Fulvestrant +/− Ganetespib for Breast Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: HSP90 inhibitors, Fulvestrant

Disqualifiers: Pregnancy, Brain metastases, Other malignancies, 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

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

Compensation: Varies

Number of Visits: 31

Duration: 38 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding ganetespib to the existing breast cancer treatment, fulvestrant, can more effectively stop cancer cell growth. Fulvestrant (also known as Faslodex) treats hormone receptor-positive breast cancer by blocking estrogen. Ganetespib aims to prevent cancer cells from developing resistance to such treatments. This trial may suit individuals with hormone receptor-positive, metastatic breast cancer that has resisted other endocrine treatments. Participants must be HER2 negative and have previously received up to one line of chemotherapy for this condition. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 other treatments intended to treat your cancer while participating. You must also be at least 2 weeks from your last chemotherapy or radiotherapy.

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

Research shows that both fulvestrant and ganetespib are generally well-tolerated. Fulvestrant, already approved by the FDA for treating breast cancer, did not cause severe side effects in previous research, making it safe for patients with advanced breast cancer.

Studies have also found ganetespib to be well-tolerated. It did not cause significant issues with the heart, liver, or eyes, which are common concerns with new drugs. Some patients experienced mild stomach issues, but these were manageable.

Overall, past research suggests that the combination of fulvestrant and ganetespib is safe. However, individual experiences may vary, so discussing participation with a healthcare provider is important before joining any trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach for treating breast cancer. Fulvestrant is a well-established hormone therapy used to block estrogen receptors, slowing the growth of hormone receptor-positive breast cancer. The combination with Ganetespib is what makes this treatment stand out. Ganetespib is an Hsp90 inhibitor, which targets proteins that help cancer cells survive, potentially enhancing the effectiveness of Fulvestrant. This dual-action approach could offer improved outcomes by attacking the cancer through multiple pathways, something current standard treatments like aromatase inhibitors and other hormone therapies don't do on their own.

What evidence suggests that the combination of fulvestrant and ganetespib could be effective for metastatic breast cancer?

Research has shown that fulvestrant, which participants in this trial may receive, effectively treats advanced hormone receptor-positive breast cancer. Studies have found that it significantly increases progression-free survival, the period during which the cancer does not worsen. On average, fulvestrant alone provides about 14.6 months of progression-free survival.

In this trial, some participants will receive a combination of fulvestrant and ganetespib. Laboratory studies suggest that adding ganetespib to fulvestrant enhances its effectiveness by stopping cancer cells from growing and helping to prevent resistance to treatment. Ganetespib works by blocking HSP90, a protein that cancer cells need to survive. While this combination appears promising in lab studies, its effectiveness in people has not yet been confirmed. ^{1 2 3 4 6}

Who Is on the Research Team?

Nancy U Lin, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with hormone receptor-positive, metastatic breast cancer that's HER2 negative. Participants can have had one prior chemotherapy treatment and must have measurable disease. They should be in good physical condition (ECOG status of 0 or 1) and not currently pregnant or breastfeeding. Those who've previously used fulvestrant or HSP90 inhibitors, have untreated brain metastases, other recent cancers, or severe illnesses are excluded.

Inclusion Criteria

My cancer is not HER2 positive.

You need to have a way to measure the disease for the study.

My breast cancer has not responded to hormone therapy.

Exclusion Criteria

Pregnant or breastfeeding

You are at risk of a severe medical issue, according to the doctor in charge of your treatment.

You have had allergic reactions to drugs similar to fulvestrant or ganetespib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Fulvestrant with or without Ganetespib. Fulvestrant is administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; Ganetespib is administered intravenously on days 1, 8, and 15 of each 28-day cycle.

38 months

Visits every cycle (28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter. Participants were followed for survival up to 4 years from treatment end.

4 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Ganetespib

Trial Overview The study is testing the effectiveness of combining Ganetespib, an HSP90 inhibitor thought to prevent cancer cell resistance, with Fulvestrant, a hormonal therapy approved by the FDA for certain breast cancers. The goal is to see if adding Ganetespib improves outcomes compared to using Fulvestrant alone.

How Is the Trial Designed?

Group I: Arm B - Fulvestrant+Ganetespib Active Control 2 Interventions

Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression.

Group II: ARM A - Fulvestrant Active Control 1 Intervention

Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Published Research Related to This Trial

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 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]

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 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 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]

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, 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]

Citations

1. 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 ...

2. 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; ...

3. 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 ...

4. 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.

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6464820/

Fulvestrant for hormone‐sensitive metastatic breast cancer Our review demonstrates that fulvestrant is a safe and effective systemic therapy and can be considered as a valid option in the sequence of treatments for ...