Niraparib + Trastuzumab for Breast Cancer

Not currently recruiting at 7 trial locations

Overseen By Erica Stringer-Reasor, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Alabama at Birmingham

Must be taking: Anti-HER2 therapy

Must not be taking: PARP inhibitors, Corticosteroids

Disqualifiers: CNS metastases, BRCA mutations, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for metastatic HER2-positive breast cancer, an aggressive type that grows quickly. The study combines two drugs: Niraparib, a PARP inhibitor that prevents cancer cells from repairing themselves, and Trastuzumab, which targets the HER2 protein. Participants must have metastatic HER2-positive breast cancer and should have experienced progression despite previous HER2-targeted therapies. The goal is to determine if this combination can improve survival rates with minimal side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for prior chemotherapy and hormonal therapy. You must stop any concurrent anti-cancer treatments and certain immunosuppressive therapies before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the safety of using Niraparib and Trastuzumab together for patients with HER2-positive breast cancer. Earlier studies tested Niraparib, which prevents cancer cells from repairing themselves, with Trastuzumab, a drug targeting HER2, to assess their combined effectiveness.

Some patients in these studies experienced side effects, a common occurrence with new treatments. The goal is to achieve a balance where the drugs are effective without causing serious side effects. The study also examines whether lower doses can remain effective and safe. In early treatment stages, researchers are still determining the safest and most effective dose.

Trastuzumab is already approved for treating HER2-positive breast cancer, so its safety is well-established. Niraparib is used for other cancer types, providing some insight into its safety. Overall, the combination undergoes careful testing to ensure it is safe and manageable for patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Researchers are excited about using Niraparib with Trastuzumab for breast cancer because it offers a new way to tackle the disease. Unlike traditional treatments that often focus solely on targeting HER2 receptors, this combination uses Niraparib, a PARP inhibitor, which works by interfering with the cancer cell's ability to repair its DNA, potentially enhancing the effectiveness of Trastuzumab. This dual approach could lead to better outcomes for patients by attacking the cancer on multiple fronts. Additionally, the personalized dosing in later phases based on patient response adds a layer of customization that may improve safety and efficacy.

What evidence suggests that this trial's treatments could be effective for metastatic HER2-positive breast cancer?

This trial will evaluate the combination of Niraparib with Trastuzumab for individuals with HER2-positive breast cancer. Studies have shown that this combination might improve outcomes for this aggressive and challenging-to-treat cancer. Trastuzumab is a well-known treatment targeting HER2, while Niraparib prevents cancer cells from repairing themselves. Early research suggests that this combination could extend patient survival with fewer side effects. Researchers are hopeful because higher concentrations of Niraparib have been found in tumors, potentially increasing its effectiveness. Overall, this treatment could offer a promising new option for those battling this type of breast cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Erica Stringer-Reasor, M.D.

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for women over 18 with aggressive HER2+ metastatic breast cancer who've already tried at least one anti-HER2 therapy. They must be able to take pills, have a heart ejection fraction of ≥50%, and not be pregnant or planning pregnancy during the study. Participants need normal organ/marrow function and measurable disease per RECIST v1.1.

Inclusion Criteria

I can take medicine by mouth.

Signed informed consent

I have tried at least one HER2-targeted therapy for my advanced cancer without success.

Exclusion Criteria

I have received a high dose of doxorubicin or a similar drug.

You have been diagnosed with HIV.

I have recovered from serious side effects of my previous treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive Niraparib and Trastuzumab in varying doses to determine dose-limiting toxicity

6 weeks

Every 3 weeks

Treatment Phase 2

Participants receive the determined dose of Niraparib and Trastuzumab based on Phase 1 results

Up to 100 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Every 6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib
• Trastuzumab

Trial Overview The trial tests Niraparib combined with Trastuzumab in patients with metastatic HER2+ breast cancer to check safety and effectiveness. The goal is to see if this drug combo can improve survival rates while keeping side effects low compared to current treatments.

How Is the Trial Designed?

Group I: Phase 2: Niraparib 200 mg or 100 mg + Trastuzumab 6 mg/kg Experimental Treatment 2 Interventions

The dosage of Niraparib in phase 2 will be determined by the response of patients in Phase 1. A dosage of Niraparib 200 mg will be given along with Trastuzumab 6 mg/kg IV unless a dose limiting toxicity occurs in Phase 1. If so, Niraparib 100 mg will be given with Trastuzumab 6 mg/kg (instead of Niraparib 200 mg).

Group II: Phase 1: Niraparib 200 mg + Trastuzumab 6 mg/kg Experimental Treatment 2 Interventions

In phase 1 patients in this first arm will receive 200 mg Niraparib in combination with 6 mg/kg Trastuzumab given IV every 3 weeks.

