CFI-402257 + Paclitaxel for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, CFI-402257, combined with the standard chemotherapy drug paclitaxel, to determine if it slows breast cancer growth more effectively than paclitaxel alone. The trial targets women with advanced or recurring breast cancer that cannot be surgically removed and for whom no cure exists. Ideal candidates have previously received treatment for breast cancer, require further systemic therapy, and can take oral medications. Participants should not have HER2-positive breast cancer or active infections. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to early-stage cancer treatment advancements.

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.

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

Previous studies have shown that the combination of CFI-402257 and paclitaxel is generally safe for patients with HER2-negative breast cancer. Research indicates that most people tolerate this treatment well, with usually manageable side effects. Although some side effects were reported, they were not severe for most participants. This suggests that the treatment is relatively safe, though some risks remain. As with any new treatment, weighing both the potential benefits and side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CFI-402257 combined with Paclitaxel for breast cancer because it introduces a novel approach by using an oral drug, CFI-402257, which targets specific cancer cell mechanisms. Unlike traditional treatments that mainly rely on chemotherapy, this combination promises a more targeted attack on cancer cells, potentially reducing side effects and improving effectiveness. Additionally, the intermittent dosing schedule of CFI-402257 might offer patients a more manageable treatment experience compared to continuous regimens.

What evidence suggests that CFI-402257 combined with paclitaxel could be an effective treatment for breast cancer?

Research shows that CFI-402257, a new drug for breast cancer, can slow tumor growth in lab tests. In this trial, participants will receive a combination of CFI-402257 and the common chemotherapy drug paclitaxel. Early studies indicate that 11-14% of patients with advanced HER2-negative breast cancer responded to this combination treatment, suggesting it might work for some individuals. The combination is also considered safe for most patients, as it doesn't cause severe side effects. Overall, while early data remains limited, there is hope that this treatment could offer more benefits than using paclitaxel alone. ^{1 2 4 5 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03568422

Study Details | NCT03568422 | CFI-402257 in ... CFI-402257 is a new type of drug for breast cancer. Laboratory tests show that it may help slow the growth of breast cancer.

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)00062-4/fulltext

38MO IND.236: A Canadian Cancer Trial Group (CCTG ... A Canadian Cancer Trial Group (CCTG) phase Ib trial of combined CFI-402257 and weekly paclitaxel (Px) in patients with HER2-negative (HER2-) advanced breast ...

3. researchgate.net researchgate.net/publication/339911211_19O_A_phase_Ib_trial_of_CFI-402257_in_combination_with_weekly_paclitaxel_in_patients_with_advanced_HER2-negative_HER2-_breast_cancer_aBC

19O A phase Ib trial of CFI-402257 in combination with ... Interim reports from these studies indicate some evidence of efficacy; however, overall reported response rates are not high (about 11-14%).

4. bioworld.com bioworld.com/articles/682501-cfi-402257-plus-paclitaxel-shows-manageable-safety-in-her2-negative-breast-cancer-patients

CFI-402257 plus paclitaxel shows manageable safety in ... CFI-402257 plus paclitaxel shows manageable safety in HER2-negative breast cancer patients · Good efficacy and safety profile reported for Sch- ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9371652/

CFI-402257, a TTK inhibitor, effectively suppresses ... Targeting SAC proteins might result in high level of genomic instability and poly/aneuploidy to an extent even cancer cells could not tolerate ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/22/NCT03568422/Prot_SAP_000.pdf

2021-AUG-03 CCTG TRIAL: IND.236 These preclinical results indicate that CFI-402257, as monotherapy, may have clinical activity in patients with breast cancer. Paclitaxel, a chemotherapeutic ...