What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving chemotherapy and HER2 receptor inhibition, have several known side effects. Chemotherapy agents like Gemcitabine can cause nausea, vomiting, fatigue, and decreased blood cell counts, leading to infection risk, anemia, and bleeding issues. HER2 receptor inhibitors such as Trastuzumab and Pertuzumab are associated with diarrhea, rash, and potential cardiac dysfunction. Combining these treatments may increase gastrointestinal issues and skin reactions, and requires careful monitoring of heart function due to the risk of cardiac events.

What prior FDA approvals exist?

The FDA has approved several treatments for HER2-positive breast cancer that involve chemotherapy and HER2 receptor inhibition. Trastuzumab (Herceptin) and pertuzumab (Perjeta) are commonly used in combination with chemotherapy agents such as docetaxel and paclitaxel. These combinations have shown significant efficacy in both early and advanced stages of HER2-positive breast cancer. Additionally, the combination of trastuzumab and lapatinib has been approved for patients who have progressed on prior trastuzumab-based therapies. The ongoing study of gemcitabine with trastuzumab and pertuzumab aims to explore further the effectiveness of combining these agents in patients who have previously received trastuzumab and pertuzumab or pertuzumab-based therapy.

What other types of research exist?

Promising novel alternatives for HER2-positive breast cancer treatment include: 1) Tucatinib-Trastuzumab-Capecitabine regimen, which has shown safety and efficacy in treating leptomeningeal metastasis in HER2-positive breast cancer. 2) Trastuzumab Deruxtecan, which has demonstrated significant antitumor activity and safety in patients with previously treated HER2-positive breast cancer, including those with brain metastases. 3) Trastuzumab Emtansine (T-DM1), which has been effective in patients with HER2-positive metastatic breast cancer and central nervous system metastases.

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Anti-metabolites

Gemcitabine + Trastuzumab + Pertuzumab for Breast Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for breast cancer, such as chemotherapy and HER2 receptor inhibition, work through distinct mechanisms. Chemotherapy drugs like Gemcitabine disrupt DNA replication in rapidly dividing cancer cells, causing cell death. HER2 inhibitors, including Trastuzumab and Pertuzumab, target the HER2 protein that is overexpressed in some breast cancers, blocking growth signals and promoting cancer cell death. This combination is crucial for breast cancer patients as it leverages the broad efficacy of chemotherapy with the precision of targeted therapy, potentially improving treatment effectiveness and patient outcomes.

Phase 2

Waitlist Available

Led By Chau Dang, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Histologically documented HER2 (+) breast cancer as defined as IHC 3+ or FISH amplification of ≥ 2.0 of primary or metastatic site; results from the local lab are acceptable

ECOG performance status 0 -1

Must not have

History of prior ≥ G 3 hypersensitivity (HSR) or any toxicity to trastuzumab or pertuzumab that warranted permanent cessation of this agent

History of hepatitis B or C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Approved for 10 Other Conditions

Summary

This trial is testing a combination of three drugs to treat advanced HER2 positive breast cancer in women who have already tried other treatments. The combination includes a chemotherapy drug called gemcitabine and two drugs, trastuzumab and pertuzumab, that stop cancer cells from growing. Pertuzumab was originally developed independently from trastuzumab and later found to work well together when combined with trastuzumab. The goal is to see if this new combination is more effective and safe.

Who is the study for?

This trial is for adults with stage IV HER2-positive breast cancer who've had up to three prior chemotherapies in the metastatic setting and have previously been treated with trastuzumab + pertuzumab or pertuzumab-based therapy. Participants must have a good performance status, stable brain lesions if present, normal heart function, and acceptable blood counts and liver function. Pregnant individuals or those with severe past reactions to study drugs, hepatitis B/C, or recent serious heart issues cannot join.

What is being tested?

The trial is testing a combination of gemcitabine (a standard chemotherapy drug) with two targeted therapies—trastuzumab (Herceptin) and pertuzumab (Perjeta)—to see how effective they are against advanced HER2-positive breast cancer after previous similar treatments. It's a Phase II study focusing on effectiveness as well as safety.

What are the potential side effects?

Potential side effects include reactions related to infusion such as fever or chills; damage to organs like the heart; lowered blood cell counts leading to increased infection risk; fatigue; liver enzyme changes; nausea; and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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My breast cancer is HER2 positive, confirmed by a lab test.

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I am fully active and can carry on all my pre-disease activities without restriction.

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I have been treated with trastuzumab and pertuzumab for my cancer.

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I have stage IV breast cancer that is HER2 positive.

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I have had 3 or fewer chemotherapy treatments for cancer that has spread.

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I am 18 years old or older.

Exclusion Criteria

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

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I had a severe allergic reaction to trastuzumab or pertuzumab.

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I have had hepatitis B or C in the past.

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I haven't had serious heart issues like a heart attack or unstable angina in the last year.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 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

progression free

Secondary study objectives

overall survival

progression-free survival

response

+1 more

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680

51%

Neutropenia

47%

Leukopenia

46%

Nausea

43%

Vomiting

35%

Anaemia

31%

Decreased appetite

26%

Haemoglobin decreased

26%

Fatigue

25%

Constipation

25%

White blood cell count decreased

24%

Neutrophil count decreased

19%

Alanine aminotransferase increased

13%

Platelet count decreased

12%

Rash

10%

Aspartate aminotransferase increased

10%

Thrombocytopenia

Blood sodium decreased

Hypokalaemia

Insomnia

Pyrexia

Hyponatraemia

Blood creatinine increased

Lymphopenia

Diarrhoea

Dyspepsia

Red blood cell count decreased

Cough

Dizziness

Bone marrow failure

Ischaemic stroke

Dyspnoea

Cerebral infarction

Pulmonary embolism

Embolism venous

Superior vena cava syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Gemcitabine Plus Cisplatin (GC)

Pemetrexed Plus Cisplatin (PC)

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

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

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Gemcitabine, Trastuzumab, and PertuzumaExperimental Treatment3 Interventions

The regimen will consist of gemcitabine at 1000mg/m\^2 IV weekly days 1 + 8 q 3 weeks + trastuzumab every 3 weeks (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) + pertuzumab every 3 weeks (840 mg as a loading dose followed by 420 mg every 3 weeks), all given intravenously (IV). Trastuzumab may be given IV weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) in lieu of the every 3 week schedule. A loading dose of trastuzumab will not be required for patients who have received it \< 6 weeks prior to Cycle 1 Day 1.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine

FDA approved

Pertuzumab

FDA approved

Trastuzumab

FDA approved

0 / 9Eligibility 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

Common treatments for breast cancer, such as chemotherapy and HER2 receptor inhibition, work through distinct mechanisms. Chemotherapy drugs like Gemcitabine disrupt DNA replication in rapidly dividing cancer cells, causing cell death. HER2 inhibitors, including Trastuzumab and Pertuzumab, target the HER2 protein that is overexpressed in some breast cancers, blocking growth signals and promoting cancer cell death. This combination is crucial for breast cancer patients as it leverages the broad efficacy of chemotherapy with the precision of targeted therapy, potentially improving treatment effectiveness and patient outcomes.

Heart Failure in Relation to Tumor-Targeted Therapies and Immunotherapies.Targeted therapy for breast cancer in older patients.Pharmacokinetics, clinical indications, and resistance mechanisms in molecular targeted therapies in cancer.