A Phase IIIb Study to Characterize the Efficacy and Safety of Adjuvant Ribociclib Plus Endocrine Therapy in a Close-to-clinical Practice Patient Population With HR+ HER2- Early Breast Cancer (Adjuvant WIDER)

Plain English Summary

Phase IIIb Study of Ribociclib + ET in Early Breast Cancer is a Phase 3 clinical trial sponsored by Novartis Pharmaceuticals studying Early Breast Cancer. This study is testing a combination of ribociclib with standard hormone therapy (endocrine therapy) for early-stage breast cancer. It is for adults (18+) diagnosed with HR+ HER2- early breast cancer, including certain stages IIA, IIB, and III. Participation involves taking the study drugs and regular check-ups. Some patients may have already started hormone therapy. Standard treatment options for early breast cancer include surgery, radiation, chemotherapy, and hormone therapy. The trial aims to enroll 1400 participants.

Official Summary

The purpose of this open-label, multicenter, phase IIIb, single-arm study is to characterize the efficacy and safety of the combination of ribociclib and standard adjuvant endocrine therapy (ET) on invasive breast cancer-free survival (iBCFS), in a close to clinical practice patient population with HR-positive (HR+), HER2-negative (HER2-), Anatomic Stage Group III, IIB, and a subset of Stage IIA Early Breast Cancer (EBC).

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older and have been diagnosed with HR+ HER2- early breast cancer. You cannot join if you have advanced (Stage IV) breast cancer or if your cancer has returned after surgery. Certain heart conditions or other severe medical issues may prevent participation. Women who are pregnant or breastfeeding cannot join. This trial is studying Early Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to see how many patients remain free of invasive breast cancer for at least 3 years when treated with this new combination. The specific primary outcome measures are: Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years (At 3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial matters because it aims to improve outcomes for patients with early-stage HR+ HER2- breast cancer by evaluating a new combination therapy in a real-world setting. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Early Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial is investigating a targeted therapy (ribociclib) in combination with standard care, suggesting a focus on improving efficacy in a significant patient population within the breast cancer mar Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1400 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, especially regarding your specific stage and type of breast cancer. Understand the study involves taking medication daily and attending regular appointments for monitoring. Be prepared for potential side effects and discuss any concerns with your healthcare team. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 1,400 participants

Interventions

• DRUG: Ribociclib — Ribociclib 400 mg orally once daily on days 1-21 of a 28 day cycle followed by 7 days rest
• DRUG: Letrozole — Letrozole 2.5 mg orally once daily continuously
• DRUG: Ansastrozole — Anastrozole 1 mg orally once daily continuously.
• DRUG: Goserelin — Goserelin administered subcutaneously at 3.6 mg once every 4 weeks if the one-month depot formulation is used or at 10.8 mg once every 3 months if the three-month depot formulation is used
• DRUG: Leuprolide — Leuprolide administered subcutaneously at 3.75 mg once every 4 weeks if the one-month depot formulation is used or at 11.25 mg once every 3 months if the three-month depot formulation is used

Primary Outcomes

• Invasive Breast Cancer Free Survival (iBCFS) rate at 3 years (At 3 years)

Secondary Outcomes

• Incidence and severity of adverse events (AEs) using CTCAE v4.03 (Up to approximately 6 years)
• Invasive Disease-Free Survival (iDFS) (Up to approximately 6 years)
• Distant Disease-Free Survival (DDFS) (Up to approximately 6 years)
• Distant Relapse-Free Survival (DRFS) (Up to approximately 6 years)
• Recurrence-Free Interval (RFI) (Up to approximately 6 years)

Full Eligibility Criteria

Key Inclusion criteria:

* Participant is an adult, male or female ≥ 18 years of age at the time of informed consent form signature (IC).
* Participant has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer (BC) based on the most recently analyzed tissue sample tested by a local laboratory prior to enrollment.
* Participant has HER2- BC defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing based on the most recently analyzed tissue sample.
* Participants may have already received any standard neoadjuvant and/or adjuvant ET, including tamoxifen or toremifene at the time of informed consent signature, but enrollment should occur within 36 months of prior ET start date and participants should have at least 3 years remaining of endocrine adjuvant therapy.
* For participants with prior ET treatment \> 12 months, restaging is highly recommended (unless contradictory to local regulations) to rule out disease recurrence prior to enrollment.
* The number of participants with prior ET between 12 and 36 months will be capped at 30%. The cap will not apply to Black or African American participants.
* Participant has no contraindication to receive adjuvant ET in the study.
* Participant after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories:

  * Anatomic Stage Group III, or
  * Anatomic Stage Group IIB, or
  * A subset of Anatomic Stage Group IIA.
* Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
* Participant has adequate bone marrow and organ function.
* ECG values assessed by KardiaMobile-6L device, or standard 12-lead ECG per local investigator where KardiaMobile-6L cannot be used, as:

  * QTcF interval at Screening \< 450 msec (QT interval using Fridericia's correction).
  * Mean resting heart rate 50-99 beats per minute (determined from the ECG).

Key Exclusion criteria:

* Participant with distant metastases of BC beyond regional lymph nodes (Stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
* Participant is concurrently using other antineoplastic therapy with the exception of adjuvant ET.
* Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol, or limit life expectancy to ≤5 years.
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
* Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
* Women of child-bearing potential (CBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for 21 days after stopping the treatment.

Other inclusion/exclusion criteria may apply

Trial Locations

• Central Alabama Research, Birmingham, Alabama, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Western Reg MC-COH Phoenix, Goodyear, Arizona, United States
• CARTI Cancer Center, Little Rock, Arkansas, United States
• Beverly Hills Cancer Center, Beverly Hills, California, United States
• Onco Inst of Hope and Innovation, Cerritos, California, United States
• City of Hope National Medical, Duarte, California, United States
• Providence Medical Foundation, Fullerton, California, United States
• Palo Alto Medical Foundation, Mountain View, California, United States
• UC Irvine Medical Center, Orange, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Early-Stage Breast Cancer
• Adjuvant Therapy
• Endocrine Therapy
• Oncology
• Cancer Treatment
• Metastatic Breast Cancer (as a condition to exclude)
• Recurrent Breast Cancer (as a condition to exclude)

More Early Breast Cancer Trials

View all Early Breast Cancer clinical trials