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Tyrosine Kinase Inhibitor

Combination Chemotherapy for Breast Cancer

Phase 1 & 2

Waitlist Available

Led By Rachel Layman

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Histological confirmation of breast cancer

Cohort 1: Phase II: patient must have HER2+ (regardless of hormonal receptor status) stage III IBC or Stage IV IBC if the metastatic sites are amenable for local therapy (i.e. radiation and/ or surgery) and will have breast surgery

Must not have

Excisional biopsy or lumpectomy for the current breast cancer

Any other previous malignancies (except for cervical in situ cancers treated only by local excision, and basal and squamous cell carcinomas of the skin) within 5 years

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 84 days (course 4)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing neratinib, pertuzumab, trastuzumab, and paclitaxel as possible treatments for metastatic breast cancer.

Who is the study for?

This trial is for adults with confirmed breast cancer that has spread and who can take oral meds. They must have good heart function, normal blood counts, liver function within certain limits, and agree to use birth control. It's not for those breastfeeding, with a history of certain autoimmune diseases or other recent cancers, uncontrolled high blood pressure, serious infections or hepatitis B/C.

What is being tested?

The study tests neratinib combined with paclitaxel chemotherapy and possibly pertuzumab and trastuzumab before more chemo. The goal is to find the best dose of neratinib and see how well it works in stopping tumor growth when used with these drugs in metastatic or locally advanced breast cancer.

What are the potential side effects?

Possible side effects include diarrhea from neratinib; allergic reactions, nerve damage from paclitaxel; heart issues from trastuzumab; infusion reactions from pertuzumab; plus typical chemo effects like fatigue, hair loss (from doxorubicin), risk of infection (due to low white cells), bleeding risks (low platelets) from cyclophosphamide.

Eligibility Criteria

Inclusion Criteria

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

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My breast cancer diagnosis was confirmed through tissue examination.

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I have HER2+ stage III or IV inflammatory breast cancer and can undergo surgery or radiation.

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My heart's pumping ability is confirmed to be good by a recent test.

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I can carry out all my usual activities without help.

Exclusion Criteria

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

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I had surgery to remove part or all of my breast tumor.

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I haven't had any cancer except for some skin cancers and treated cervical cancer in the last 5 years.

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I am currently breastfeeding or plan to become pregnant during treatment.

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I have hepatitis B or C and my liver tests are abnormal.

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I have a condition that significantly affects my stomach or intestines.

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I have had ongoing diarrhea of moderate severity.

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My blood pressure is not higher than 150/90 mmHg, even with medication.

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I do not have serious heart problems or a history of such conditions.

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I have moderate to severe numbness, tingling, or muscle weakness.

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I have an ongoing infection or need long-term antibiotics.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 84 days (course 4)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 84 days (course 4)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 84 days (course 4) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Maximum tolerated dose of neratinib, pertuzumab, trastuzumab and paclitaxel treatment defined as dose limiting toxicities of grade 3 or higher

Pathologic complete response (pCR) rate determined by pCR in breast and axillary lymph nodes (pCR breast & nodes) in HER2+ and HER2-/hormone receptor (HR)+ inflammatory breast cancer treated with neratinib-based treatment

Secondary study objectives

Incidence of adverse events of combination therapy

Side effects data

From 2022 Phase 2 trial • 11 Patients • NCT03094052

100%

Diarrhea

100%

Constipation

82%

Nausea

45%

Abdominal distension

45%

Fatigue

36%

Dizziness

36%

Headache

27%

Hot flashes

27%

Dyspnea

27%

Anorexia

27%

Vomiting

27%

Pruritus

27%

Weight loss

18%

Skin and subcutaneous tissue disorders - Other, specify

18%

Dysgeusia

18%

Bloating

18%

Fever

18%

Abdominal pain

18%

Gastrointestinal disorders - Other, specify

18%

Aspartate aminotransferase increased

18%

Alanine aminotransferase increased

18%

Sinus bradycardia

Lymphedema

Neck pain

Rash acneiform

Rash maculo-papular

Muscle weakness upper limb

Vaginal dryness

Back pain

Anal hemorrhage

Paresthesia

Gastroesophageal reflux disease

Pain

Infections and infestations - Other, specify

Urinary tract pain

Flu like symptoms

Fracture

Flatulence

Mucositis oral

Chills

General disorders and administration site conditions - Other, specify

Ejection fraction decreased

Oral dysesthesia

Peripheral sensory neuropathy

Creatinine increased

Upper respiratory infection

Vaginal infection

Stomach pain

Bruising

Fall

Joint range of motion decreased

Musculoskeletal and connective tissue disorder - Other, specify

Arthralgia

Vaginal discharge

Vaginal hemorrhage

Wheezing

Anxiety

Insomnia

Cholecystitis

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Neratinib)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Group C (Cohort 2)Experimental Treatment5 Interventions

Patients receive neratinib PO QD on days 1-21, paclitaxel IV over 1-3 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery/ Patients then receive doxorubicin and cyclophosphamide as in Group B. Patients then undergo standard of care surgery.

Group II: Group B (Cohort 1 Phase II)Experimental Treatment7 Interventions

Patients receive neratinib, paclitaxel, pertuzumab, and trastuzumab as in Group A. Patients then receive doxorubicin IV and cyclophosphamide IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.

Group III: Group A (Cohort 1 Phase Ib)Experimental Treatment5 Interventions

Patients receive neratinib PO QD on days 1-21, paclitaxel IV over 1-3 hours on days 1, 8, and 15, pertuzumab IV over 1 hour on day 1, and trastuzumab IV over 1-2 hours on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression or excessive toxicity with metastatic disease may receive up to 4 additional courses and with locally advanced disease may receive up to 2 additional courses.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab

2014

Completed Phase 4

~5190

Pertuzumab

2014

Completed Phase 3

~7500