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Triple Drug Therapy for HER2 Positive Breast Cancer

Phase 1 & 2

Recruiting

Led By Nicholas P McAndrew

Research Sponsored by Jonsson Comprehensive Cancer Center

Eligibility Criteria Checklist

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

Must have

Creatinine clearance >= 30 mL/min as calculated using the Cockcroft-Gault equation or Serum creatinine =< 1.5 × upper limit of normal (ULN) (within 7 days before enrollment)

Be older than 18 years old

Must not have

Patients with seizure disorder requiring medication

Unable to swallow pills or has significant gastrointestinal disease which would preclude the adequate oral absorption of medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up pre-infusion and 1, 2, 3, and 6 hours after the start of the infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying the side effects and best dose of two drugs, ribociclib and tucatinib, when used with the drug trastuzumab to treat patients with HER2 positive breast cancer. The trial will also compare the effect of the combination of these three drugs with or without the drug fulvestrant to the standard of care for the treatment of patients with early stage breast cancer before surgery.

Who is the study for?

Adults with HER2 positive metastatic breast cancer or early stage breast cancer pre-surgery can join. They need a normal heart function, blood counts within specific ranges, and proper liver and kidney function. Pregnant women can't participate; others must use effective contraception. Excluded are those with recent other cancers, uncontrolled conditions like hypertension, major surgery within the last month, certain drug therapies, infections or heart issues.

What is being tested?

The trial is testing ribociclib and tucatinib's effectiveness in stopping tumor growth when combined with trastuzumab for metastatic cases. It also compares this combo to standard chemotherapy before surgery in early-stage cases. The study will determine the best dose of these drugs and their impact on tumor size reduction.

What are the potential side effects?

Potential side effects include reactions related to blocking enzymes needed for cell growth which may affect organ functions, as well as typical chemotherapy effects such as fatigue, nausea, hair loss and increased risk of infection due to immune system interference.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function, measured by creatinine clearance, is adequate.

Exclusion Criteria

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

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I am on medication for seizures.

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I cannot swallow pills or have a stomach condition that affects medication absorption.

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I have a wound or ulcer that is not healing.

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I haven't taken strong CYP3A4 or CYP2C8 drugs recently.

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My high blood pressure is not controlled, even with medication.

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I do not have uncontrolled heart disease or abnormal heart rhythms.

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I have an autoimmune disease other than Hashimoto's with normal TSH.

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I use oxygen therapy regularly.

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My heart condition does not severely limit my daily activities.

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I am not on high doses of steroids (more than 15 mg of prednisone or equivalent).

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I have an active hepatitis B, hepatitis C, or HIV infection.

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I do not have a serious or uncontrolled infection.

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I have had a bone marrow or organ transplant from another person.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ pre-infusion and 1, 2, 3, and 6 hours after the start of the infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~pre-infusion and 1, 2, 3, and 6 hours after the start of the infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and pre-infusion and 1, 2, 3, and 6 hours after the start of the infusion 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 (MTD) (Phase Ib)

Pathologic complete response (pCR) (Phase II)

Secondary study objectives

Clinical objective response rate (ORR) (Phase IB and II)

Evaluate the pharmacokinetics of ribociclib and tucatinib when given in combination with tucatinib and trastuzumab. (Phase 1b): Area Under Curve (AUC)

Evaluate the pharmacokinetics of ribociclib and tucatinib when given in combination with tucatinib and trastuzumab. (Phase 1b): Average plasma concentration at steady state (Cavg)

+6 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Phase Ib (ribociclib, tucatinib, trastuzumab)Experimental Treatment4 Interventions

Patients receive ribociclib PO QD on days 1-21, tucatinib PO BID on days 1-28, and trastuzumab IV over 30-90 minutes every 7 days. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Phase II,Arm A(ribociclib,tucatinib, trastuzumab, fulvestrant)Experimental Treatment4 Interventions

Patients receive ribociclib PO QD on days 1-21, tucatinib BID on days 1-28, trastuzumab IV over 30-90 minutes every 7 days and fulvestrant subcutaneously (SC) on days 1 and 15 of cycle 1 and day 1 of every subsequent cycle. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Phase II, Arm C (ribociclib, tucatinib, trastuzumab)Experimental Treatment4 Interventions

Patients receive ribociclib PO QD on days 1-21, tucatinib BID on days 1-28, and trastuzumab IV over 30-90 minutes every 7 days. Cycles repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Phase II,Arm B(docetaxel,carboplatin,trastuzumab,pertuzumab)Active Control5 Interventions

Patients receive docetaxel IV over 1 hour on day 1, carboplatin IV on day 1, trastuzumab IV over 30-90 minutes on day 1, and pertuzumab IV over 1 hour on day 1. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab

2014

Completed Phase 4

~5190

Ribociclib

2018

Completed Phase 3

~2420