Ovarian Suppression + Tamoxifen/Exemestane for Breast Cancer

(SOFT Trial)

No longer recruiting at 510 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: International Breast Cancer Study Group

Must not be taking: GnRH analogues, SERMs, HRT

Disqualifiers: Postmenopausal, Metastatic disease, Inoperable cancer, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if suppressing ovarian function combined with either tamoxifen or exemestane (also known as Aromasin, a type of hormone therapy) is more effective than tamoxifen alone in preventing the recurrence of hormone-responsive breast cancer. The trial focuses on premenopausal women who have undergone surgery for hormone-sensitive breast cancer. Ideal candidates are those who have not experienced menopause and have had surgery for hormone-receptive breast cancer without metastasis. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are currently on endocrine therapy, you may continue it until the trial's specified treatment begins. It's best to discuss your specific medications with the trial team.

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

Research has shown that both tamoxifen and exemestane, when combined with treatments that lower ovarian function, are safe for treating breast cancer. Tamoxifen, a well-known medication, has been used for many years and is generally well-tolerated, though some patients report side effects like hot flashes and an increased risk of blood clots.

Exemestane, when used with treatments that lower ovarian function, has also been studied. Research found it generally safe for premenopausal women with breast cancer. Some patients report side effects such as joint pain and hot flashes, but these are usually manageable.

Overall, both treatments have a history of safe use in breast cancer patients. They have been studied in large groups, providing extensive safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine hormone therapy with ovarian function suppression in new ways to tackle breast cancer. While Tamoxifen is a well-known treatment that blocks estrogen from fueling cancer growth, pairing it with ovarian suppression techniques like triptorelin injections, surgical oophorectomy, or ovarian irradiation could enhance its effectiveness by further reducing estrogen levels. Exemestane, typically used post-menopause, is being tested in premenopausal women alongside ovarian suppression, offering a novel approach to minimize estrogen production. These combinations aim to improve outcomes by targeting estrogen more comprehensively, potentially offering better protection against cancer recurrence.

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

This trial will compare different treatment approaches for breast cancer. Research has shown that adding ovarian function suppression (OFS) to tamoxifen, which participants in one arm of this trial may receive, can help treat breast cancer. The ASTRRA trial found that using tamoxifen with OFS significantly improved the time patients stayed free from the disease in certain cases. However, some studies reported more side effects, such as menopause symptoms, with this combination.

For exemestane with OFS, another treatment option in this trial, studies have shown encouraging results. Specifically, one study found that this combination had a 92.8% rate of patients remaining free from breast cancer after five years, compared to 88.8% for tamoxifen alone. This suggests that exemestane with OFS might be more effective in preventing cancer recurrence. ^{1 2 6 7 8}

Who Is on the Research Team?

Gini Fleming

Principal Investigator

ETOP IBCSG Partners Foundation

Are You a Good Fit for This Trial?

This trial is for premenopausal women who have had surgery for hormone-responsive breast cancer. They must be within 8 months post-chemotherapy, with no prior invasive breast cancer or current metastatic disease. Participants need to agree to data and tissue handling guidelines and complete quality of life forms if required by the study group.

Inclusion Criteria

Patients must have completed baseline Quality of Life (QL) Forms prior to randomization

Patients must be accessible for follow-up

Patients must be informed of and agree to data and tissue material transfer and handling

Exclusion Criteria

My cancer has spread to distant parts of my body.

I have had cancer before, but it fits the exceptions.

I became postmenopausal after surgery or chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tamoxifen or exemestane with ovarian function suppression for 5 years

5 years

Monthly visits for injections, annual visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 1 year, every 6 months for 5 years, then annually

Quality of Life Assessment

Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 4 years

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Exemestane
• Oophorectomy
• Tamoxifen
• Triptorelin

Trial Overview The trial tests ovarian suppression using tamoxifen alone versus in combination with exemestane or triptorelin, aiming to reduce estrogen production that can stimulate tumor growth. It's a phase III randomized study comparing these treatments' effectiveness in preventing breast cancer recurrence.

How Is the Trial Designed?

Group I: T+OFS Experimental Treatment 6 Interventions

Tamoxifen 20mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)

Group II: E+OFS Experimental Treatment 6 Interventions

Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)

Group III: Tamoxifen Active Control 3 Interventions

Tamoxifen 20mg orally daily for 5 years

Exemestane is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in United States as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in Canada as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Approved in Japan as Aromasin for:

• Early breast cancer
• Advanced breast cancer

Who Is Running the Clinical Trial?

International Breast Cancer Study Group

Lead Sponsor

Trials

29

Recruited

25,100+

ETOP IBCSG Partners Foundation

Lead Sponsor

Trials

66

Recruited

58,200+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

NSABP Foundation Inc

Collaborator

Trials

89

Recruited

140,000+

Breast International Group

Collaborator

Trials

34

Recruited

53,600+

Cancer and Leukemia Group B

Collaborator

Trials

81

Recruited

118,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

NCIC Clinical Trials Group

Collaborator

Trials

190

Recruited

145,000+

Southwest Oncology Group

Collaborator

Trials

389

Recruited

260,000+

North Central Cancer Treatment Group

Collaborator

Trials

49

Recruited

81,100+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1404037

Adjuvant Exemestane with Ovarian Suppression in ... The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane–ovarian suppression group, as compared with 88.8% in the tamoxifen ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12360005/

Evaluation and management of incomplete ovarian function ... The trials were designed to determine the impact of ovarian function suppression (OFS) in women receiving adjuvant tamoxifen and whether ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00066690

Study Details | NCT00066690 | Suppression of Ovarian ... This randomized phase III trial studies ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2816030

Adjuvant Ovarian Function Suppression in Premenopausal ... Findings This cohort study of 2647 individuals with premenopausal, early-stage breast cancer diagnoses found no significant recurrence risk ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1803164

Tailoring Adjuvant Endocrine Therapy for Premenopausal ... Among the patients who were assigned to receive exemestane plus ovarian suppression, the rate of disease-free survival was 85.9%, a difference ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10938175/

Adjuvant Ovarian Function Suppression in Premenopausal ... This population-based cohort study included all premenopausal, early-stage breast cancer diagnoses between 2010 and 2020 in Alberta, Canada.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00066703

Study Details | NCT00066703 | Triptorelin With Either ... Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the use of estrogen. It is not yet known whether giving ...

8. ascopubs.org ascopubs.org/doi/10.1200/OP-24-00502

Clinical Management of Ovarian Function Suppression in ... We designed a questionnaire to determine the choice of GnRHa, schedule, duration, initiation, use of bone modifiers, and monitoring of estradiol (E2).