SHARON: A Clinical Trial for Metastatic Cancer Using Chemotherapy and Patients' Own Stem Cells

NCT04150042 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: GO-1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The clinical trial is a phase 1, single-arm trial that will evaluate the safety of the investigational treatment on metastatic pancreatic cancer and metastatic breast cancer. The investigational treatment will involve 2 cycles of a combination of intravenous melphalan, BCNU, vitamin B12b, and vitamin C with autologous hematopoietic stem cell infusion. A dose-escalation schedule is being employed for the vitamin C.

Conditions

Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Cancer; Breast Cancer Metastatic; Pancreatic Cancer Stage IV; Adenocarcinoma of the Breast; Pancreatic Adenocarcinoma Metastatic; BRCA1 Mutation; BRCA2 Mutation; Pancreatic Acinar Cell Carcinoma; Pancreatic Cancer; Metastatic Pancreatic Ductal Adenocarcinoma; Breast Cancer Stage IV; HER2-negative Breast Cancer; HER2 Negative Breast Carcinoma; PALB2 Gene Mutation; Pancreas Cancer, Metastatic; Pancreas Cancer, Recurrent; Pancreas Cancer; Stage IV Pancreatic Cancer; Stage 4 Pancreatic Cancer

Keywords

pancreatic adenocarcinoma; pancreatic cancer; BRCA; BRCA1; BRCA2; melphalan; BCNU; carmustine; vitamin C; vitamin B12b; autologous stem cell infusion; stage 4 pancreatic cancer; metastatic pancreatic cancer; pancreatic acinar cell carcinoma; pancreatic ductal adenocarcinoma; PDAC; breast cancer; stage 4 breast cancer; stage IV pancreatic cancer; stage IV breast cancer; stem cells; HER2-negative breast cancer; PALB2; metastatic breast cancer; BRCA pancreatic cancer; BRCA breast cancer

Outcome Measures

Primary Outcomes (14)

• Rate of Sinusoidal obstruction syndrome

  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).

  30 days after treatment

• Rate of Idiopathic or Non-Infective Pulmonary Toxicity ≥ Grade 3

  The American Thoracic Society Committee on Idiopathic Pneumonia Syndrome definition will be employed.

  3 months after the last treatment

• Rate of Idiopathic or Non-Infective Pulmonary Toxicity ≥ Grade 3

  The American Thoracic Society Committee on Idiopathic Pneumonia Syndrome definition will be employed.

  6 months after the last treatment

• Rate of Presumptive Oxalate Nephropathy

  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).

  Within 48 hours of vitamin C treatment

• Rate of Cytokine Release Syndrome ≥ Grade 3

  Cytokine release syndrome will be assessed by the criteria of CTCAE Version 5.0. Elevation of plasma cytokine levels consistent with the diagnosis of cytokine release syndrome must be present.

  Within 48 hours of each vitamin C treatment

• Rate of Mucositis ≥ Grade 3

  Mucositis will be assessed using the WHO Mucositis Scale. Grading is from 0 (no symptoms) to 4 (no possible alimentation).

  Day 7 after each treatment

• Rate of Mucositis ≥ Grade 3

  Mucositis will be assessed using the WHO Mucositis Scale. Grading is from 0 (no symptoms) to 4 (no possible alimentation).

  Day 14 after each treatment

• Rate of Mucositis ≥ Grade 3

  Mucositis will be assessed using the WHO Mucositis Scale. Grading is from 0 (no symptoms) to 4 (no possible alimentation).

  Day 21 after each treatment

• Rate of Delayed Engraftment of Neutrophils

  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.

  Day 21 after each treatment

• Rate of Failed Engraftment of Neutrophils

  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.

  Day 30 after each treatment

• Rate of Delayed Engraftment of Platelets

  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.

  Day 30 after each treatment

• Overall incidence rate of adverse events

  Adverse event is defined any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related.

  Until 12 months after the second stem cell treatment

• Overall incidence rate of serious adverse events

  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. * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. * A congenital anomaly or birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

  Until 12 months after the second stem cell treatment

• Overall incidence rate of Grade 3-5 adverse events

  Grading will be measured using Common Terminology Criteria for Adverse Events version 5.0

  Until 12 months after the second stem cell treatment

Secondary Outcomes (14)

• Objective response according to RECIST version 1.1

  1 month after the first stem cell treatment

• Objective response according to RECIST version 1.1

  1 month after the second stem cell treatment

• Objective response according to RECIST version 1.1

  3 months after the second stem cell treatment

• Objective response according to RECIST version 1.1

  6 months after the second stem cell treatment

• Objective response according to RECIST version 1.1

  9 months after the second stem cell treatment

Study Arms (1)

Chemotherapy/stem cell treatment

EXPERIMENTAL

Drug: Melphalan; Drug: BCNU; Drug: Vitamin B12B; Drug: Vitamin C; Device: Autologous Hematopoietic Stem Cells

Interventions

Melphalan DRUG

Intravenous melphalan (to be given in conjunction with the other listed drugs).

