AZD2014 + Fulvestrant for Breast Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must be taking: Fulvestrant

Must not be taking: Anticancer agents

Disqualifiers: Severe cardiac, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and tolerability of a new combination of treatments for breast cancer. It combines AZD2014, an experimental treatment, with Fulvestrant to assess their effectiveness together in patients with advanced breast cancer that tests positive for estrogen receptors (ER+). This trial may suit those diagnosed with ER+ advanced metastatic breast cancer and have a tumor measurable by scans. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking any chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents, and any investigational agents at least 14 days before starting the study treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the combination of AZD2014 and Fulvestrant is under study for safety and tolerability. Previous studies have examined how patients handle this combination. In one study, patients taking AZD2014 with Fulvestrant generally tolerated it well, though some side effects were reported, which is common with such treatments.

Fulvestrant is already approved for treating certain types of breast cancer, providing some confidence about its safety. It is typically recommended for patients whose cancer has worsened after using an aromatase inhibitor.

AZD2014, however, remains under investigation. Since this trial is in the early stages, the main focus is on ensuring the treatment's safety. Researchers are still determining if any major safety concerns exist.

Overall, while Fulvestrant has a known safety record, the safety of AZD2014 is still being explored. Prospective participants should be aware of potential side effects and discuss them with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD2014 combined with Fulvestrant for breast cancer because this treatment offers a unique approach to tackling the disease. Unlike the standard hormone therapies that primarily focus on blocking estrogen receptors, AZD2014 is an mTOR inhibitor, which targets a different pathway that cancer cells use to grow and survive. By blocking the mTOR pathway, AZD2014 can potentially make cancer cells more susceptible to treatment, possibly leading to improved outcomes. This combined approach could enhance the effectiveness of Fulvestrant, a well-known estrogen receptor degrader, offering new hope for patients with advanced breast cancer.

What evidence suggests that AZD2014 with Fulvestrant could be effective for breast cancer?

Research has shown that using AZD2014 with Fulvestrant, the combination tested in this trial, may help treat certain breast cancers. Studies have found that this combination can stop or even shrink tumors in estrogen receptor-positive (ER+) breast cancer. Fulvestrant is already used for patients with advanced breast cancer that responds to hormones, especially if other treatments have failed. AZD2014 blocks a pathway that cancer cells use to grow, and when combined with Fulvestrant, it enhances the treatment's effectiveness. Early results suggest this combination could be a strong option for advanced breast cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Howard Burris, MD

Principal Investigator

SCRI Development Innovations, LLC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ER+ advanced metastatic breast cancer, who can provide consent and have at least one lesion visible on scans. They must be in good physical condition (ECOG 0 or 1) and not able to bear children. Excluded are those who've had recent cancer treatments, severe heart conditions, major surgery within the last month, minor surgery within two weeks, or uncontrolled type I or II diabetes.

Inclusion Criteria

I have at least one cancer lesion that can be measured by scans.

My breast cancer is ER+ and can be treated with fulvestrant.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had cancer treatments, except for palliative radiotherapy, in the last 14 days.

I have not had major surgery in the last 4 weeks or minor surgery in the last 2 weeks.

I have type 1 diabetes or my type 2 diabetes is not well-controlled (HbA1c > 8%).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD2014 orally in combination with intramuscular Fulvestrant

24 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• AZD2014
• Fulvestrant

Trial Overview The study tests the safety and tolerability of a drug combination: AZD2014 with Fulvestrant for treating ER+ advanced metastatic breast cancer. Participants will receive both medications to evaluate how well they work together.

How Is the Trial Designed?

Group I: AZD2014 with Fulvestrant Experimental Treatment 2 Interventions

AZD2014 with Fulvestrant

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of 423 postmenopausal women with advanced breast cancer, those who progressed on fulvestrant still showed some sensitivity to subsequent endocrine therapies, with 54 patients experiencing clinical benefit from further treatment.

Fulvestrant can be an effective option in the treatment sequence for advanced breast cancer, potentially allowing patients to avoid cytotoxic chemotherapy longer by extending the use of endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. Vergote, I., Robertson, JF., Kleeberg, U., et al.[2019]

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]

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]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

In a presurgical study involving 46 women with ER+ HER2- breast cancer, AZD9496, an oral selective estrogen receptor degrader (SERD), demonstrated biological activity by reducing estrogen receptor (ER) levels, but was not superior to fulvestrant, the standard injectable SERD, in efficacy.

Both AZD9496 and fulvestrant effectively reduced progesterone receptor (PR) and Ki-67 levels, indicating their impact on tumor biology, but no new safety concerns were identified, suggesting that AZD9496 is safe to use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. Robertson, JFR., Evans, A., Henschen, S., et al.[2021]

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 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]

Citations

1. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D2270C00005/

AZD2014 and Fulvestrant in patients with ER+ Advanced ... The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6407749/

Fulvestrant-Based Combination Therapy for Second-Line ... Fulvestrant is recommended for patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) who progress after aromatase inhibitor therapy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02599714

NCT02599714 | Study of AZD2014 and Palbociclib in ... A Phase I/II Multicenter Study of the Combination of AZD2014 and Palbociclib on a Background of Hormonal Therapy in Patients With Locally Advanced/Metastatic ...

4. researchgate.net researchgate.net/publication/270703358_Abstract_P6-12-01_A_phase_I_study_evaluating_AZD2014_in_combination_with_fulvestrant_in_patients_with_ER_advanced_metastatic_breast_cancer

Abstract P6-12-01: A phase I study evaluating AZD2014 in ... This phase I trial assessed the safety, tolerability, pharmacokinetics, and preliminary efficacy of AZD2014 administered in combination with ...

5. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.12958

The therapeutic potential of mTOR inhibitors in breast cancer AZD2014 has been examined in combination with fulvestrant. This combination resulted in tumour growth inhibition or regression in ER+ breast ...

6. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2015-003320-30/results

EudraCT Number 2015-003320-30 - Clinical trial results The amended primary objectives for parts A and B were to investigate the safety and tolerability of the combination of AZD2014 and palbociclib on a background ...