CFI-402257 + Paclitaxel for Breast Cancer

Recruiting at 3 trial locations

Overseen By Pierre-Olivier Gaudreau

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Warfarin, Investigational drugs

Disqualifiers: HER2 positive, Cardiovascular conditions, 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: Unknown

37 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications, but there is a requirement for a 'washout period' (time without taking certain medications) for some treatments. It's best to discuss your specific medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug CFI-402257 + Paclitaxel for breast cancer?

Research shows that nab-paclitaxel (a form of paclitaxel) is effective in treating breast cancer, with higher response rates and better safety compared to traditional paclitaxel. It is approved for use in breast cancer after other treatments have failed, suggesting its potential effectiveness in combination with other drugs like CFI-402257. ^{1 2 3 4 5}

Is the combination of CFI-402257 and Paclitaxel safe for humans?

The safety of nab-paclitaxel (Abraxane), a form of paclitaxel, has been studied and it generally shows a better safety profile with fewer severe side effects compared to traditional paclitaxel. It is approved for use in breast cancer treatment and has been shown to have less toxicity, such as a lower rate of severe neutropenia (a condition where there is a low count of a type of white blood cell), compared to solvent-based paclitaxel. ^{1 2 3 6 7}

What makes the drug CFI-402257 + Paclitaxel unique for breast cancer treatment?

The drug CFI-402257 + Paclitaxel is unique because it uses a novel formulation of paclitaxel called nanoparticle albumin-bound paclitaxel (Abraxane), which does not require toxic solvents, leading to safer administration and potentially higher drug concentration in tumors, improving efficacy and reducing side effects compared to traditional paclitaxel formulations. ^{1 3 6 8 9}

What is the purpose of this trial?

This trial tests a new drug, CFI-402257, combined with an existing chemotherapy drug, paclitaxel, in breast cancer patients. It aims to find the highest safe dose of CFI-402257 and evaluate if this combination works better than using paclitaxel by itself.

Research Team

Philippe Bedard

Principal Investigator

Princess Margaret Cancer Centre, Toronto, ON

Mihaela Mates

Principal Investigator

Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON

Eligibility Criteria

This trial is for adult women with advanced or metastatic HER2-negative breast cancer who have not responded well to non-taxane chemotherapy. They must be in good physical condition (ECOG 0 or 1), able to swallow pills, and willing to use effective contraception. Exclusions include previous taxane treatment in the metastatic setting, certain heart conditions, uncontrolled illnesses, known drug hypersensitivity, and recent major surgery.

Inclusion Criteria

You have a documented disease that has been confirmed by clinical or radiological tests. The tests must have been done within the last 21 days (or 28 days if the results were negative). For phase Ib, you don't need to have specific measurements, but for phase II, your disease needs to meet specific size criteria on different tests.

You have already received other treatments like hormone therapy, immunotherapy, or targeted therapies.

You have enough white blood cells called neutrophils in your body.

Exclusion Criteria

You have breast cancer that is positive for the HER2 protein.

Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol.

You have had heart problems that have not been treated or are not under control. Even if your heart condition is managed, your heart's pumping ability should be at least 50%.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive CFI-402257 with paclitaxel to determine the maximum tolerated dose

4 weeks

Weekly visits for dose escalation monitoring

Phase II Treatment

Participants receive CFI-402257 with paclitaxel at the determined safe dose to evaluate its effect on breast cancer

2 years

Monthly visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CFI-402257
• Paclitaxel

Trial Overview The study tests CFI-402257 combined with paclitaxel against breast cancer. CFI-402257 is a new drug that has shown promise in early studies and animal models by potentially slowing tumor growth. The trial will compare its effectiveness when added to the standard chemotherapy drug paclitaxel.

Participant Groups

Group I: CFI-402257 + Paclitaxel Experimental Treatment 2 Interventions

Oral CFI-402257 on intermittent schedule:\* days 1, 2, 8, 9, 15 \& 16 q4w Plus Paclitaxel 80 mg/m2 IV days 1, 8 \& 15 every 28 days

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Canadian Breast Cancer Foundation

Collaborator

Trials

26

Recruited

8,300+

Ontario Institute for Cancer Research

Collaborator

Trials

24

Recruited

9,200+

Findings from Research

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

Nab-paclitaxel, a novel formulation of paclitaxel, has shown higher response rates and a better safety profile compared to conventional paclitaxel in a phase III clinical trial, making it a promising option for breast cancer treatment.

This formulation allows for higher doses to be administered over shorter infusion times without the need for special equipment or pre-medications, and it is now approved for use in patients with metastatic breast cancer after prior chemotherapy failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer. Vishnu, P., Roy, V.[2021]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

In a study involving 74 patients with metastatic melanoma, nab-Paclitaxel showed a response rate of 21.6% in chemotherapy-naive patients and 2.7% in previously treated patients, indicating better efficacy in those who had not undergone prior treatment.

The treatment was well tolerated, with 78% of previously treated patients and 49% of chemotherapy-naive patients able to complete therapy without dose reductions, suggesting a favorable safety profile compared to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Hersh, EM., O'Day, SJ., Ribas, A., et al.[2020]

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

In a study involving 17 patients with malignant solid tumors, nab-paclitaxel (Abraxane) showed a significantly higher exposure to unbound paclitaxel compared to solvent-based paclitaxel, which may enhance its effectiveness against tumors.

The pharmacokinetics of nab-paclitaxel remained consistent across treatment cycles, indicating stable drug behavior and suggesting improved tolerability and efficacy due to its unique formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Gardner, ER., Dahut, WL., Scripture, CD., et al.[2022]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

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

Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. [2018]

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

A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer]. [2018]

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

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]