CFI-402257 + Fulvestrant for Solid Tumors

Not currently recruiting at 2 trial locations

Overseen By Philippe Bedard, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must be taking: Aromatase inhibitors, CDK4/6 inhibitors

Must not be taking: Warfarin, Pimozide, Cyclosporine, others

Disqualifiers: Pregnancy, Infections, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment, CFI-402257, for individuals with advanced cancer to determine its safety and how the body processes it. Participants will take CFI-402257 capsules either alone or with an additional medication, Fulvestrant, commonly used for certain types of breast cancer. The trial seeks individuals with advanced cancer, including specific cases of breast cancer, who have not had success with other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including full dose warfarin and specific drugs like Alfentanil, Pimozide, and others listed in the exclusion criteria. If you are on these medications, you may need to stop them to participate in the trial.

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

Research has shown that CFI-402257, when used alone, is generally safe. Patients typically tolerated the treatment well and experienced few serious side effects. In studies, patients took CFI-402257 orally, which helped slow tumor growth.

Currently, research is ongoing for the combination of CFI-402257 with Fulvestrant. Fulvestrant is already a known treatment for certain cancers and is generally well-tolerated. The researchers aim to determine if combining these two treatments can be safe and effective for patients with advanced cancer.

Since this is the first time CFI-402257 is being tested in humans, information is limited. However, earlier findings suggest it has been manageable for patients. The ongoing trial will provide more insights into its safety when used with Fulvestrant. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CFI-402257 because it targets solid tumors in a novel way. Unlike traditional chemotherapy, which attacks fast-growing cells indiscriminately, CFI-402257 specifically inhibits a protein involved in cell division, potentially leading to fewer side effects. In Cohort C, the combination of CFI-402257 with Fulvestrant, a hormone therapy, might enhance its effectiveness against hormone-receptor-positive tumors by tackling the cancer on multiple fronts. This dual approach could offer a more powerful and targeted treatment option compared to existing therapies.

What evidence suggests that CFI-402257 might be an effective treatment for advanced cancer?

Research has shown that CFI-402257 is a promising treatment for solid tumors. It blocks TTK, a protein that aids cancer cell growth and division. Studies on mice demonstrated that CFI-402257 can significantly slow colon cancer growth. Early human studies indicate that it is generally safe and shows signs of efficacy. In this trial, some participants will receive CFI-402257 alone, while others will receive it in combination with Fulvestrant. When combined with Fulvestrant, CFI-402257 has shown early signs of high effectiveness in treating hormone receptor-positive breast cancer. Overall, these findings suggest that CFI-402257, either alone or with Fulvestrant, might effectively combat certain cancers. ^{1 4 6 7 8}

Who Is on the Research Team?

Philippe Bedard

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or breast cancer, where standard treatments no longer work. Participants need to have measurable disease, be in relatively good health (ECOG 0-1), and able to take oral meds. They should expect to live more than 3 months and agree to use effective birth control.

Inclusion Criteria

I am fully active or can carry out light work.

Cohort C: Must have a life expectancy of greater than 3 months

Cohort A: Must have measurable disease as per RECIST v 1.1 guidelines

Exclusion Criteria

I have symptoms of heart failure.

I have ongoing chest pain or had a recent heart attack.

I have a long-term irregular heartbeat or a prolonged QT interval.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Different dose levels of CFI-402257 were tested to find the maximum tolerated dose (MTD)

Not specified

Dose Expansion

Further assessment of safety, tolerability, and pharmacokinetics of the MTD in additional patients

Not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CFI-402257

Trial Overview The study tests CFI-402257's safety, tolerability, and how the body processes it. It's a phase 1 trial which means this drug is being given to humans for the first time. Patients will also receive Fulvestrant, an existing cancer treatment.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment 2 Interventions

CFI-402257 capsules will be taken orally, once a day, every day + Fulvestrant injection on day 1 and day 15 of every 28 day cycle

Group II: Cohort B Experimental Treatment 1 Intervention

CFI-402257 capsules will be taken orally, once a day, every day.

Group III: Cohort A Experimental Treatment 1 Intervention

CFI-402257 capsules will be taken orally, once a day, every day.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Fulvestrant is an effective estrogen antagonist for postmenopausal women with hormone-sensitive advanced breast cancer, particularly after they have progressed on other antiestrogen therapies, and it has recently been approved at a higher dose of 500 mg/month based on clinical trial results.

While fulvestrant alone is effective, combining it with growth factor signaling inhibitors may enhance its efficacy, and further research is needed to understand resistance mechanisms in patients who still respond to antiestrogen therapy after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer. Oakman, C., Moretti, E., Santarpia, L., et al.[2018]

Targeted and immunological therapies have significantly improved survival rates in patients with solid tumors, demonstrating the effectiveness of treatments that focus on specific genetic and immunological changes in tumors.

Current clinical trials are exploring the optimal timing and sequencing of these therapies, which include various approved agents for cancers like prostate, breast, lung, and melanoma, indicating a shift towards more personalized cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. Grünwald, V., Rickmann, M.[2021]

In a study involving 451 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in terms of time to progression, with median times of 5.5 months for fulvestrant and 5.1 months for anastrozole.

