Samuraciclib + Fulvestrant for Breast Cancer

(SUMIT-BC Trial)

No longer recruiting at 43 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Carrick Therapeutics Limited

Must be taking: LHRH agonists

Disqualifiers: Inflammatory breast cancer, active malignancy, 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: Up to 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for hormone receptor-positive, HER2-negative breast cancer. Researchers aim to determine if adding samuraciclib (an experimental treatment) to fulvestrant enhances effectiveness compared to fulvestrant alone. Participants who have experienced disease progression after specific prior treatments and know their TP53 mutation status might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in breast cancer therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Earlier studies have shown promising safety results for the combination of samuraciclib and fulvestrant. Research suggests that this drug combination was safe for individuals with hormone receptor-positive, HER2-negative breast cancer. These patients had undergone multiple treatments, yet the combination still yielded positive results.

Fulvestrant alone is a well-known treatment, used safely in many with hormone receptor-positive breast cancer. Studies have shown it is generally well-tolerated, making it a reliable option for many.

Overall, previous research has demonstrated encouraging safety profiles for both treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about samuraciclib combined with fulvestrant for breast cancer because it offers a novel approach by targeting CDK7, a key protein in cancer cell growth. Unlike standard treatments that often focus on hormone receptors or HER2, samuraciclib's mechanism disrupts the cancer cell cycle more directly, potentially enhancing effectiveness. Additionally, administering samuraciclib in varying cycle lengths alongside fulvestrant aims to optimize patient outcomes and manage resistance, offering hope for improved treatment strategies.

What evidence suggests that this trial's treatments could be effective for breast cancer?

This trial will evaluate the effectiveness of samuraciclib and fulvestrant in treating hormone receptor-positive (HR+) breast cancer. Research has shown that samuraciclib, when combined with fulvestrant, can help treat HR+ breast cancer, with studies finding that this combination helps patients live longer without their cancer worsening. In this trial, some participants will receive samuraciclib with fulvestrant, while others will receive fulvestrant alone. Fulvestrant alone has already proven effective for advanced HR+ breast cancer, with some studies showing patients live without cancer progression for about 14.6 months. Together, samuraciclib and fulvestrant show promise, especially for those who have had previous treatments. Participants without specific genetic changes (TP53 mutations) or cancer spread to the liver seem to benefit the most from the combination. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults with HR-positive, HER2-negative advanced or metastatic breast cancer who've had prior AI and CDK4/6i therapy can join. They must have measurable disease, be in fairly good health (ECOG ≤1), not severely ill from other causes, and expected to live more than 12 weeks. Pre/peri-menopausal participants should be on LHRH agonists for at least 4 weeks.

Inclusion Criteria

My cancer worsened during or within 6 months after my last treatment.

Participants must have a way to measure their disease, like a tumor or bone disease, according to specific guidelines.

Expected life expectancy of >12 weeks in the judgement of the treating investigator.

Exclusion Criteria

I have had more than one hormone therapy for my advanced cancer.

I haven't had any cancer except for certain skin cancers or cervical pre-cancer in the last 3 years.

My liver, kidneys, and bone marrow are not working well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive samuraciclib in combination with fulvestrant or fulvestrant alone. Samuraciclib is administered in cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9), and up to 84 days (Cycles 10 onwards). Fulvestrant is administered monthly with an additional dose at Cycle 1 Day 15.

Up to 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and progression-free survival.

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they benefit from the study drug.

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Samuraciclib

Trial Overview

The trial is testing the effectiveness of Samuraciclib combined with Fulvestrant versus just Fulvestrant alone in treating certain advanced breast cancers. It aims to see if adding Samuraciclib helps patients better than the standard treatment.

How Is the Trial Designed?

Group I: Arm C Experimental Treatment 1 Intervention

Participants will receive fulvestrant administered monthly, plus additional dose at Cycle 1 Day 15.

Group II: Arm B Experimental Treatment 2 Interventions

Participants will receive 240 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15.

Group III: Arm A Experimental Treatment 2 Interventions

Participants will receive 360 mg of samuraciclib on cycles of 28 days (Cycle 1 to 6), 56 days (Cycle 7 to 9) and up to 84 days (Cycles 10 onwards in combination with fulvestrant administered monthly, plus an additional dose at Cycle 1 Day 15.

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Carrick Therapeutics Limited

Lead Sponsor

Trials

5

Recruited

290+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In the PALOMA-3 trial, Korean patients with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer treated with palbociclib plus fulvestrant experienced a significantly longer median progression-free survival (PFS) of 12.3 months compared to 5.4 months for those on placebo plus fulvestrant.

Palbociclib was generally safe, with neutropenia being the most common side effect, and it showed a confirmed objective response rate of 21.1% compared to 11.8% for the placebo group, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Plus Fulvestrant in Korean Patients from PALOMA-3 With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Kim, JH., Im, SA., Sim, SH., et al.[2021]

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 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

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]

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]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

Citations

1.

nature.com

nature.com/articles/s41598-021-83622-1

Real-world data of fulvestrant as first-line treatment ...

Effectiveness outcomes. With a median follow-up period of 31.4 months, the median PFS with fulvestrant was 14.6 months (95% CI 10.9–19.9 months; ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial

In 2016, FALCON met its primary end point, demonstrating significant improvement in progression-free survival (PFS) with fulvestrant 500 mg ...

3.

astrazeneca-us.com

astrazeneca-us.com/media/press-releases/2022/capivasertib-plus-faslodex-fulvestrant-reduced-the-risk-of-disease-progression-or-death-by-40-versus-faslodex-in-advanced-hr-positive-breast-cancer-12082022.html

Capivasertib plus FASLODEX® (fulvestrant) reduced the ...

Results showed capivasertib in combination with FASLODEX demonstrated a 40% reduction in the risk of disease progression or death versus placebo plus FASLODEX.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9984913/

Retrospective Evaluation of Fulvestrant Efficacy and ...

In the literature, the CONFIRM study reported that the efficacy of 500 mg fulvestrant was higher than 250 mg, and the subsequent phase II FIRST ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8391338/

Efficacy of Fulvestrant in Women with Hormone-Resistant ...

Our results show that fulvestrant is effective in both early- and later-line therapy in advanced HR+ breast cancer. Likewise, women with both primary and ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7545684/

Efficacy and Safety of Fulvestrant 500mg in Hormone ...

Conclusion: Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2˗ metastatic breast cancer.