Phase 2A Pilot C3 Trial of Recurrent/Refractory Metastatic Advanced Pancreatic Cancer

NCT06030622 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 1727019-4
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this trial are: 1) To evaluate the safety and tolerability of C3 administration with Gemcitabine; and 2) To assess the disease response following C3 administration with Gemcitabine. The main question it aims to answer are: 1) Is C3 in combination with Gemcitabine safe, tolerable, and effective for reducing improving advanced stage pancreatic cancer? and 2) Can C3 in combination with Gemcitabine prolong the lives of patients with advanced stage pancreatic cancer. Participants will receive a combination of metformin (850 mg twice a day), digoxin (0.25 mg once a day), and simvastatin (20 mg once a day), also known as C3, and Gemcitabine (as per standard of care) for 2 years. If patients decline Gemcitabine, they will be offered the C3 medications only.

Conditions

Pancreatic Cancer Metastatic

Keywords

C3 trial; metformin; simvastatin; digoxin; pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Primary Outcome: Safety and tolerability

  Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0

  28 days

Secondary Outcomes (1)

• Secondary Outcome: Biomarkers

  Before and 2 months after C3 treatment

Study Arms (2)

Gemcitabine and C3 (Combination Digoxin, Simvastatin, and Metformin)

EXPERIMENTAL

Study participants will be offered metformin (850 mg twice a day), digoxin (0.25 mg once a day), and simvastatin (20 mg once a day) combination (C3) and Gemcitabine.

Drug: Gemcitabine and C3 (Metformin, Simvastatin, and Digoxin)

C3 (Combination Digoxin, Simvastatin, and Metformin) only

EXPERIMENTAL

Study participants will be offered C3 only metformin (850 mg twice a day), digoxin (0.25 mg once a day), and simvastatin (20 mg once a day) combination (C3) if they decline Gemcitabine.

Drug: C3 (Metformin, Simvastatin, and Digoxin) only

Interventions

Gemcitabine and C3 (Metformin, Simvastatin, and Digoxin) DRUG

Combination treatment of Metformin, Simvastatin and Digoxin with Gemcitabine (Arm 1)

Also known as: Glucophage, Zocor, Digitalis, Gemzar

Gemcitabine and C3 (Combination Digoxin, Simvastatin, and Metformin)

C3 (Metformin, Simvastatin, and Digoxin) only DRUG

C3 only (Metformin, Simvastatin, and Digoxin) if patients decline Gemcitabine (Arm 2).

Also known as: Glucophage, Zocor, Digitalis

C3 (Combination Digoxin, Simvastatin, and Metformin) only

Eligibility Criteria

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

You may qualify if:

• Subject ≥18 years with histologically confirmed pancreatic cancer.
• Refractory, intolerant to, or with disease progression after at least one standard of care regimen.
• ECOG performance status (PS) 0-1.
• Pretreatment biopsy and/or adequate archival tissue available for BIRC5 protein level evaluation.
• Adequate organ and marrow function: absolute granulocyte count ≥1,000/mm3, platelets ≥100,000/mm3, total bilirubin ≤ institutional upper normal limit, AST/ALT ≤2x institutional upper limit of normal, and creatinine \<1.5 mg/dL or calculated creatinine clearance \> 60ml / min (Cockcroft-Gault Equation).
• Subject has recovered to CTCAE Grade 1 (except for alopecia) or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.
• If participant of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry. Serum pregnancy tests will be conducted at the time of screening, when other blood draws are obtained (See Appendix III: Time-Table of Procedures).
• Ability to understand and the willingness to sign a written informed protocol specific consent.
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• No known active infections at the time of enrollment as determined by negative procalcitonin level.

You may not qualify if:

• Anti-cancer chemotherapy, biologic therapy or immunotherapy within 3 weeks or radiation therapy within 2 weeks of first investigational product administration.
• Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
• Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
• Known history of rhabdomyolysis.
• History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the Investigator.
• Known chronic Hepatitis B or C infection.
• Have current active infection requiring systemic antibiotic treatment.
• History of severe allergic, anaphylactic, hypersensitivity reactions or previous intolerance to Metformin, Simvastatin, and/or Digoxin.
• Patients with significant cardiac disease or condition listed below (unless clearance obtained by cardiology):
• Wolff-Parkinson-White Syndrome.
• Previous MI within last 6 months of C1D1.
• Evidence of residual electrographic pattern consistent with heart block., for example atrio-ventricular (AV) heart block (currently ongoing).
• History of ventricular fibrillation.
• Sick Sinus Syndrome or Sinus bradycardia thought to be caused by sinus node disease, unless effectively treated.
• Heart failure with preserved LVEF, including constructive pericarditis, and amyloid heart disease.

Sponsors & Collaborators

• State University of New York - Downstate Medical Center: lead

Study Sites (1)

SUNY Downstate Health Sciences University

Brooklyn, New York, 11203, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Metformin; Simvastatin; Digoxin; Single Person

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Biguanides; Guanidines; Amidines; Organic Chemicals; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates; Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors

Study Officials

• Mohan Preet, MD

  SUNY Downstate Health Sciences University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seema Chittalae, MD

CONTACT

(718) 221-6594; seema.chittalae@downstate.edu

Moro Salifu, MD

CONTACT

(718) 270-1584; moro.salifu@downstate.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncologist

Model Details: The treatment plan is as follows: The first 3 patients enrolled in the study, will receive metformin (850 mg twice a day), digoxin (0.25 mg once a day), and simvastatin (20 mg once a day) for 28 days. If no toxic effects, the remaining 22 patients will be enrolled. Patients will be provided C3 medications every 28 days and will continue on the C3 medication for at least 2 years, or until death or recurrence/advancement of the disease. If more than one patient develops a toxic event, the dose will be reduced to metformin 850 mg/day, simvastatin 5 mg/day, and digoxin 0.0625 mg/day. If no further toxicities, then the remaining patients will receive the lower dose. If however, more than two patients develop a toxic event, then study discontinuation will be considered. If patients decline first line therapy (Gemcitabine), they will be offered the choice of C3 medications only.

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 11, 2023
• Study Start: April 17, 2024
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: September 30, 2024 to September 30, 2026
• Access Criteria: Data will be made available to the general public only through presentations and publications with no identifiers. Data will be shared in continuing education programs at a national and international level. Data will be shared in appropriate forums. All Protected Health Information (PHI) will be restricted to the PI and their research designees. Researchers who seek to obtain data will submit a request to the PI and IRB for approval. However, no PHI will be shared. The PI will ensure that shared data are protected. Data to be transferred for additional analyses will be de-identified and an agreement for confidentiality of data will be obtained from the secondary user who must agree to protect the data. This will include communicating the data protection plan; determining whether the original consent agreement limited the use of the data in future studies; and obtaining a written and binding agreement from the recipient that the data are bound by all of the agreed conditions.

Locations

US (1)