PCS6422 + Capecitabine for Breast Cancer

Recruiting at 12 trial locations

Overseen By Sian Bigora, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Processa Pharmaceuticals

Must not be taking: Hormone therapy, 5-FU, DPD inhibitors

Disqualifiers: Recent cancer treatment, Cardiac disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination of PCS6422 (an experimental treatment) and capecitabine (also known as Xeloda, a chemotherapy drug) for individuals with advanced or metastatic breast cancer. The goal is to determine if this combination is more effective and safe compared to using capecitabine alone. It targets those unable to use other standard treatments like anthracyclines, taxanes, or other specific cancer medications. Ideal participants have breast cancer that has spread, cannot be surgically removed, and have previously found other treatments ineffective. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial requires that you stop any hormone replacement therapy at least 21 days before joining. If you've had any treatment for advanced or metastatic breast cancer, you must wait 21 days or 5 half-lives (whichever is longer) before joining. Other specific medications like IV 5-FU, oral 5-FU analogs, and DPD inhibitors must be stopped 4 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining PCS6422 with capecitabine has been tested in patients with advanced cancers. Previous studies examined different doses of capecitabine with a fixed amount of PCS6422. These studies found that adding PCS6422 to lower doses of capecitabine increased the production of cancer-fighting substances in the body.

The combination's safety is currently under study to ensure it is well-tolerated. Although specific side effects are not detailed, the treatment's advanced testing stage suggests it has demonstrated some level of safety. Treatments at this stage are generally considered reasonably safe, but ongoing studies continue to gather information on potential side effects. Participants receive close monitoring to address any health concerns promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PCS6422 combined with Capecitabine for breast cancer because it has the potential to enhance the effectiveness of Capecitabine, a standard chemotherapy drug. PCS6422 works by inhibiting an enzyme that breaks down Capecitabine, potentially allowing for lower doses of Capecitabine with fewer side effects and improved efficacy. This combination may offer a more targeted approach, which could translate to better outcomes and a more tolerable treatment experience for patients compared to traditional high-dose Capecitabine therapy.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that using PCS6422 with capecitabine (Cap) may effectively treat advanced or metastatic breast cancer. Participants in this trial will receive varying dosages of PCS6422 combined with capecitabine. One study found that 66.7% of patients experienced a period of 5 to 11 months without cancer progression. This combination has also shown early signs of effectiveness in other advanced cancers, with many patients experiencing tumor shrinkage or stability. These results suggest that PCS6422 with capecitabine might help control cancer growth in some patients. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic breast cancer who can't have treatments like anthracyclines, taxanes, PD-1 or PARP inhibitors. Participants should be able to take oral medication and have acceptable blood test results.

Inclusion Criteria

Has a life expectancy of at least 24 weeks

My breast cancer is advanced, cannot be surgically removed, and falls into one of the specified categories.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have a genetic condition that almost completely lacks DPD enzyme activity.

Is pregnant or breastfeeding

I have received 5-FU or a similar medication through IV or orally in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PCS6422 with Capecitabine or Capecitabine alone over 7 days per cycle

8 months

Weekly visits for monitoring and administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• PCS6422

Trial Overview The study compares two treatment regimens: PCS6422 combined with capecitabine versus the standard dose of capecitabine alone. It's an open-label and randomized trial, meaning both patients and researchers know which treatment is given and participants are assigned by chance.

How Is the Trial Designed?

Group I: PCS6422 40 mg + Capecitabine 450 mg or 150 mg Experimental Treatment 1 Intervention

Fixed single dose of PCS6422 administered with Capecitabine 225 mg or 75 mg BID over 7 days

Group II: PCS6422 40 mg + Capecitabine 300 mg Experimental Treatment 1 Intervention

Fixed single dose of PCS6422 administered with Capecitabine 150 mg BID over 7 days

Group III: Capecitabine 2000 mg/m2 Active Control 1 Intervention

Standard capecitabine dose at 1000 mg/m2 BID

Capecitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Processa Pharmaceuticals

Lead Sponsor

Trials

10

Recruited

380+

Published Research Related to This Trial

The oral combination therapy of capecitabine and cyclophosphamide (XC) showed an overall response rate of 35.6% in patients with metastatic breast cancer, indicating its efficacy as a treatment option.

The treatment was associated with manageable side effects, with only 11% of patients experiencing grade 3 neutropenia and mild nonhematological toxicities, suggesting that XC has an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: a phase II study. Tanaka, M., Takamatsu, Y., Anan, K., et al.[2015]

In a study of 19 colorectal cancer patients, capecitabine was shown to preferentially convert to 5-fluorouracil (5-FU) in tumor tissues, with 5-FU concentrations in tumors being 3.2 times higher than in adjacent healthy tissues, indicating effective targeting of the drug.

The enzyme thymidine phosphorylase (TP) plays a crucial role in this preferential activation, being significantly more active in colorectal tumors compared to healthy tissue, which helps explain the enhanced efficacy of capecitabine in treating colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Schüller, J., Cassidy, J., Dumont, E., et al.[2022]

A retrospective study of 12 patients with severe renal impairment (GFR <30 mL/min) showed that capecitabine can be safely administered with close monitoring and dose adjustments, despite previous contraindications from the manufacturer based on a small Phase II trial.

