Immunotherapy with CFI-400945 for Breast Cancer

Not currently recruiting at 5 trial locations

Overseen By Lesley Seymour

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Growth factors, Full dose warfarin

Disqualifiers: Other malignancies, Infections, Cardiac, 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: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called CFI-400945, an immunotherapy, for certain types of breast cancer. The goal is to determine if this drug can help when standard treatments like chemotherapy have been tried but the cancer remains advanced or spreading. The study includes three groups: one with triple-negative breast cancer, one with specific genetic changes (PTEN-null), and another with different genetic markers. Women who have undergone at least one chemotherapy treatment and have specific types of breast cancer may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot receive other anti-cancer treatments while on the trial. Additionally, certain drugs listed in Appendix V Table 1 are not allowed, and you should avoid certain fruits like grapefruit due to potential interactions with the study drug.

Is there any evidence suggesting that CFI-400945 is likely to be safe for humans?

Research has shown that CFI-400945 is generally well-tolerated. One study found it safe at doses up to 64 mg, although some patients experienced neutropenia, a drop in white blood cells. Monitoring blood cell levels during treatment is important. The drug has demonstrated a good safety record in other studies as well, though some side effects, such as issues with cell division, have been noted. Overall, CFI-400945 appears to be a promising option with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Unlike the standard treatments for breast cancer, which typically include chemotherapy, hormone therapy, and targeted therapies, CFI-400945 works by targeting a unique cellular process. This investigational drug inhibits a protein called Polo-like kinase 4 (PLK4), which is crucial for cell division and tumor growth. Researchers are excited because this mechanism could potentially halt cancer cells more effectively, offering hope for patients with specific types of breast cancer, like triple-negative and hormone receptor-positive subtypes. By focusing on this novel target, CFI-400945 may provide a new avenue for treating cancers that are resistant to conventional therapies.

What evidence suggests that CFI-400945 could be an effective treatment for breast cancer?

Research has shown that CFI-400945, a new cancer treatment, can potentially reduce tumor size. This drug targets Polo-Like Kinase 4 (PLK4), a protein involved in cell division. In studies, CFI-400945 slowed cancer cell growth and even caused cancer cells to die. Tests in animals and some patients indicated that it was well tolerated with few side effects. Notably, it demonstrated strong anti-tumor effects in models with PTEN deficiency, a common trait in some breast cancers. In this trial, participants will be divided into different cohorts based on their breast cancer subtype to evaluate the effectiveness of CFI-400945 in each group. ^{1 3 6 7 8}

Who Is on the Research Team?

David Cescon

Principal Investigator

Princess Margaret Cancer Centre, Toronto, ON

Rossanna Pezo

Principal Investigator

Sunnybrook Health Sciences Centre, Toronto, ON

Are You a Good Fit for This Trial?

This trial is for female patients over 18 with advanced/metastatic breast cancer who've had chemotherapy including anthracycline and taxane. They must be able to swallow pills, have no serious illnesses that could interfere with the study, and not be pregnant or breastfeeding. Participants need a life expectancy of at least 3 months, adequate organ function, and must agree to use contraception.

Inclusion Criteria

Patients must be willing to use a Pillsy medication event monitoring system

I have given permission for my tissue sample to be used for research.

Patients must have a life expectancy of 3 months or longer

Exclusion Criteria

I do not have any serious illnesses or infections that would prevent me from following the study's requirements.

I have had cancer before, but it was either skin cancer treated fully, cervical cancer treated without spreading, or any cancer treated over 2 years ago with no current signs of disease.

I have not used growth factors in the last 28 days and won't need them during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CFI-400945 to assess its effects on advanced/metastatic breast cancer

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• CFI-400945

Trial Overview The trial tests CFI-400945 in women who have already undergone chemotherapy for breast cancer. It aims to see if this oral medication can further slow disease progression compared to standard treatments. Patients will use a Pillsy system for monitoring pill intake.

How Is the Trial Designed?

