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

Sponsor

Joaquina Baranda (Other)

Overall Status

Recruiting

CT.gov ID

NCT03560882

Collaborator

(none)

Enrollment

Location

Arm

84.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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)).

Condition or Disease	Intervention/Treatment	Phase
Malignant Disease Solid Tumor Acute Myeloid Leukemia Myelodysplastic Syndromes Cancer Relapsed Hematologic Malignancy	Drug: Atorvastatin	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 19, 2018

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in Ki-67 (protein) [baseline and up to 4 weeks]
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.
Change in caspase-3 [baseline and up to 4 weeks]
Measured by immunohistochemistry (IHC) staining. Reported as overall percent difference in the level of caspase-3 in the conformation mutant p53 samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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