Most patients experienced only mild to moderate adverse effects, and some showed a positive response to treatment, indicating that capecitabine may still be effective in this population when managed carefully.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR Jhaveri, KD., Flombaum, C., Shah, M., et al.[2022]

Capecitabine, an oral medication, showed at least equivalent efficacy to intravenous 5-FU plus leucovorin in treating metastatic colorectal cancer, with an overall response rate of 18.9% compared to 15.0% for 5-FU/LV among 602 patients.

Capecitabine had a more favorable safety profile, resulting in significantly lower rates of stomatitis and neutropenia, while being associated with a higher incidence of hand-foot syndrome, making it a convenient and effective alternative to traditional IV treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. Van Cutsem, E., Twelves, C., Cassidy, J., et al.[2022]

In a study of 42 patients with advanced breast and colorectal cancer, capecitabine showed a partial response rate of 29.16% for breast cancer and 11.76% for colorectal cancer, indicating its potential efficacy in these pretreated patients.

Capecitabine was well tolerated with low toxicity levels, as most adverse reactions were mild, although 7.14% of patients experienced grade 3 hand-foot syndrome, and hypertriglyceridemia was noted in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. Stathopoulos, GP., Koutantos, J., Lazaki, H., et al.[2022]

Capecitabine is a well-tolerated treatment for metastatic breast cancer, showing minimal side effects like myelosuppression and hair loss, which makes it a promising option for combination therapies with other anticancer drugs.

Ongoing phase II/III trials are investigating the use of capecitabine in early breast cancer treatment, and preliminary results indicate that it may provide significant benefits when used as part of adjuvant and neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. Fumoleau, P., Cameron, D.[2019]

A study evaluating the bioequivalence of two capecitabine formulations found that the new formulation by Eurofarma Laboratórios Ltda. is bioequivalent to the established Xeloda® formulation, with plasma concentration ratios within the FDA's acceptable range.

The capecitabine formulations were well tolerated by healthy male subjects, indicating that the new formulation is safe for use and suitable for further clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine bioequivalence in healthy volunteers. Machado Matos, M., Bosio-Guimarães, RA., Schmidt Niederauer, AJ., et al.[2018]

Capecitabine (Xeloda) is an effective treatment for advanced/metastatic breast cancer, showing a response rate of 20% in a phase 2 trial with a median survival time of 452 days for patients who were resistant to previous therapies.

The most common side effects reported were hand-foot syndrome and various blood-related issues, indicating that while Capecitabine can be beneficial, it also carries a risk of significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological and clinical properties of Xeloda (Capecitabine), a new oral active derivative of fluoropyrimidine. Nishida, M.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06568692

A Phase 2 Study of PCS6422 With Capecitabine in ... The goal of the study is to assess the efficacy and safety of PCS6422 + Cap as a treatment option for patients with advanced or metastatic breast cancer who are ...

2. processapharmaceuticals.com processapharmaceuticals.com/news-media/press-releases/detail/122/processa-pharmaceuticals-announces-positive-efficacy

Press Releases Eight of 12 evaluable patients (66.7%) had progression-free survival (PFS) ranging from 5 to 11 months. At the highest NGC-Cap dose, ...

3. onclive.com onclive.com/view/ngc-cap-demonstrates-preliminary-efficacy-in-stage-iii-iv-gi-cancer

NGC-Cap Demonstrates Preliminary Efficacy in Stage III/IV ... NGC-Cap demonstrated preliminary efficacy in stage III/IV gastrointestinal cancer, with 66.7% of patients showing partial response or stable ...

4. withpower.com withpower.com/trial/phase-2-triple-negative-breast-neoplasms-7-2024-4ce73

PCS6422 + Capecitabine for Breast Cancer The goal of the study is to assess the efficacy and safety of PCS6422 + Cap as a treatment option for patients with advanced or metastatic breast cancer who are ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/processa-breast-cancer-trial/

Processa doses first subject in Phase II breast cancer trial Processa Pharmaceuticals has dosed the first subject in its Phase II clinical trial of NGC-Cap to treat patients with breast cancer.

6. processapharmaceuticals.com processapharmaceuticals.com/news-media/press-releases/detail/128/processa-pharmaceuticals-announces-first-patient-dosed-in

Press Releases The five-year survival rate for those diagnosed with metastatic breast cancer is approximately 30%. About Capecitabine Administered with PCS6422 ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT04861987

A Study of the Safety and PK of PCS6422 (Eniluracil) ... The NGC-Cap Phase 1b study evaluated ascending doses of capecitabine when combined with a fixed dose of PCS6422 in patients with advanced, relapsed or ...

8. bioanalysis-zone.com bioanalysis-zone.com/processa-pharmaceuticals-releases-data-update-on-their-novel-therapeutic-strategy-for-better-cancer-management/

Processa Pharmaceuticals releases data update on their ... This study has already demonstrated that the addition of PCS6422 to low doses of capecitabine results in the formation of more cancer-killing ...