PCS6422 + Capecitabine for Breast Cancer

Recruiting at 8 trial locations

Overseen By Shanique Smythe-Peterkin, M.S.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Processa Pharmaceuticals

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

Disqualifiers: Recent cancer treatment, Cardiac disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is an adaptive Phase 2, open-label, randomized, multi-center study evaluating up to 2 regimens of PCS6422 with capecitabine (Cap) vs. standard dose of Cap alone in patients with advanced or metastatic 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 not eligible for anthracycline- or taxane-containing therapies, or other available therapies, including PD-1 or PARP inhibitors.

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.

What data supports the effectiveness of the drug PCS6422 + Capecitabine for breast cancer?

Research shows that capecitabine (Xeloda) is effective and well-tolerated in treating metastatic breast cancer, and it works well in combination with other cancer drugs. This suggests that combining capecitabine with PCS6422 could also be beneficial for breast cancer treatment. ^{1 2 3 4 5}

Is the combination of PCS6422 and Capecitabine safe for humans?

Capecitabine (also known as Xeloda) is generally well-tolerated in humans, with minimal side effects like low blood cell counts and hair loss. It has been used safely in combination with other cancer treatments for breast and colorectal cancer. ^{1 2 3 6 7}

What makes the drug PCS6422 + Capecitabine unique for breast cancer treatment?

The combination of PCS6422 with Capecitabine is unique because PCS6422 is designed to enhance the effectiveness of Capecitabine by potentially increasing its concentration in tumor cells, which may improve its cancer-fighting ability compared to using Capecitabine alone. ^{1 2 3 5 8}

Eligibility Criteria

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

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

Has a life expectancy of at least 24 weeks

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.

Trial Timeline

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

Treatment Details

Interventions

• Capecitabine (Anti-metabolites)
• PCS6422 (Anti-metabolites)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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 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]

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 (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]

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, 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 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]

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]

References

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

Future options with capecitabine (Xeloda) in (neo)adjuvant treatment of breast cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the use of capecitabine in patients with severe renal impairment (GFR [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

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

5. Germany pubmed.ncbi.nlm.nih.gov

Capecitabine bioequivalence in healthy volunteers. [2018]

6. United States 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: a phase II study. [2015]