Chemotherapy/stem cell treatment

BCNU DRUG

Intravenous BCNU (to be given in conjunction with the other listed drugs).

Also known as: Carmustine

Chemotherapy/stem cell treatment

Vitamin B12B DRUG

Intravenous vitamin B12b (to be given in conjunction with the other listed drugs).

Also known as: Hydroxocobalamin

Chemotherapy/stem cell treatment

Vitamin C DRUG

Intravenous vitamin C (to be given in conjunction with the other listed drugs).

Also known as: Ascorbic acid, sodium ascorbate

Chemotherapy/stem cell treatment

Autologous Hematopoietic Stem Cells DEVICE

After each cycle of chemotherapy, participants will receive an autologous hematopoietic stem cell infusion.

Chemotherapy/stem cell treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Pancreatic or breast cancer, as described below.
• Stage IV (based on AJCC staging guidelines) at the time of enrollment.
• a. Note that potential subjects with stage IV cancer that have had a complete response from prior chemotherapy are still potentially eligible.
• Expected survival time ≥ 6 months, as determined by the investigator.
• Life expectancy not severely limited by diseases other than malignancy, as determined by the investigator.
• Karnofsky score ≥ 60%.
• No chemotherapy within 2 weeks of enrollment.
• Prior surgical resection or ablation of the primary tumor is allowed but not required.
• If post-surgical, the subject must be at least 28 days post-op with the surgical wounds healed and significant complications resolved.
• Potential subjects who have received previous chemotherapy and/or PARP inhibitors may be enrolled.
• Measurable or non-measurable disease by the revised response evaluation criteria in solid tumors (RECIST) v.1.1.
• For potential subjects with a germline BRCA1, BRCA2, or PALB2 mutation:
• a. The mutation must be known to be deleterious or suspected to cause functional impairment as assessed by a CLIA-certified laboratory according to the variant classification criteria described in the study protocol.
• For potential subjects with somatic BRCA1, BRCA2, or PALB2 mutations:

You may not qualify if:

• Rapid disease progression or clinical features concerning for onset of rapid symptomatic deterioration, as determined by the investigator.
• Biliary tract obstruction.
• Current cholangitis. A biliary stent in situ does not otherwise exclude protocol participation.
• A history of only one episode of cholangitis and fewer than 30 days have passed since discontinuation of antibiotic treatment.
• A history of multiple episodes of cholangitis and after discussion between the site study team and sponsor medical monitor and careful evaluation for suitability the patient is deemed to be unsuitable for the trial due to risk of recurring cholangitis.
• Portal hypertension.
• Sinistral portal hypertension.
• Obliteration or significant obstruction of the major veins or arteries (e.g., portal vein, superior mesenteric artery, superior mesenteric vein).
• Clinically significant malignant ascites or malignant pleural effusion, as determined by the investigator.
• Metastatic lesion to the heart or eye.
• Chemotherapy for an indication other than treatment of the current cancer within the past 1 year with a more than 30% risk of recurrence as determined by the investigator.
• Known or suspected metastatic involvement of the central nervous system.
• Left ventricular ejection fraction less than 45% by Multigated Acquisition Scan or echocardiogram (or significantly below the lower limit of normal for the specific test).
• Clinically significant structural heart disease or vascular disease.
• Myocardial infarction within 6 months prior to enrollment; New York Heart Association (NYHA) Class III or IV heart failure; angina; uncontrolled ventricular arrhythmias; or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

Sponsors & Collaborators

• General Oncology, Inc.: lead
• Myriad Genetics, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

COMPLETED

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Recurrence

Interventions

Melphalan; Carmustine; Vitamin B 12; Hydroxocobalamin; Ascorbic Acid

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Arnold Glazier, M.D.

  General Oncology, Inc.

  STUDY DIRECTOR

Central Study Contacts

General Oncology (study sponsor)

CONTACT

818-4-SHARON (818-474-2766); contact@SharonTrial.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: November 4, 2019
• Study Start: January 13, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 29, 2026

Record last verified: 2026-01

Locations

US (2)