Fulvestrant + Ipatasertib for Breast Cancer

(FINER Trial)

Recruiting at 42 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

250 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Fulvestrant and Ipatasertib for breast cancer?

The CAPItello-291 study showed that combining fulvestrant with an AKT inhibitor like capivasertib significantly improved progression-free survival in certain breast cancer patients. This suggests that a similar combination with Ipatasertib, another AKT inhibitor, might also be effective. ^{1 2 3 4 5}

What safety data exists for Fulvestrant and Ipatasertib in breast cancer treatment?

The safety of Fulvestrant has been evaluated in combination with other drugs like palbociclib and taselisib for breast cancer, showing common side effects such as fatigue, nausea, and infections. No new safety concerns were reported in these studies, suggesting it is generally safe when used with these medications. ^{1 4 6 7 8}

What makes the drug Fulvestrant + Ipatasertib unique for breast cancer treatment?

Fulvestrant is unique because it is an estrogen receptor antagonist that works by blocking estrogen receptors without activating them, making it effective for postmenopausal women with advanced breast cancer who have not responded to other hormone therapies. When combined with Ipatasertib, it may offer a novel approach by potentially enhancing the treatment's effectiveness, although specific details about the combination's unique benefits are not provided in the research. ^{6 9 10 11 12}

What is the purpose of this trial?

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 (Fulvestrant).

Research Team

Stephen Chia

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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 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]

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]

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]

References

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

Capivasertib Doubles PFS in Some Breast Cancers. [2023]

2. England 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. [2022]

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

Anthropometric, clinical and molecular determinants of treatment outcomes in postmenopausal, hormone receptor positive metastatic breast cancer patients treated with fulvestrant: Results from a real word setting. [2022]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study. [2021]

6. United States 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. [2022]

7. United States 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. [2019]

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

Anastrozole plus fulvestrant vs. anastrozole alone for hormone receptor-positive advanced breast cancer: a meta-analysis of randomized controlled trials. [2020]

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

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

10. 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]

11. England 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. [2019]

12. 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]