Cyclosporin A for Breast Cancer

Overseen By Epp Goodwin

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Virginia G. Kaklamani

Must not be taking: Calcium channel blockers, antifungals, others

Disqualifiers: Renal impairment, hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 2-4 weeks

24 Participants Needed

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. ^{1 2 3 4 5}

How 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. ^{3 6 7 8 9}

Research Team

Virginia G. Kaklamani

Principal Investigator

The University of Texas Health Science Center at San Antonio

Eligibility 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

My breast cancer is early stage, not driven by estrogen, progesterone, or HER2.

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.

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)

Treatment Details

Interventions

• Cyclosporin A

Trial Overview 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.

Participant Groups

Group I: Cyclosporin A Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Virginia G. Kaklamani

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

A study involving 18 stable renal transplant recipients demonstrated that the new cyclosporine A formulation, Zinograf-ME, has pharmacokinetic properties that are bioequivalent to the reference formulation, Neoral.

Key pharmacokinetic measures, including the area under the curve (AUC) and maximum concentration (Cmax), showed no statistically significant differences between Zinograf-ME and Neoral, confirming that they can be used interchangeably in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of a new cyclosporine a formulation to Neoral. David-Neto, E., Kakehashi, E., Alves, CF., et al.[2019]

A new oral microemulsion formulation of cyclosporin A (Neoral) shows significantly improved absorption compared to the original Sandimmun formulation, with the area under the concentration-time curve increasing from 1,422 to 2,657 ng x h/ml and peak concentration rising from 319 to 824 ng/ml (P < 0.01).

In pediatric renal transplant recipients who previously experienced malabsorption with Sandimmun, switching to Neoral on a 1:1 basis initially caused a decrease in creatinine clearance, but this was reversible with a dose reduction of 9%-25%, stabilizing creatinine clearance to pre-conversion levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring. Bökenkamp, A., Offner, G., Hoyer, PF., et al.[2019]

Cyclosporin A (CsA) is effective in preventing organ rejection and shows promise in treating autoimmune disorders due to its selective inhibition of T-lymphocyte activation, with fewer side effects compared to traditional cytotoxic drugs.

Recent studies indicate that CsA may also be beneficial in treating T-cell cancers, either alone or in combination with other therapies, and can help restore drug sensitivity in resistant cancer cells, highlighting its potential as an anti-tumor agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of cyclosporin A as an anti-tumour agent. McLachlan, G., Smart, LM., Wallace, HM., et al.[2019]

The new formulation of cyclosporin, Neoral, significantly improves drug absorption and bioavailability compared to the older Sandimmun formulation, leading to more consistent patient exposure.

Neoral shows equivalent or superior clinical efficacy to Sandimmun while maintaining similar tolerability, making it a more reliable option for patients requiring cyclosporin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Variability of the bioavailability of cyclosporine: benefit of the Neoral formulation]. Humbert, H.[2013]

Cyclosporin A (CsA) has shown cytotoxic effects not only in T-cell neoplasms but also in various non-T-cell tumor cell lines, potentially through the inhibition of polyamine synthesis.

The non-immunosuppressive analogue B3-243 is as effective as CsA in reducing the proliferation of human lung cancer cells, and CsA can enhance the effectiveness of certain cytotoxic drugs, especially in drug-resistant cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A possible role for cyclosporins in cancer chemotherapy. Twentyman, PR.[2004]

In a study involving 65 rats, both Sandimmune (Sandoz) and Consupren (Galena) showed comparable nephrotoxic effects when administered after kidney damage, indicating similar safety profiles for these cyclosporine A preparations.

After 21 days, the only notable difference was a higher serum creatinine level in the Consupren group, which may be linked to higher cyclosporine levels, but overall nephrotoxicity remained similar between the two drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[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]. Bohdanecká, M., Chadimová, M., Schück, O., et al.[2013]

A new polymeric nanoformulation (NF) of Cyclosporine, designed with hyaluronic acid for targeted delivery, showed improved drug encapsulation (85%) and sustained release for up to 72 hours, enhancing its effectiveness against triple-negative breast cancer (TNBC).

In vitro tests indicated that this nanoformulation significantly inhibited tumor cell growth more effectively than raw Cyclosporine, suggesting that the targeted delivery system could lead to better therapeutic outcomes in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer Analysis of CD44 Targeted Cyclosporine Loaded Thiolated Chitosan Nanoformulations for Sustained Release in Triple-Negative Breast Cancer. Abduh, MS.[2023]

A new orthotopic model of estrogen-independent breast cancer in immunocompetent rats was developed, which allows for better representation of human tumor behavior compared to existing models.

Using this model, tumors grew more rapidly when human breast cancer cells were injected directly into the mammary fat pad, making it a promising tool for studying breast cancer and testing new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new orthotopic model of human breast cancer in immunocompetent rats. Akla, B., Monteil, J., Paraf, F., et al.[2016]

In a pilot study involving 14 patients with atopic dermatitis, Neoral (a microemulsion of cyclosporin A) showed significantly greater improvement in disease activity and extent of disease compared to Sandimmun after just 2 weeks of treatment.

Both Neoral and Sandimmun were found to be effective and well tolerated over 8 weeks, but Neoral's faster onset of action suggests it could be a preferable option for initial treatment of severe atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two formulations of cyclosporin A in the treatment of severe atopic dermatitis. Aa double-blind, single-centre, cross-over pilot study. Zurbriggen, B., Wüthrich, B., Cachelin, AB., et al.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of a new cyclosporine a formulation to Neoral. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring. [2019]

3. England pubmed.ncbi.nlm.nih.gov

The potential of cyclosporin A as an anti-tumour agent. [2019]

4. France pubmed.ncbi.nlm.nih.gov

[Variability of the bioavailability of cyclosporine: benefit of the Neoral formulation]. [2013]

5. Greece pubmed.ncbi.nlm.nih.gov

A possible role for cyclosporins in cancer chemotherapy. [2004]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

[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]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Anticancer Analysis of CD44 Targeted Cyclosporine Loaded Thiolated Chitosan Nanoformulations for Sustained Release in Triple-Negative Breast Cancer. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

A new orthotopic model of human breast cancer in immunocompetent rats. [2016]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of two formulations of cyclosporin A in the treatment of severe atopic dermatitis. Aa double-blind, single-centre, cross-over pilot study. [2017]