SHARON: A Clinical Trial for Metastatic Cancer With a BRCA or PALB2 Mutation Using Chemotherapy and Patients' Own Stem Cells
- Conditions
- Interventions
- Registration Number
- NCT04150042
- Lead Sponsor
- General Oncology, Inc.
- Brief 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,...
- Detailed 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 o...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Chemotherapy/stem cell treatment Vitamin B12B - Chemotherapy/stem cell treatment Ethanol - Chemotherapy/stem cell treatment Melphalan - Chemotherapy/stem cell treatment BCNU - Chemotherapy/stem cell treatment Vitamin C - Chemotherapy/stem cell treatment Autologous Hematopoietic Stem Cells -
- Primary Outcome Measures
Name Time Method Overall incidence rate of adverse events Until 12 months after the second stem cell treatment Adverse event is defined any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related.
Overall incidence rate of serious adverse events Until 12 months after the second stem cell treatment An adverse event is considered serious if, in the view of either the investigator or Sponsor, it results in any of the following outcomes:
* Death.
* A life-threatening adverse event.
* Inpatient hospitalization or prolongation of existing hospitalization.
...Rate of Sinusoidal obstruction syndrome 30 days after treatment Sinusoidal obstruction syndrome diagnosis and grading will use the European Society for Blood and Marrow Transplantation's Revised Diagnosis and Severity Criteria for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Adult Patients as published in 2016. Gradings are from mild to very severe (multi-organ dysfunction/multi-organ failure).
Overall incidence rate of Grade 3-5 adverse events Until 12 months after the second stem cell treatment Grading will be measured using Common Terminology Criteria for Adverse Events version 5.0
Rate of Presumptive Oxalate Nephropathy Within 48 hours of vitamin C treatment Oxalate nephropathy will be presumed if there is acute kidney injury or increased creatinine, grade 3 or higher by the criteria of CTCAE Version 5.0 within 48 h of the administration of vitamin C, in the absence of a clear alternative explanation (an example of an alternative explanation is tumor lysis syndrome).
Rate of Delayed Engraftment of Neutrophils Day 21 after each treatment Neutrophil engraftment is defined as an absolute neutrophil count ≥ 500/microliter for 3 days, with the date of engraftment being the first of those 3 days. Delayed engraftment is engraftment that occurs after 21 days but within 30 days.
Rate of Idiopathic or Non-Infective Pulmonary Toxicity 6 months after the last treatment The American Thoracic Society Committee on Idiopathic Pneumonia Syndrome definition will be employed.
Rate of Mucositis ≥ Grade 3 Day 21 after each treatment Mucositis will be assessed using the WHO Mucositis Scale. Grading is from 0 (no symptoms) to 4 (no possible alimentation).
Rate of Failed Engraftment of Neutrophils Day 30 after each treatment Neutrophil engraftment is defined as an absolute neutrophil count ≥ 500/microliter for 3 days, with the date of engraftment being the first of those 3 days. Failure to engraft within 30 days will be considered an engraftment failure.
Rate of Delayed Engraftment of Platelets Day 30 after each treatment Platelet engraftment is defined as a platelet count ≥ 20,000/microliter for 3 days, with the date of engraftment being the first of those 3 days. Delayed engraftment is engraftment that occurs after 30 days.
- Secondary Outcome Measures
Name Time Method Overall Survival Until 12 months after the second stem cell treatment Overall survival will be measured from the time of enrollment until death from any cause and will be measured in the intent-to-treat population. Subjects without a known date of death will be censored on the date the subject was last known to be alive.
Progression-Free Survival Until 12 months after the second stem cell treatment Progression-free survival will be measured as time-to-progression with the starting time being the time of enrollment.
A subject is also considered to have progressed if one of the following occurs:
* Progression as determined by a RECIST evaluation.
* Unequivocal evidence of clinical progression.
...Objective response according to RECIST version 1.1 12 months after the second stem cell treatment Objective response will be evaluated according to RECIST version 1.1 as assessed by the independent core imaging facility. This endpoint will be evaluated with CT scans with contrast of the abdomen, pelvis, and chest and other sites as clinically indicated at each time point.
Objective response rate in metastatic lesions 12 months after the second stem cell treatment Objective response of metastatic lesions will be evaluated according to RECIST version 1.1 as assessed by the independent core imaging facility, but excluding the primary tumor from the analysis. This endpoint will be evaluated with CT scans with contrast of the abdomen, pelvis, and chest and other sites as clinically indicated at each time point.
Trial Locations
- Locations (2)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States