Group I: Cohort 3: Not PTEN-null, ER+ and/or PR+, HER2- Experimental Treatment 1 Intervention

N=9 to 24 patients

Group II: Cohort 2: PTEN-null, ER+ and/or PR+, HER2- Experimental Treatment 1 Intervention

N=9 to 24 patients

Group III: Cohort 1: TNBC Experimental Treatment 1 Intervention

N=9 to 24 patients

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Stand Up To Cancer Canada-Canadian Cancer Society Breast Cancer Dream Team

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

Breast cancer immunotherapy, particularly therapeutic vaccines, is being explored as a potential treatment option due to the severe side effects associated with conventional therapies, but no breast cancer vaccine has yet been approved for clinical use.

Current breast cancer vaccine strategies, including protein/peptide, dendritic cell, and genetic vaccines, often fail to provide clinical benefits on their own and are typically used in combination with other treatments like chemotherapy or radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence. Abbaspour, M., Akbari, V.[2022]

The combination of the FRα vaccine TPIV200 and the PD-L1 inhibitor durvalumab was well tolerated in 27 patients with advanced platinum-resistant ovarian cancer, showing a low grade 3 toxicity rate of 18.5%.

While the overall response rate was low (3.7% partial response and 33.3% stable disease), the median overall survival was notably long at 21 months, suggesting potential benefits from this immunotherapy approach in a heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial. Zamarin, D., Walderich, S., Holland, A., et al.[2021]

Advancements in gene transfer technology have opened new avenues for developing immunotherapy for breast cancer, focusing on the transfer of genes that enhance immune function and target tumor antigens.

Immunotherapy is expected to be most effective when used alongside traditional treatments, particularly in targeting micrometastatic disease to lower the chances of cancer returning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for carcinoma of the breast: Genetic immunotherapy. Strong, TV.[2019]

The combination of ConvitVax, an autologous tumor cell vaccine, with anti-PD-1 therapy showed improved antitumor effects in a breast cancer model, evidenced by increased tumor necrosis and enhanced immune cell infiltration.

This study suggests that combining ConvitVax with checkpoint inhibitors like anti-PD-1 could lead to more effective and personalized breast cancer treatments, especially considering the vaccine's low cost and ease of preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a ConvitVax/anti-PD-1 combined immunotherapy for breast cancer treatment. Godoy-Calderón, MJ., González-Marcano, E., Carballo, J., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03624543

CFI-400945 in Patients With Advanced/Metastatic Breast ... This drug has been shown to shrink tumours in animals and has been studied in some patients and appears well tolerated with little side effects. CFI-400945 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33866248/

Anticancer effects of radiation therapy combined with Polo ... Here we show that a novel inhibitor of Polo-Like Kinase 4 (PLK4), CFI-400945, in combination with radiation, exhibits a synergistic anti-cancer effect in TNBC ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04176848

CFI-400945 and Durvalumab in Patients With Advanced ... CFI-400945 may slow down the growth of cancer cells or may cause cancer cells to die. This drug has been shown to shrink tumours in animals and has been studied ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12268609/

Investigation of effects of CFI-400945 and ionizing ... CFI-400945 is a novel orally administered drug (16) that dysregulates centriole duplication and causes mitotic defects that exacerbate genomic ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1535610814002219

Functional Characterization of CFI-400945, a Polo-like ... CFI-400945 was shown to have significant antitumor activity as a single agent in a variety of preclinical tumor models, including those with PTEN deficiency.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31303643/

Safety and tolerability of CFI-400945, a first-in-class ... - PubMed Conclusions: CFI-400945 is well tolerated at 64 mg with dose-dependent neutropenia. Favourable pharmacokinetic profiles were achieved with ...

7. selleckchem.com selleckchem.com/products/cfi-400945.html

CFI-400945 | PLK inhibitor | Mechanism | Concentration CFI-400945 is well tolerated in breast cancer xenograft models, in particular those deficient in the tumor suppressor PTEN. Upon intermittent oral dosing, in a ...

8. dcchemicals.com dcchemicals.com/coa/COA_DC70301.html

CFI-400945 fumarate|1616420-30-4|COA CFI-400945 is a potent, highly selective, orally available PLK4 inhibitor with Ki of 0.26 nM and IC50 of 2.8 nM, does not significantly inhibits PLK1/2/3 at ...