CFI-402257 + Fulvestrant for Solid Tumors

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

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 1 study of investigational agent CFI-402257 in patients with advanced cancer. The purpose of this study is to see how safe and tolerable CFI-402257 is in cancer patients as well as the pharmacokinetics (PK). This study is the first time that CFI-402257 is given to humans.

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.

What data supports the effectiveness of the drug CFI-402257 + Fulvestrant for solid tumors?

Research shows that Fulvestrant is effective in treating hormone-sensitive breast cancer, especially when combined with other targeted agents, improving outcomes like progression-free survival. While specific data on CFI-402257 is not provided, the combination approach with Fulvestrant has shown promise in similar contexts. ^{1 2 3 4 5}

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

The research articles provide safety information about Fulvestrant, which is generally well-tolerated in treating advanced breast cancer, but adding other agents can increase side effects. However, there is no specific safety data available for the combination of CFI-402257 and Fulvestrant. ^{1 2 3 6 7}

What makes the drug CFI-402257 unique for treating solid tumors?

CFI-402257 is unique because it is being studied in combination with fulvestrant, a hormone therapy, to target solid tumors, potentially offering a novel approach by combining a new investigational drug with an existing treatment to enhance effectiveness. ^{8 9 10 11 12}

Research Team

Philippe Bedard

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

A comparison of fulvestrant plus a targeted agent with fulvestrant alone in hormone receptor-positive advanced breast cancer that progressed on prior endocrine therapy: a meta-analysis. [2020]

3. United States 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. [2022]

4. Turkey pubmed.ncbi.nlm.nih.gov

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study. [2023]

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

Current and future perspectives on fulvestrant. [2019]

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

TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor-Positive Breast Cancer. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer. [2018]

8. Italy pubmed.ncbi.nlm.nih.gov

Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

A phase Ib dose allocation study of oral administration of lucitanib given in combination with fulvestrant in patients with estrogen receptor-positive and FGFR1-amplified or non-amplified metastatic breast cancer. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

A phase I study of sunitinib combined with modified FOLFOX6 in patients with advanced solid tumors. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]

12. Germany 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. [2021]