What is the mechanism of action of this treatment?

Ribociclib is a CDK4/6 inhibitor that blocks proteins essential for cell cycle progression, thereby halting cancer cell proliferation. Bicalutamide is an androgen receptor antagonist that prevents androgens from stimulating cancer cell growth. These mechanisms are crucial for patients with androgen receptor-positive breast cancer, as they target specific pathways involved in cancer growth, leading to more personalized and effective treatments.

What side effects are associated with this type of intervention?

CDK4/6 inhibitors, such as Ribociclib, commonly cause side effects including neutropenia, leukopenia, fatigue, nausea, diarrhea, and liver enzyme abnormalities. Androgen receptor antagonists like Bicalutamide can lead to gynecomastia, hot flashes, gastrointestinal disturbances, and liver function changes. Both classes of drugs require careful monitoring due to their potential impact on blood counts and liver function.

What prior FDA approvals exist?

CDK4/6 inhibitors such as Ribociclib, Palbociclib, and Abemaciclib have been FDA-approved for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. These drugs inhibit cyclin-dependent kinases 4 and 6, thereby preventing cell cycle progression. While androgen receptor antagonists like Bicalutamide are primarily used in prostate cancer, they are being studied in clinical trials for androgen receptor-positive triple-negative breast cancer.

What other types of research exist?

Promising novel alternatives for breast cancer treatment in 2024 include PARP inhibitors like Olaparib and Talazoparib, especially for patients with BRCA mutations. Immunotherapies such as Pembrolizumab (a PD-1 inhibitor) have also shown efficacy in certain subtypes of breast cancer. Additionally, antibody-drug conjugates like Trastuzumab Deruxtecan are emerging as effective treatments for HER2-positive breast cancer.

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Antiandrogen

Ribociclib + Bicalutamide for Breast Cancer

Phase 1 & 2

Recruiting

Led By Kari Wisinski, MD

Research Sponsored by Ruth O'Regan, M.D.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Able to swallow bicalutamide and ribociclib capsules/tablets

Age ≥ 18 years at the time of consent

Must not have

Received radiotherapy <14 days prior to registration and not recovered to grade 1 or better from related side effects

Had major surgery within 14 days prior to registration or not recovered from major side effects of the surgery

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the combination of ribociclib and bicalutamide in patients with advanced AR+ triple-negative breast cancer. The drugs aim to stop cancer growth by blocking hormones and proteins that the cancer cells need to multiply.

Who is the study for?

This trial is for adults with advanced AR+ triple-negative breast cancer who haven't had certain treatments, have no active brain metastases, and whose major organs function well. They must not be pregnant or breastfeeding, agree to use contraception, and can swallow pills. Excluded are those with recent heart issues, strokes, uncontrolled conditions that could affect safety or compliance, known HIV infection or other active cancers needing treatment.

What is being tested?

The study tests ribociclib in combination with bicalutamide on patients with a specific type of breast cancer (AR+ TNBC). It's an open-label phase II trial without randomization or blinding. Participants will receive both drugs to see how effective this combo is against their cancer.

What are the potential side effects?

Potential side effects include nausea, fatigue, low blood counts leading to increased infection risk or bleeding problems; liver issues; potential heart rhythm problems; allergic reactions; and possible interactions with other medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can swallow pills.

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I am 18 years old or older.

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My breast cancer is triple-negative and cannot be surgically removed, but tests show it is AR positive.

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I do not have cancer that has spread to my brain or spinal cord.

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My heart's electrical activity is normal, with a safe QT interval and resting rate.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I had radiotherapy less than 2 weeks ago and still have side effects.

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I have not had major surgery or recovered from its major side effects within the last 14 days.

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I have a digestive condition that affects how my body absorbs medication.

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I have been diagnosed with HIV.

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I have Long QT syndrome or a family history of sudden death.

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I am taking medication that affects my heart's rhythm and cannot stop.

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I have cirrhosis with a moderate to severe liver function impairment.

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I have severe heart failure or my heart's pumping ability is reduced (LVEF <50%).

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I haven't had serious heart rhythm problems in the last year.

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I am currently taking warfarin or a similar blood thinner.

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I have another cancer that is growing and needs treatment.

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I do not have any serious wounds, ulcers, or unhealed bone fractures.

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I have had a heart attack or other heart issues in the last 6 months.

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I have previously been treated with hormone therapies for cancer.

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I haven't taken any experimental drugs recently.

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I am currently on medication for an infection.

