Cyclosporin A for Breast Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Virginia G. Kaklamani
Must not be taking: Calcium channel blockers, antifungals, others
Disqualifiers: Renal impairment, hepatic impairment, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This will be a single arm, non-randomized, pre-surgical clinical trial of women with newly diagnosed triple negative breast cancer with high g-H2Ax (gamma H2AX antibodies) comparing changes in biomarkers from a diagnostic core needle biopsy to surgical pathology specimen or repeat core needle biopsy.
Will I have to stop taking my current medications?
Yes, you will need to stop taking certain medications, including calcium channel blockers, antifungals, and several antibiotics, among others, as they are listed in the exclusion criteria.
What evidence supports the effectiveness of the drug Cyclosporin A for treating breast cancer?
Cyclosporin A (CsA) has shown potential as an anti-tumor agent, particularly in T-cell cancers, and may enhance the effectiveness of other cancer drugs by restoring sensitivity in drug-resistant cancer cells. Although its direct impact on breast cancer is not detailed, its ability to work with other cancer treatments suggests it could be beneficial.
12345How is the drug Cyclosporin A unique in treating breast cancer?
Cyclosporin A is unique because it is primarily known as an immunosuppressive drug used to prevent organ rejection and treat autoimmune disorders, but it also shows promise in treating certain cancers, including breast cancer, by inhibiting T-lymphocyte activation and potentially restoring drug sensitivity in resistant cancer cells.
36789Eligibility Criteria
This trial is for adults with newly diagnosed triple negative breast cancer showing high levels of DNA damage. Eligible participants must be able to take oral medication, have not started treatment, and cannot be in another drug study. They should be healthy enough for surgery or biopsy after treatment and use effective contraception if childbearing potential.Inclusion Criteria
Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-hCG) pregnancy test result within 14 days prior to the first dose of CsA
Patient may not be concurrently enrolled in another investigational drug treatment study
I am 18 years old or older.
+12 more
Exclusion Criteria
Known hypersensitivity to CsA
As judged by the investigator, severe uncontrolled concurrent medical conditions, psychiatric illness, or social condition that would limit compliance with study requirements
I am currently taking certain medications.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 week
1 visit (in-person)
Treatment
Participants receive Cyclosporin A (CsA) for 14-30 days before surgery
2-4 weeks
Weekly visits and/or phone calls on Days 8, 15, and 21-30
Surgery
Participants undergo standard of care surgery (mastectomy or lumpectomy)
1 day
Follow-up
Participants are monitored for adverse events and effectiveness after surgery
2 weeks
1 visit (in-person)
Participant Groups
The trial tests Cyclosporin A's effect on biomarkers in patients with triple negative breast cancer before surgery. It's a single-arm study where all participants receive the same intervention without randomization or comparison groups.
1Treatment groups
Experimental Treatment
Group I: Cyclosporin AExperimental Treatment1 Intervention
Patients with newly diagnosed triple negative breast cancer with low or negative RAD51 (A protein coding gene that provides instructions for making a protein that is essential for repairing damaged DNA)
Cyclosporin A is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Ciclosporin for:
- Organ transplant rejection prophylaxis
- Severe active rheumatoid arthritis
- Severe plaque psoriasis
- Dry eye syndrome
🇺🇸 Approved in United States as Cyclosporine for:
- Organ transplant rejection prophylaxis
- Severe active rheumatoid arthritis
- Severe plaque psoriasis
- Dry eye syndrome
🇨🇦 Approved in Canada as Cyclosporine for:
- Organ transplant rejection prophylaxis
- Severe active rheumatoid arthritis
- Severe plaque psoriasis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mays Cancer Center, UT Health San AntonioSan Antonio, TX
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Who Is Running the Clinical Trial?
Virginia G. KaklamaniLead Sponsor
References
Bioequivalence of a new cyclosporine a formulation to Neoral. [2019]New cyclosporine A (CsA) formulations must prove their bioequivalence to Neoral, the reference CsA formulation, to allow free prescription for the patients. The aim of this study was to compare the pharmacokinetics (PK) of a new CsA formulation (Zinograf-ME), produced by Strides-Arcolab, to Neoral and to demonstrate their interchangeability in stable renal transplant recipients. Twelve-hour PK studies were obtained from 18 (13 M/5 F) adult patients (mean age 44.7 +/- 12 years). They received their renal allografts from 13 cadaver and 5 living donors. Before enrollment, all patients were receiving a third generic CsA for a mean of 48 months. Nine patients were also under azathioprine and 9 under mycophenolate mofetil; 17 received prednisone. A single oral dose of either Zinograf or Neoral was administered. The first PK study was performed with one formulation, and 1 week later, a second PK was done with the other formulation. During the washout period, patients continued taking the third CsA formulation. The drug substitution was done milligram-for-milligram. The CsA whole-blood level was measured by TDx immunoassay. Mean +/- SD of area under the curve (AUC), maximum concentration (C(max)), and concentration at the second hour (C2) of Zinograf were not statistically different from those with Neoral (4019 +/- 1466 vs 3971 +/- 1325 ng x h/mL, 998 +/- 376 vs 1021 +/- 356 ng/mL, and 707 +/- 254 vs 734 +/- 229 ng/mL, respectively). In the same way, the Zinograf 90% confidence interval for either C(max) (-123, +77 ng/mL) or AUC (-214, +311 ng.mL/h) were within the Neoral bioequivalence interval for the same parameters (+/-204 ng/mL and +/-794 ng x mL/h, respectively). These data demonstrate that the ZinografME CsA formulation is bioequivalent to Neoral.
Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring. [2019]Recently, a new oral microemulsion formulation of cyclosporin A (CsA)--Neoral (Sandoz, Basle, Switzerland)--with a higher bioavailability has become available. Ten stable paediatric renal transplant recipients with excessive variations in CsA trough levels with the original Sandimmun (Sandoz, Basle, Switzerland) preparation were switched to Neoral on a 1:1 basis. Pharmacokinetic studies revealed impaired absorption of Sandimmun in six patients. Compared with equal doses of Sandimmun, the 8-h area under the concentration-time curve increased from 1,422 to 2,657 ng x h/ml and the peak concentration rose from 319 to 824 ng/ml (P
The potential of cyclosporin A as an anti-tumour agent. [2019]Cyclosporin A (CsA) has become established as the agent of choice for the prevention of organ allograft rejection and has shown considerable promise in the clinical management of certain autoimmune disorders. The impact of CsA as an immunotherapeutic agent of major importance is attributable to its powerful, selective inhibitory action on T-lymphocyte activation and proliferation. Moreover, CsA lacks the myelotoxic and other major side effects associated with cytotoxic immunosuppressive agents, such as cyclophosphamide or azathioprine. It is now clear that CsA has a potential therapeutic role in the treatment of malignancies, especially T-cell cancers. Recent studies suggest that there may be several areas of application for CsA, either as a direct antiproliferative agent or in combination with other drugs, including inhibitors of polyamine biosynthesis or cytotoxic anti-tumour agents, including vincristine and adriamycin. In addition, CsA and non-immunosuppressive analogues have been shown to restore multi-drug sensitivity in cancer cells with acquired drug resistance. A further application of CsA may be to prevent the induction of human immune responses to therapeutic mouse monoclonal antibodies directed against tumour antigens, thereby enhancing the efficiency and safety of this form of cancer immunotherapy. Due to our incomplete understanding of the antiproliferative properties of CsA, further exploration of its potential as an anti-tumour agent must be accompanied by detailed studies aimed at elucidating its action on subcellular molecular events in both normal and malignant cells.
[Variability of the bioavailability of cyclosporine: benefit of the Neoral formulation]. [2013]After oral administration of Sandimmun, the bioavailability of cyclosporin can vary substantially especially in view of its narrow therapeutic index. As a consequence, optimal exposure of patients to the drug is sometimes difficult to ensure. The new formulation of cyclosporin, Neoral, improves the absorption of the drug. This results in an increase in bioavailability, a lower dependency on food, bile or pancreatic enzymes and a markedly reduced intra- and inter-patient variability in pharmacokinetic parameters. This allows an easier adjustment of patient exposure. The clinical efficacy of Neoral is equivalent to, or even better than, that of Sandimmun. The tolerability of the two formulations is comparable.
A possible role for cyclosporins in cancer chemotherapy. [2004]It has been established for some time that cyclosporin A (CsA) can exert cytotoxic effects in T-cell neoplasms. More recently, antiproliferative effects in a variety of non-T-cell tumour cell lines have been demonstrated. Inhibition of polyamine synthesis is a possible mechanism and combination of CsA with other polyamine inhibitors may be particularly effective. The non-immunosuppressive analogue, B3-243, is at least as effective as CsA as an antiproliferative in human lung cancer cell lines. CsA potentiates the effect of a number of cytotoxic drugs (eg adriamycin, vincristine, VP16) both in vitro and in vivo. Differential potentiation in vitro is often seen in cells with acquired drug resistance compared with their parent lines. A number of non-immunosuppressive analogues of CsA also act as 'resistance modifiers' and hence the structure/activity requirements for immunosuppression and resistance modification appear to differ.
[Comparison of the effects of 2 preparations of cyclosporin A-- Consupren and Sandimmune--from the aspect of functional and morphologic changes in rats with renal ischemia]. [2013]Cyclosporine A is in transplantology an irreplaceable immunosuppressive agent. Its only manufacturer preparation Sandimmune--was the Swiss firm Sandoz. In 1990 the Czech firm Galena introduced cyclosporine A with the name Consupren on the market. The objective of the present investigation was to assess whether the nephrotoxic effect of the two preparations is comparable, or whether it differs.
Anticancer Analysis of CD44 Targeted Cyclosporine Loaded Thiolated Chitosan Nanoformulations for Sustained Release in Triple-Negative Breast Cancer. [2023]Cyclosporine (CsA), a potent immunosuppressive chemotherapeutic medication, treats numerous cancers, particularly malignant carcinoma, acute leukemia, and triple-negative breast cancer (TNBC).
A new orthotopic model of human breast cancer in immunocompetent rats. [2016]Breast cancer is the first cause of mortality by cancer in women in North America and Western Europe. For non-estrogen-dependent tumors as well as for metastatic cancers, current therapies are of limited efficacy. Several animal models have been described but they are imperfect as they are poorly representative of what occurs in real tumors. To overcome some of these limitations, we describe a new orthotopic model of estrogen-independent breast cancer in immunocompetent rats treated with cyclosporin A (CysA).
Comparison of two formulations of cyclosporin A in the treatment of severe atopic dermatitis. Aa double-blind, single-centre, cross-over pilot study. [2017]Cyclosporin A (CsA) has been shown to be highly effective in the therapy of atopic dermatitis (AD). However, little information exists on the treatment of AD patients with Sandimmun Neoral(R) (Neoral), a microemulsion of CsA with improved pharmacokinetic properties in comparison to Sandimmun(R).