Both treatments were well tolerated, with low withdrawal rates due to adverse events (3.2% for fulvestrant and 1.3% for anastrozole), indicating that fulvestrant is a safe and effective option for patients who have progressed on prior endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. Howell, A., Robertson, JF., Quaresma Albano, J., et al.[2022]

In a study of 400 postmenopausal women with advanced breast cancer, fulvestrant was found to be as effective as anastrozole in delaying disease progression, with a median time to progression of 5.4 months for fulvestrant compared to 3.4 months for anastrozole.

Fulvestrant also demonstrated a significantly longer duration of response in patients who responded to treatment, with a median duration of 19.0 months compared to 10.8 months for anastrozole, indicating it may provide a more sustained benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. Osborne, CK., Pippen, J., Jones, SE., et al.[2022]

The maximum tolerated dose (MTD) of OSI-461 was determined to be 1,000 mg taken orally twice daily in combination with mitoxantrone, with the combination generally well tolerated by patients with advanced solid tumors.

Out of the patients studied, 10% experienced a partial response and 50% had stable disease, indicating that while the combination was safe, the response rates were similar to those seen with mitoxantrone alone, leading to the decision not to pursue further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone. Resta, LP., Pili, R., Eisenberger, MA., et al.[2021]

In a study of 256 patients with metastatic hormone-positive breast cancer, fulvestrant treatment resulted in a median overall survival of 29.7 months, indicating its effectiveness in a real-life setting.

Patients who received fulvestrant before chemotherapy experienced significantly better outcomes compared to those who used it after chemotherapy, highlighting the importance of treatment sequencing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study. Güven, DC., Yıldırım, HÇ., Erul, E., et al.[2023]

A study involving 134 patients with metastatic estrogen receptor-positive breast cancer identified a novel gene signature that can predict response to fulvestrant treatment, highlighting potential new therapeutic targets.

Increased expression of the gene TFAP2C was linked to a decreased response to fulvestrant, suggesting it could serve as a predictive biomarker for treatment outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor-Positive Breast Cancer. Jeselsohn, R., Barry, WT., Migliaccio, I., et al.[2018]

In a review of 61 patients with pancreatic adenocarcinoma treated with FOLFIRINOX, the regimen demonstrated clinical effectiveness with a median overall survival of 13.5 months, despite significant adverse events and dose modifications in over half of the treatment cycles.

The most common severe side effect was neutropenia, affecting 19.7% of patients, but there were no therapy-related deaths, indicating that while FOLFIRINOX can cause serious side effects, it remains a viable treatment option for both metastatic and locally advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. Peddi, PF., Lubner, S., McWilliams, R., et al.[2022]

In a phase I study involving 53 patients with advanced solid tumors, the combination of sunitinib and modified FOLFOX6 (mFOLFOX6) was found to be tolerable, with maximum tolerated doses (MTDs) identified as 50 mg/day for a 2-week on/2-week off schedule and 25 mg/day for continuous daily dosing.

The study reported dose-limiting toxicities such as neutropenia and thrombocytopenia, but also showed preliminary antitumor effects, with partial responses observed in some patients, indicating potential efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of sunitinib combined with modified FOLFOX6 in patients with advanced solid tumors. Leong, S., Eckhardt, SG., Chan, E., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05251714

CFI-402257, a Potent and Selective TTK Inhibitor, in Solid ... The purpose of this study is to test the safety of an investigational drug called CFI-402257 alone in advanced solid tumors and in combination with Fulvestrant ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO2-04-13/743562/Abstract-PO2-04-13-TWT-203-PHASE-1b-2-STUDY-OF-CFI

TWT-203: PHASE 1b/2 STUDY OF CFI-402257 AS ... A first-in-human phase 1 study of CFI-402257 (NCT02792465) demonstrated a tolerable safety profile when enrolled as a monotherapy in solid ...

3. pnas.org pnas.org/doi/10.1073/pnas.1700234114

Functional characterization of CFI-402257, a potent and ... CFI-402257 was well-tolerated at the doses examined as measured by little to no decrease in body weight (<10% change) and normal behavior. Together, these ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT376176

Phase 1b/2 dose-confirming study of CFI-402257 as a ... A first-in-human phase 1 study of CFI-402257 administered orally as a single agent, demonstrated a tolerable safety profile and evidence of clinical activity ...

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

CFI-402257, a TTK inhibitor, effectively suppresses ... CFI-402257 remarkably suppressed the growth of HCT116-derived colon cancer in immune deficient mice (16). Toxicology study showed that CFI- ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS1123

TWT-203: Phase 1b/2 dose-confirming study of CFI ... A first-in-human phase 1 study of CFI-402257 administered orally as a single agent, demonstrated a tolerable safety profile and evidence of clinical activity

7. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/P6-10-13/718061/Abstract-P6-10-13-An-update-to-a-Phase-I-trial-of

Abstract P6-10-13: An update to a Phase I trial of CFI-402257 ... CFI-402257 is a potent and highly selective inhibitor of TTK. Robust suppression of tumor growth was achieved upon oral dosing of single agent CFI-402257.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04559

CFI-402257, a Potent and Selective TTK Inhibitor, in Solid ... The purpose of this study is to test the safety of an investigational drug called CFI-402257 alone in advanced solid tumors and in combination with Fulvestrant ...