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I am not taking strong drugs affecting liver enzymes that can't be stopped a week before starting the study drug.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase I: Maximum Tolerated Dose

Phase II: Clinical benefit rate (CBR) of treatment combination

Secondary study objectives

Phase I: Assess Safety and Tolerability By summarizing counts and percentages grade 3-5 adverse events (NCI CTCAE Version 4)

Phase I: Duration of Response

Phase I: Objective Response Rate (ORR)

+6 more

Side effects data

From 2020 Phase 3 trial • 502 Patients • NCT03096847

46%

NEUTROPENIA

43%

NAUSEA

38%

FATIGUE

33%

ALOPECIA

25%

NASOPHARYNGITIS

20%

LEUKOPENIA

20%

DIARRHOEA

20%

ASPARTATE AMINOTRANSFERASE INCREASED

19%

ARTHRALGIA

19%

ALANINE AMINOTRANSFERASE INCREASED

18%

CONSTIPATION

18%

ANAEMIA

17%

HEADACHE

17%

VOMITING

15%

NEUTROPHIL COUNT DECREASED

15%

STOMATITIS

14%

INSOMNIA

13%

PAIN IN EXTREMITY

13%

BACK PAIN

13%

DYSPNOEA

12%

HOT FLUSH

11%

THROMBOCYTOPENIA

11%

RASH

11%

OEDEMA PERIPHERAL

11%

DECREASED APPETITE

10%

URINARY TRACT INFECTION

10%

WHITE BLOOD CELL COUNT DECREASED

10%

COUGH

10%

PRURITUS

ELECTROCARDIOGRAM QT PROLONGED

DYSPEPSIA

VERTIGO

MUSCULOSKELETAL PAIN

DRY SKIN

GAMMA-GLUTAMYLTRANSFERASE INCREASED

LACRIMATION INCREASED

ABDOMINAL PAIN UPPER

WEIGHT DECREASED

ABDOMINAL PAIN

PYREXIA

BLOOD CREATININE INCREASED

BONE PAIN

DRY MOUTH

ERYTHEMA

DRY EYE

DIZZINESS

SLEEP DISORDER

HYPERTENSION

MYALGIA

CYSTITIS

DYSGEUSIA

DEPRESSION

GENERAL PHYSICAL HEALTH DETERIORATION

BRONCHITIS

MUSCULOSKELETAL CHEST PAIN

POLYNEUROPATHY

SEASONAL ALLERGY

PLEURAL EFFUSION

HYPOCALCAEMIA

URETEROLITHIASIS

SKIN ULCER

ARTHROPOD BITE

GASTROINTESTINAL INFECTION

OROPHARYNGEAL PAIN

INFLUENZA

DEVICE RELATED INFECTION

METASTASES TO SPINE

CHEST PAIN

CYSTITIS ESCHERICHIA

SEPSIS

INCISIONAL HERNIA

COLON CANCER

METASTASES TO BONE

PULMONARY EMBOLISM

ATRIAL FIBRILLATION

ANAL HAEMORRHAGE

HELICOBACTER GASTRITIS

TUMOUR LYSIS SYNDROME

TUMOUR PAIN

WEIGHT INCREASED

PANIC ATTACK

FLANK PAIN

SPINAL PAIN

FEBRILE NEUTROPENIA

CARDIAC FAILURE

ILEUS

INTESTINAL STRANGULATION

COMPLICATION OF DEVICE INSERTION

IMPAIRED HEALING

PAIN

HEPATIC CIRRHOSIS

ABSCESS JAW

APPENDICITIS

MASTITIS

PNEUMONIA

HIP FRACTURE

JAW FRACTURE

RADIUS FRACTURE

BLOOD BILIRUBIN INCREASED

HYPERCALCAEMIA

HYPERKALAEMIA

DEVICE LOOSENING

RENAL FAILURE

RENAL IMPAIRMENT

CIRCULATORY COLLAPSE

TOOTHACHE

BLOOD LACTATE DEHYDROGENASE INCREASED

HYPOAESTHESIA

HYPERFIBRINOLYSIS

DRUG-INDUCED LIVER INJURY

ABDOMINAL PAIN LOWER

DEHYDRATION

OSTEITIS

100%

80%

60%

40%

20%

Study treatment Arm

Ribociclib + Letrozole Cohort B2

Ribociclib + Letrozole Cohort A

Ribociclib + Letrozole Cohort B1

Total

Ribociclib + Letrozole Cohort B

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Arm A - Phase IExperimental Treatment2 Interventions

Dose Escalation Cohort 1 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 400mg PO daily on days 1-21 of a 28 day cycle. Cohort 2 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 400mg PO daily on days 1-28 of a 28 day cycle. Cohort 3 will consist of 3-6 patients who will receive bicalutamide 150mg PO daily on days 1-28 of a 28 day cycle and ribociclib 600mg PO daily on days 1-21 of a 28 day cycle. Experimental: Arm B - Phase II Investigational Treatment The maximum safe dose of ribociclib in combination with bicalutamide will be given to up to 25 patients.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bicalutamide

2003

Completed Phase 3

~6210

ribociclib

2023

Completed Phase 3

~630

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ribociclib is a CDK4/6 inhibitor that blocks proteins essential for cell cycle progression, thereby halting cancer cell proliferation. Bicalutamide is an androgen receptor antagonist that prevents androgens from stimulating cancer cell growth. These mechanisms are crucial for patients with androgen receptor-positive breast cancer, as they target specific pathways involved in cancer growth, leading to more personalized and effective treatments.