A Pilot Trial of Atorvastatin in Tumor Protein 53 (p53) -Mutant and p53 Wild-Type Malignancies

A Pilot Trial of Atorvastatin in p53-Mutant and p53 Wild-Type Malignancies

This is a window-of-opportunity trial to determine if atorvastatin given for 1 to 4 weeks at a dose of 80 milligrams per day (mg/day) is sufficient to decrease the level of conformational mutant tumor protein 53 (p53) in malignant diseases (solid tumor and relapsed Acute Myeloid Leukemia (AML)).

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Cancer; Solid Tumor; Malignant Disease; Relapsed Hematologic Malignancy
• Intervention / Treatment: Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Cancer Center - CRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability of participant to understand this study, and participant to sign a written informed consent. Legally authorized representative is not allowed to sign consent for participant.
• Participants with tumor protein 53 (TP53) immunohistochemistry (IHC)-positive tumors
• Participants whose screening IHC shows TP53-IHC-negative including wild type (WT) and null.
• Participants with histologic or cytologic confirmation of any malignant disease who are planning and eligible to undergo surgical resection. For participants with Solid Tumors Only
• Participants with previously treated acute myeloid leukemia (AML) are eligible if they relapse and are in between two treatment regimens
• No concurrent or recent (within 30 days) use of systemic therapy including chemotherapy, immunotherapy, hormonal therapy, cancer vaccine, or local therapy for the cancer.
• Formalin-fixed paraffin-embedded (FFPE) tumor tissue deemed adequate for IHC analysis and next generation sequencing (NGS) are required. Bone marrow aspirate tissue samples from participants with AML are required.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate organ and marrow function
• A negative urine or serum pregnancy test within 7 days before Day 1 dose of study medication, if female participant is of childbearing potential.
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use two forms of adequate contraception (hormonal AND barrier method of birth control) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

• Current or anticipated use of other investigational agents while participating in this study.
• Pregnant or breast feeding.
• Diagnosis of squamous cell cancer of the oropharynx
• Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast), unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
• Prior use of statins in the past 30 days.
• History of rhabdomyolysis
• Active liver disease
• Participants who currently consume substantial quantities of alcohol (Male, more than 4 drinks a day, Female, more than 2 drinks a day)
• Concurrent use of drugs associated with myopathy
• Hypersensitivity to atorvastatin or any component of the formulation
• Untreated hypothyroidism
• Inability to comply with study and follow-up procedures as judged by the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin; Atorvastatin 80 milligrams (mg) per day, orally for 1 - 4 weeks before surgery (surgery not part of clinical trial)	Drug: Atorvastatin; Atorvastatin tablet, 80mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in conformational mutant tumor protein 53 (p53)	Measured by immunohistochemistry (IHC) staining. Reported as overall percent difference in the level of conformation mutant p53.	baseline and up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ki-67 (protein)	Measured by immunohistochemistry (IHC) staining. Reported as overall percent difference in the level of Ki-67 (also known as MKI67) in the conformation mutant p53 samples.	baseline and up to 4 weeks
Change in caspase-3	Measured by immunohistochemistry (IHC) staining. Reported as overall percent difference in the level of caspase-3 in the conformation mutant p53 samples.	baseline and up to 4 weeks

Collaborators and Investigators

• Sponsor: Joaquina Baranda
• Investigators: Principal Investigator: Joaquina Baranda, MD, The University of Kansas Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2018
• Primary Completion (Actual): October 14, 2022
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: p53; atorvastatin; tumor resection
• Additional Relevant MeSH Terms: Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Neoplasms; Myelodysplastic Syndromes; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IIT-2018-p53Atorva

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No