Study of the Efficacy of Chloroquine in the Treatment of Ductal Carcinoma in Situ (The PINC Trial)

NCT ID: NCT01023477

Last Updated: 2021-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2016-10-31

Brief Summary

The purpose of this study is to test the hypothesis that chloroquine will reduce the ability of ductal carcinoma in situ (DCIS) to survive and spread. Participants will receive either chloroquine standard dose (500mg/week) or chloroquine low dose (250mg/week) for 1 month prior to surgical removal of the tumor.

Detailed Description

The purpose of this study is to test the hypothesis that inhibiting the autophagy pathway in DCIS will reduce the capacity of DCIS to survive and invade. The study will examine the safety and effectiveness of neoadjuvant chloroquine administration for a one month period to patients with low, intermediate grade, or high grade DCIS. We will evaluate whether this treatment will reduce the capacity of DCIS neoplastic cells, existing within the duct, to survive, induce lesion regression, and kill the invasive DCIS progenitor cells.

Conditions

Carcinoma, Intraductal, Noninfiltrating; DCIS; Ductal Carcinoma In Situ

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chloroquine Standard Dose (500mg/week)

Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week).

Group Type: EXPERIMENTAL

Chloroquine Standard Dose (500mg/week)

Intervention Type: DRUG

Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.

Breast Biopsy

Intervention Type: PROCEDURE

Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery.

Chloroquine Low Dose (250mg/week)

Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week).

Group Type: EXPERIMENTAL

Chloroquine Low Dose (250mg/week)

Intervention Type: DRUG

Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.

Breast Biopsy

Intervention Type: PROCEDURE

Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery.

Interventions

Chloroquine Standard Dose (500mg/week)

Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.

Intervention Type: DRUG

Chloroquine Low Dose (250mg/week)

Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.

Intervention Type: DRUG

Breast Biopsy

Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery.

Intervention Type: PROCEDURE

Other Intervention Names

Aralen; Aralen; Biopsy; DCIS; Ductal Carcinoma in Situ

Eligibility Criteria

Inclusion Criteria

• Patients must have a tissue diagnosis of low, intermediate or high grade ductal carcinoma in situ or ductal carcinoma in situ with microinvasion.
• Patients with ductal carcinoma in situ undergoing either lumpectomy/radiation or mastectomy.
• Patients must be female at least 18 years of age.
• Patients must have a signed tissue acquisition consent and have at minimum, adequate samples of primary fresh tissue or blood available for use in this study.
• No history of a previous invasive cancer in the last five years with the exception of minimally invasive non-melanoma skin cancer.
• Normal liver function based on Liver Function Tests (Total Bilirubin and Asparate transaminase (AST) <1.5 X Upper Limit of Normal).
• Normal White Blood Count (WBC) (3.5-10.8 x 103µL), Platelet count (PLT) (140-400 x 103µL), and Hematocrit (HCT)(37-52%)
• Potassium within the normal range of 3.5-5.3 mEq/L
• Adequate renal sufficiency (serum creatinine <1.5 mg/dL).
• Eastern Cooperative Oncology Group performance status 0-2.
• Are able to swallow and retain oral medication.
• No underlying ocular/retinal pathology.
• No medically documented preexisting auditory damage.
• Subjects should be willing to abstain from use of hormonal therapies (e.g. hormone replacement therapy, oral contraceptive pills, hormone-containing Intra Uterine Device (IUD)s, and E-string) and chronic non-steroidal anti-inflammatory (NSAID) s for the duration of the study (chronic use of NSAID's is defined as a frequency >3 times/week for more than two weeks per year and includes low dose aspirin).
• Subjects with child-bearing potential must agree to use adequate contraception (total abstinence (no sexual intercourse), use of condom with spermicide or sterilization surgery, including tubal ligation (tubes tied) or hysterectomy (removal of the uterus or womb)) prior to study entry and for the duration of study treatment phase. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

If a subject is of child-bearing potential (women are considered not of child-bearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have a documented negative serum or urine pregnancy test before starting treatment.

Exclusion Criteria

• Patients with a prior history of chemotherapy, hormonal ablation therapy and/or radiation therapy.
• History of other invasive cancer in the previous 5 years other than minimally invasive non-melanoma skin cancer.
• Patient desires not to participate in the study.
• Inability to consent.
• Current or recent pregnancy (within 12 months),
• Current use of hormone-containing forms of birth control such as implants (i.e. Norplants, or injectables ( i.e. depo-provera)
• Currently lactating.
• Patients with history of renal or hepatic insufficiency.
• Current diagnosis for depression, including treatment with an Selective Serotonin Reuptake Inhibitor (SSRI).
• History of prior treatment with chloroquine for malaria within past 24 months.
• History of allergic reactions to quinolones or chloroquine.
• Active diagnosis of psoriasis or currently receiving treatment for psoriasis.
• History of porphyria.
• History of known Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency.
• Alcoholism or hepatic disease.
• History of epilepsy or seizures in the past 20 years.
• History of deep vein thrombosis or pulmonary embolism.
• History of human immunodeficiency virus (HIV) disease and/or treatment with anti-HIV agents.
• Receiving concurrent treatment with prohibited medications (refer to Table 1 for details on prohibited medications); Examples include: ampicillin, antacids, cimetidine, cyclosporine, kaolin, magnesium trisilicate, coumarin-type anticoagulants, macrolide antibiotics (e.g., clarithromycin, isoniazid, and erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants (e.g. fluoxetine and fluvoxamine), calcium channel blockers (e.g. verapamil and diltiazem), steroids and their modulators (e.g., gestodene, raloxifene, and mifepristone), and several herbal and dietary components (e.g. bergamottin and glabridin).
• Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

George Mason University

OTHER

Sponsor Role: collaborator

University of Pittsburgh Medical Center

OTHER

Sponsor Role: collaborator

United States Department of Defense

FED

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: collaborator

Inova Health Care Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kirsten H Edmiston, MD, FACS

Role: PRINCIPAL_INVESTIGATOR

Inova Fairfax Hospital Cancer Center

Priscilla McAuliffe, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Magee-Women's Hospital of UPMC

Locations

Medical Oncology and Hematology Associates of Northern Virginia

Fairfax, Virginia, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Virginia Surgery Associates

Fairfax, Virginia, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Countries

United States

References

Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, Migneco G, Witkiewicz AK, Martinez-Cantarin MP, Flomenberg N, Howell A, Pestell RG, Lisanti MP, Sotgia F. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle. 2010 Jun 15;9(12):2423-33. doi: 10.4161/cc.9.12.12048. Epub 2010 Jun 15.

Reference Type: DERIVED

PMID: 20562526 (View on PubMed)

Other Identifiers

IFHCC 09-002

Identifier Type: -

Identifier Source: org_study_id