON: Study of Metastatic Cancers in Patients With a Defect in a Homologous Recombination Gene Using Autologous Stems Cells and Potentiated Redox Cycling to Overcome Drug Resistance to Nitrogen Mustard Derivatives

Status Recruiting

Clinical Trial Summary

The clinical trial is a phase 1, single-arm trial that will evaluate the safety of the investigational treatment on metastatic cancer in patients who have a deleterious or suspected deleterious BRCA1, BRCA2, or PALB2 genetic alteration. The investigational treatment will involve 2 cycles of a combination of intravenous melphalan, BCNU, low-dose I.V. ethanol, vitamin B12b, and vitamin C in association with autologous hematopoietic stem cell infusion. A dose-escalation schedule will be employed for vitamin C.

Clinical Trial Description

In the current clinical trial, subjects with BRCA-related or PALB2-related metastatic pancreatic or breast cancer will receive a combination of melphalan, BCNU, low-dose ethanol, vitamin B12b, and vitamin C in conjunction with autologous stem cell infusion. The drug combination is designed to address multiple mechanisms of melphalan resistance. The purpose of the ethanol is the protection of RBC catalase activity.

Investigational Treatment Description:

• Hematopoietic Stem Cell Collection

1. Granulocyte colony-stimulating factor, and if needed Plerixafor, will be used to mobilize bone marrow stem cells, which will be collected by apheresis.

2. At least 2 bags of CD34+ cells, each containing at least 2 × 10^6 cells/kg, will be prepared and stored.

3. Mobilization of hematopoietic stem cells will only occur prior to the first cycle of investigational therapy.

4. If there is not a sufficient mobilization of stem cells for at least 2 cycles of chemotherapy, then no investigational drugs will be given.

• Investigational Drug Therapy and Stem Cell Infusion

1. All subjects will receive two cycles of investigational drug therapy with stem cell infusion unless precluded by adverse reactions.

2. Subjects will receive on day -2:

1. BCNU

2. Melphalan

3. Vitamin B12b

4. Vitamin C

5. Ethanol

3. On day 0, at least 2 × 10^6 CD34+ cells/kg will be infused as per the institution's standard procedures.

4. Subjects will receive supportive care as per the institution's standard procedures before, during, and after the investigational drug therapy and stem cell infusion.

• Additional Cycles a. Subjects will receive a second cycle of the investigational treatment described immediately above in "Investigational Drug Therapy and Stem Cell Infusion," with an interval of approximately 6 weeks between cycles. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Breast
• BRCA1 Mutation
• BRCA2 Mutation
• Breast Cancer Metastatic
• Breast Cancer Stage IV
• Breast Neoplasms
• Carcinoma
• HER2 Negative Breast Carcinoma
• HER2-negative Breast Cancer
• Metastatic Pancreatic Cancer
• Metastatic Pancreatic Ductal Adenocarcinoma
• Neoplasm Metastasis
• PALB2 Gene Mutation
• Pancreatic Acinar Cell Carcinoma
• Pancreatic Adenocarcinoma Metastatic
• Pancreatic Cancer
• Pancreatic Cancer Stage IV
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasms

• NCT number: NCT04150042
• Study type: Interventional
• Source: General Oncology, Inc.
• Contact: General Oncology (study sponsor)
• Phone: 818-4-SHARON (818-474-2766)
• Email: contact@SharonTrial.com
• Status: Recruiting
• Phase: Phase 1
• Start date: January 13, 2021
• Completion date: December 2025