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Carcinoma, Intraductal, NoninfiltratingPhase 1/2NCT01023477

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

A Phase 1/2 study testing Chloroquine Standard Dose (500mg/week), Chloroquine Low Dose (250mg/week) and Breast Biopsy in people with Carcinoma, Intraductal, Noninfiltrating and DCIS, run by Inova Health Care Services at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Chloroquine Standard Dose (500mg/week), Chloroquine Low Dose (250mg/week) and Breast Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
4 sitesUnited States
Study dates
Dec 2009to Oct 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Medical Oncology and Hematology Associates of Northern Virginia

    Fairfax, Virginia, 22031

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • Virginia Surgery Associates

    Fairfax, Virginia, 22033

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

Other trials in United States

About this study

Official title: Preventing Invasive Breast Neoplasia With Chloroquine (PINC) Trial

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.

Read the 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.

Being tested
Chloroquine Standard Dose (500mg/week), Chloroquine Low Dose (250mg/week), Breast Biopsy
Keywords
Carcinoma, Intraductal, Noninfiltrating, Ductal Carcinoma In Situ, DCIS, Carcinoma, Intraductal, Breast Cancer, Breast Tumors, chloroquine, autophagy, Autophagic Cell Death, Autophagocytosis, Programmed Cell Death, Type II, Autophagy, Cellular, Autophagic Programmed Cell Death
Medical subject headings
Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Chloroquine Standard Dose (500mg/week)Drug

    Also called Aralen

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

  • Chloroquine Low Dose (250mg/week)Drug

    Also called Aralen

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

  • Breast BiopsyProcedure or surgery

    Also called Biopsy, DCIS, Ductal Carcinoma in Situ

    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.

Study groups in NCT01023477
Study groupRoleWhat they receive
Chloroquine Standard Dose (500mg/week)ExperimentalPatients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week).
Receives: Drug: Chloroquine Standard Dose (500mg/week); Procedure: Breast Biopsy
Chloroquine Low Dose (250mg/week)ExperimentalPatients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week).
Receives: Drug: Chloroquine Low Dose (250mg/week); Procedure: Breast Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Average Change in the Longest Diameter of the Breast MRI Target Lesion

    One of the primary outcomes of this study was to measure the impact of weekly chloroquine on the amount of DCIS seen on MRI.The tumor response was evaluated by RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR The longest diameter of the target lesion or primary area of non-mass enhancement was measured by digital calipers. For one patient, the longest diameter was difficult to measure due to the presence of a significant post biopsy resolving hematoma at the biopsy site. Further correlation was made based on the extent of the pre-treatment microcalcifications and post treatment areas of non-mass enhancement.

    Measured: Immediately preceding study drug treatment and again after treatment prior to surgery. The total time interval was up to 8 weeks

Secondary outcomes (3)

  1. Total Number of Treatment-Related Adverse Events

    One of the outcomes was to ensure the safety of weekly chloroquine. Patients were followed clinically during the treatment with chloroquine and during their surgery and postoperative period ( including radiation therapy). Patients were verbally assessed for additional symptoms or concerns. Patients were also examined by the provider during treatment and follow up visits to the surgeon.

    Measured: The patients were monitored from the time of diagnosis through 6 months of surgical follow up.

  2. Effect of Chloroquine on Proliferating Cell Nuclear Antigen (PCNA) Proliferation Index

    We evaluated the effect of therapy on cellular proliferation as measured by the change in proliferating cell nuclear antigen (PCNA) proliferation index. PCNA , which is elevated during the G1/S phase of the cell cycle, may be used as a marker of cellular proliferation. The PCNA proliferation index was measured as the number of PCNA positive stained cells in the DCIS lesion/ total number of cells in the lesion. The change in the PCNA index is equal to the mean PCNA proliferation index pre-treatment minus the mean PCNA proliferation index post-treatment.

    Measured: At the time of breast biopsy and again at time of surgery.

  3. Impact of Chloroquine Treatment on the Cell Signaling Kinase Levels in DCIS Lesions.

    The study evaluated the effect of chloroquine treatment on the proteomic signaling profiles of the DCIS lesions. Post treatment surgical specimens were evaluated by immunohistochemical staining to measure cell signaling kinase levels for CD68 and HMGB1. CD68 (Cluster Determinant 68) is a marker of macrophages/monocytes in the breast ducts. and HMGB1 (High Mobility Group Box 1) is involved in oxidative stress-mediated autophagy. HMGB1 is a non-histone DNA binding protein. The number of positive cells were quantified and recorded.

    .

    Measured: At the time of surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Dec 2009 (estimated)
  2. Study startDec 2009
  3. Primary completionOct 2016
  4. Study completionOct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01023477
Sponsor's protocol ID
IFHCC 09-002
Status last verified
May 2021
First submitted
1 Dec 2009
Last updated
29 Jun 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20562526

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Chloroquine Standard Dose (500mg/week), Chloroquine Low Dose (250mg/week) and Breast Biopsy in people with Carcinoma, Intraductal, Noninfiltrating and DCIS, run by Inova Health Care Services at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Average Change in the Longest Diameter of the Breast MRI Target Lesion (time frame: Immediately preceding study drug treatment and again after treatment prior to surgery. The total time interval was up to 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01023477, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021.

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