Fulvestrant + Ipatasertib for Breast Cancer

(FINER Trial)

Not currently recruiting at 44 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

Must be taking: LHRH agonist

Must not be taking: SERDs, PI3K inhibitors

Disqualifiers: CNS metastases, Diabetes, Liver diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a new drug, Ipatasertib, can slow the progression of advanced breast cancer when combined with the standard treatment, Fulvestrant (a hormone therapy). The trial includes two groups: one receives Ipatasertib plus Fulvestrant, while the other receives a placebo (a substance with no treatment effect) instead of Ipatasertib. It seeks women with advanced breast cancer that is estrogen receptor-positive and HER-2 negative, whose cancer has progressed despite previous treatment with specific cancer drugs. Participants should be post-menopausal or have ovarian suppression and must not have received certain other treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other anti-cancer therapy while participating. If you are taking medications for diabetes that require insulin, you may not be eligible for this trial.

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

Studies have shown that using Ipatasertib with Fulvestrant is generally safe for patients. Research indicates that this combination has a manageable safety profile, meaning side effects are usually not severe and can be controlled with proper care.

In previous studies, patients taking Ipatasertib with Fulvestrant experienced common side effects like diarrhea, nausea, and tiredness, but these were typically mild to moderate. Notably, this drug combination significantly slowed the progression of breast cancer compared to using Fulvestrant alone.

While some side effects may occur, the treatment is considered well-tolerated, and many patients manage it well with the right support. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about the combination of Fulvestrant and Ipatasertib for breast cancer because it offers a novel approach by targeting specific pathways. While standard treatments like hormone therapy and chemotherapy focus on hormonal receptors or rapidly dividing cells, Ipatasertib works by inhibiting the Akt pathway, which is crucial for cancer cell survival and growth. This dual mechanism not only tackles the cancer from multiple angles but also holds the promise of overcoming resistance to existing therapies. By combining with Fulvestrant, which blocks estrogen receptors, this treatment strategy could offer improved outcomes for patients with hormone receptor-positive breast cancer.

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

Research has shown that adding Ipatasertib to Fulvestrant can significantly extend the time patients with advanced breast cancer live without their disease worsening, known as progression-free survival (PFS). Patients with hormone receptor-positive breast cancer, in particular, experienced significant benefits. In this trial, some participants will receive the combination of Ipatasertib and Fulvestrant, which proves more effective than Fulvestrant with a placebo. These findings suggest that Ipatasertib, when combined with Fulvestrant, can slow cancer growth more effectively than the standard treatment alone. ^{1 2 3 6 7}

Who Is on the Research Team?

Stephen Chia

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Are You a Good Fit for This Trial?

This trial is for post-menopausal women or those with ovarian suppression, aged 18+, who have advanced ER+ and HER-2 negative breast cancer that has worsened after treatment with CDK 4/6 inhibitors and aromatase inhibitors. They must be in good health otherwise, not on other cancer treatments, and haven't used certain drugs like fulvestrant or PI3K pathway inhibitors.

Inclusion Criteria

I am fully active or can carry out light work.

I am post-menopausal or will use ovarian suppression if pre-menopausal.

There is proof that you have a documented disease from either clinical or radiological exams.

Exclusion Criteria

I have diabetes and need insulin.

My heart's electrical activity (QTc) is 480 msec or more, or I have a family history of long QT syndrome.

I have previously been treated with medications targeting estrogen or the PI3K pathway.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Ipatasertib plus Fulvestrant or placebo plus Fulvestrant to evaluate the control of cancer and assess side effects and safety

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Ipatasertib

Trial Overview The study tests if adding Ipatasertib to the standard therapy Fulvestrant can slow down breast cancer growth. Participants will either receive Ipatasertib plus Fulvestrant or a placebo alongside Fulvestrant to compare effectiveness.

How Is the Trial Designed?

Group I: Ipatasertib + Fulvestrant Experimental Treatment 2 Interventions

Group II: Placebo Placebo Group 2 Interventions

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?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

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]

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 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 phase II study involving 60 postmenopausal women with advanced HER2-negative, hormone receptor-positive breast cancer, the combination of taselisib and fulvestrant showed clinical activity, particularly in patients with PIK3CA mutations, achieving a best confirmed response rate of 38.5%.

The treatment was associated with a high incidence of adverse events, with 50% of patients experiencing grade ≥3 adverse events, but no new safety concerns were identified, indicating that taselisib plus fulvestrant is a potentially safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer. Dickler, MN., Saura, C., Richards, DA., et al.[2019]

In the MONALEESA-3 Phase III trial, ribociclib combined with fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced breast cancer, indicating its efficacy as a treatment option.

Patient-reported outcomes showed that ribociclib maintained health-related quality of life (HRQOL) compared to placebo, with trends suggesting less deterioration in emotional functioning and pain severity, highlighting its potential benefits beyond survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study. Fasching, PA., Beck, JT., Chan, A., et al.[2021]

Fulvestrant (Faslodex) is as effective as anastrozole (Arimidex) for treating advanced breast cancer in postmenopausal women, with similar objective response rates across different patient subgroups.

Both treatments provided comparable clinical benefits, making fulvestrant a valuable option for patients with visceral metastases who have not responded to previous endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Mauriac, L., Pippen, JE., Quaresma Albano, J., et al.[2019]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

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 the phase III SANDPIPER study involving 516 postmenopausal women with PIK3CA-mutant breast cancer, taselisib combined with fulvestrant significantly improved progression-free survival (7.4 months) compared to placebo plus fulvestrant (5.4 months), indicating its efficacy in this patient population.

Despite the efficacy in extending progression-free survival, the taselisib combination had a concerning safety profile, with higher rates of serious adverse events (32.0% vs. 8.9% in placebo) and more treatment discontinuations (16.8% vs. 2.3% in placebo), suggesting limited clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial. Dent, S., Cortés, J., Im, YH., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA1005

A double-blind placebo controlled randomized phase III ... Conclusions: Ipatasertib plus fulvestrant significantly prolongs PFS compared to placebo/fulvestrant in patients with hormone receptor–positive ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12511766/

Pharmacokinetics, safety and tolerability of ipatasertib in ... The combination regimen of ipatasertib 300 mg with palbociclib and fulvestrant had a notable and manageable safety profile, that is generally ...

3. onclive.com onclive.com/view/ipatasertib-plus-fulvestrant-demonstrates-significant-pfs-benefit-in-er-her2-metastatic-breast-cancer

Ipatasertib Plus Fulvestrant Demonstrates Significant PFS ... Ipatasertib in combination with fulvestrant (Faslodex) significantly prolonged progression-free survival (PFS) compared with placebo plus fulvestrant.

4. clinicaltrials.gov clinicaltrials.gov/show/NCT04650581

Fulvestrant and Ipatasertib for Advanced HER-2 Negative ... The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy ( ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT506776

A double-blind placebo controlled randomized phase III ... Ipatasertib plus fulvestrant significantly prolongs PFS compared to placebo/fulvestrant in patients with hormone receptor–positive MBC post progression on 1 st ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04060862

NCT04060862 | A Study of Ipatasertib Plus Palbociclib and ... The open-label Phase Ib portion of this study will evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant.

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/a-study-of-ipatasertib-plus-palbociclib-and-fulvestrant-28505.html

Clinical Trial – Breast Cancer – Safety and Pharmacokinet... Part 1 will confirm that the combination of ipatasertib plus palbociclib and fulvestrant is safe and find the best dose of ipatasertib to be used with ...