Samuraciclib + Fulvestrant for Breast Cancer

(SUMIT-BC Trial)

Recruiting at 31 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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of samuraciclib in combination with fulvestrant versus fulvestrant alone in adult participants with metastatic or locally advanced Hormone Receptor (HR) positive and Human Epidermal Growth Factor Receptor (HER)2-negative breast cancer.

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.

What data supports the effectiveness of the drug Samuraciclib + Fulvestrant for breast cancer?

In a study, the combination of Samuraciclib and Fulvestrant showed promising results in patients with hormone receptor-positive, HER2-negative breast cancer, achieving a clinical benefit rate of 36% and partial responses in some patients, indicating potential effectiveness. ^{1 2 3 4 5}

Is the combination of Samuraciclib and Fulvestrant safe for humans?

Fulvestrant, also known as Faslodex, has been shown to be generally safe in humans, with only a small percentage of patients experiencing adverse effects. In studies, it was well tolerated, with very few patients stopping treatment due to side effects. ^{3 6 7 8 9}

How is the drug combination of Samuraciclib and Fulvestrant unique for treating breast cancer?

The combination of Samuraciclib and Fulvestrant is unique because Samuraciclib is a novel drug that may work differently from existing treatments by targeting specific proteins involved in cancer cell growth, while Fulvestrant is an estrogen receptor antagonist that blocks the effects of estrogen on cancer cells. This combination could offer a new approach for patients who have progressed on other endocrine therapies. ^{1 3 7 9 10}

Eligibility Criteria

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

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.

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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 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 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]

References

1. England 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). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Dose escalation and expansion cohorts in patients with advanced breast cancer in a Phase I study of the CDK7-inhibitor samuraciclib. [2023]

3. England 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. [2023]

4. England 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. [2022]

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

PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients. [2023]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

8. Korea (South) 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. [2021]

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

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

10. India pubmed.ncbi.nlm.nih.gov

Fulvestrant: a review of its development, pre-clinical and clinical data. [2007]