Clinical trial NCT03560882: A Pilot Trial of Atorvastatin in Tumor Protein 53 (p53) -Mutant and p53 Wild-Type Malignancies
Official title: A Pilot Trial of Atorvastatin in p53-Mutant and p53 Wild-Type Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Malignant Disease
Solid Tumor
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Cancer
Relapsed Hematologic Malignancy
Keywords: atorvastatin
p53
tumor resection
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2018-06-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)).


Eligibility criteria: 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

Primary outcomes:
measure: Change in conformational mutant tumor protein 53 (p53)
timeFrame: baseline and up to 4 weeks
Secondary outcomes:
measure: Change in Ki-67 (protein)
timeFrame: baseline and up to 4 weeks
measure: Change in caspase-3
timeFrame: baseline and up to 4 weeks
Other outcomes:
Locations:
city: Fairway
country: United States
facility: University of Kansas Cancer Center - CRC
state: Kansas
Study officials:
affiliation: The University of Kansas Cancer Center
name: Joaquina Baranda, MD
role: PRINCIPAL_INVESTIGATOR
References: