CFI-402257 + Fulvestrant for Breast Cancer

Recruiting at 3 trial locations

Overseen By Treadwell Therapeutics Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Treadwell Therapeutics, Inc

Must be taking: CDK4/6 inhibitors

Must not be taking: Warfarin, CYP3A4 inducers

Disqualifiers: Pregnancy, Infections, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, CFI-402257, alone and with Fulvestrant in patients with advanced solid tumors and advanced breast cancer. It aims to determine if the drug is safe and effective by studying its effects on the body and cancer cells. Fulvestrant is an established treatment for hormone receptor-positive advanced breast cancer, often used in combination with other therapies to improve outcomes.

Will I have to stop taking my current medications?

The trial requires that you avoid using certain medications, specifically strong CYP3A4 inducers and inhibitors, and some other specific drugs. If you are taking these, you may need to stop or adjust them before joining the trial.

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

Fulvestrant, also known as Faslodex, has been shown to be effective in treating advanced breast cancer, especially in patients who have already received other treatments. It works by blocking and breaking down estrogen receptors, which can help slow the growth of cancer cells. ^{1 2 3 4 5}

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

Fulvestrant (also known as Faslodex) is generally well tolerated in humans, with mild gastrointestinal symptoms being the most common side effect. In a study involving 339 patients, only 5% experienced adverse events, indicating it is generally safe for use in treating advanced breast cancer. ^{1 4 6 7 8}

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

CFI-402257 combined with Fulvestrant is unique because Fulvestrant is a selective estrogen receptor down-regulator (SERD) that targets and degrades estrogen receptors without any agonist effects, offering a new option for women with advanced breast cancer who have become resistant to other treatments like tamoxifen. ^{1 3 4 6 9}

Research Team

R Wesolowski

Principal Investigator

The Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with advanced solid tumors or breast cancer that's positive for estrogen/progesterone receptors but negative for HER2. They must have tried certain therapies before, like a CDK4/6 inhibitor and possibly one line of endocrine therapy or chemotherapy. People can't join if they have brain cancer, serious heart conditions, are pregnant/nursing, had recent treatments/surgery, infections, blood clots or coagulopathy.

Inclusion Criteria

You have breast cancer that is positive for estrogen receptor and/or progesterone receptor, but negative for HER2. You have previously taken a CDK4/6 inhibitor and have received no more than one round of chemotherapy. You have measurable disease based on specific guidelines.

My advanced cancer has worsened despite previous treatment.

I have ER+/PR+ HER2- breast cancer, treated with CDK4/6 inhibitors, and limited prior therapy.

Exclusion Criteria

Are pregnant or nursing

I do not have severe uncontrolled high blood pressure, heart failure symptoms, chest pain, recent heart attack, constant irregular heartbeat, or a long QT interval.

I have been treated with a TTK/MPS1 inhibitor before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Escalation and Expansion

Dose selection and expansion of CFI-402257 as a single agent in advanced solid tumors

48 months

Combination Escalation and Expansion

Dose selection and expansion of CFI-402257 in combination with Fulvestrant in advanced breast cancer

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CFI-402257
• Fulvestrant

Trial Overview The study tests CFI-402257 alone in various advanced cancers and combined with Fulvestrant specifically in advanced breast cancer patients. It aims to determine the safety of these treatments and how well they work against these cancers.

Participant Groups

Group I: Part B: Combination Escalation and Expansion Experimental Treatment 2 Interventions

Dose selection and expansion of CFI-402257 with Fulvestrant

Group II: Part A: Monotherapy Escalation and Expansion Experimental Treatment 1 Intervention

Dose selection and expansion of CFI-402257

Who Is Running the Clinical Trial?

Treadwell Therapeutics, Inc

Lead Sponsor

Trials

4

Recruited

300+

Findings from Research

In a study of 54 postmenopausal women with metastatic breast cancer, fulvestrant demonstrated clinical benefit in 38.9% of patients, with a median time to progression of 6.4 months, indicating its efficacy even after multiple prior treatments.

Fulvestrant was well tolerated, with no severe toxicities (grade 3/4) reported, suggesting it is a safe option for patients with advanced breast cancer who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. Mlineritsch, B., Psenak, O., Mayer, P., et al.[2018]

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]

Fulvestrant was well tolerated and provided clinical benefit to 21% of heavily pre-treated postmenopausal women with advanced breast cancer, with 42% achieving stable disease for at least 12 weeks.

The efficacy of fulvestrant was similar whether given after disease progression or as maintenance therapy, with a median time to progression of 3 months and no significant toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. Catania, C., Ascione, G., Adamoli, L., et al.[2018]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

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]

Fulvestrant is a novel estrogen receptor antagonist used for the palliative treatment of advanced breast cancer in postmenopausal women, and it has no known agonist effects, making it a unique option for therapy.

The drug is well tolerated with mild gastrointestinal symptoms being the most common side effect, and it is administered as a once-a-month intramuscular injection, providing a convenient treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant antiestrogen for treatment of breast cancer. Hancock, CM.[2018]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

In a study of 402 postmenopausal women with advanced breast cancer receiving fulvestrant through a Compassionate Use Program, 29.9% experienced clinical benefits, including partial responses and stable disease for over 6 months.

Fulvestrant was well tolerated, with only 1.5% of patients discontinuing treatment due to adverse events, indicating its safety and potential as an effective option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. Neven, P., Paridaens, R., Pelgrims, G., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme. [2018]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant in heavily pre-treated patients with advanced breast cancer: results from a single compassionate use programme centre. [2018]

4. Spain pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. [2019]

5. 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]

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

Fulvestrant antiestrogen for treatment of breast cancer. [2018]

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

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) in advanced breast cancer: clinical experience from a Belgian cooperative study. [2018]