Group III: Phase 1: Niraparib 100 mg + Trastuzumab 6 mg/kg Experimental Treatment 2 Interventions

In phase 1 patients in this second arm will receive Niraparib 100 mg in combination with 6 mg/kg Trastuzumab given IV every 3 weeks.

Niraparib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Zejula for:

• Maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy
• Maintenance treatment of adults with platinum-sensitive relapsed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy

Approved in United States as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• Treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status

Approved in Canada as Zejula for:

• Maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

VFoundation

Collaborator

Trials

1

Recruited

50+

The V Foundation

Collaborator

Trials

10

Recruited

320+

Breast Cancer Research Foundation of Alabama

Collaborator

Trials

2

Recruited

70+

Susan G. Komen Breast Cancer Foundation

Collaborator

Trials

68

Recruited

220,000+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Published Research Related to This Trial

In a study of 55 women with HER2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab with chemotherapy resulted in a median progression-free survival (PFS) of 10 months, indicating significant efficacy in this treatment approach.

The treatment was generally safe, with common side effects including neutropenia (40%), leukopenia (34.5%), and thrombocytopenia (32.7%), but serious adverse reactions were relatively low, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab plus pertuzumab in combination with chemotherapy in metastatic HER2-positive breast cancer: a retrospective single-armed cohort study in China. Qian, Y., Peng, Y., Zhou, H., et al.[2022]

Trastuzumab (Herceptin) is a humanized monoclonal antibody that effectively targets the HER2/neu receptor, showing significant antitumor activity in patients with HER2/neu-amplified metastatic breast cancer based on multiple clinical trials.

When used in combination with chemotherapy, trastuzumab enhances treatment outcomes, improving time to progression, response rates, and overall survival, marking it as a pioneering example of targeted therapy in breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Hortobagyi, GN.[2016]

Trastuzumab (Herceptin) combined with endocrine therapy is a promising treatment for women with less aggressive, estrogen receptor/HER2-positive metastatic breast cancer, while for aggressive HER2-positive cases, it significantly improves survival when used with chemotherapy, particularly taxanes.

Trastuzumab has a favorable safety profile, adding little toxicity to taxane chemotherapy, and enhances quality of life compared to chemotherapy alone, making it a viable option for patients who may not tolerate cytotoxic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximizing clinical benefit with trastuzumab. Bell, R., Verma, S., Untch, M., et al.[2019]

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

In a study of 17 patients with advanced HER2/neu overexpressing breast cancer, the combination of trastuzumab and paclitaxel resulted in a response rate of 59%, with 2 complete responses and a median overall survival of 23 months.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced significant toxicities, including hypersensitivity reactions and grade 3 neuropathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

4-years results of weekly trastuzumab and paclitaxel in the treatment of women with HER2/neu overexpressing advanced breast cancer: single institution prospective study. Janku, F., Pribylova, O., Zimovjanova, M., et al.[2015]

Trastuzumab (Herceptin) has demonstrated significant antitumor activity in patients with HER-2-positive metastatic breast cancer, improving response and survival rates when combined with first-line chemotherapy.

Recent clinical trials have focused on new chemotherapy approaches for node-positive breast cancer, laying the groundwork for ongoing studies that incorporate trastuzumab into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. Perez, EA., Hortobagyi, GN.[2015]

HER2-positive breast cancer, which historically had a poor prognosis, can now be effectively treated with a variety of anti-HER2 therapies, significantly improving patient survival rates.

Newly developed treatments, including trastuzumab deruxtecan and trastuzumab emtansine, along with ongoing clinical trials, are expanding options for patients with advanced HER2-positive breast cancer, raising important questions about the best treatment sequences and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. Stanowicka-Grada, M., Senkus, E.[2023]

Niraparib, a recently approved treatment for recurrent platinum-sensitive ovarian cancer, has demonstrated a high oral bioavailability of 72.7% in humans, indicating effective absorption when taken orally.

The study involved six patients who received a therapeutic dose of 300 mg of niraparib, followed by a small intravenous dose to measure its levels in the bloodstream, confirming its potential as a convenient oral treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the absolute oral bioavailability of niraparib by simultaneous administration of a 14C-microtracer and therapeutic dose in cancer patients. van Andel, L., Rosing, H., Zhang, Z., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10452700/

Combination Therapy with Trastuzumab and Niraparib HER2–targeted treatments have improved survival rates in HER2+ breast cancer patients, yet poor responsiveness remains a major clinical ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03368729

Study Details | NCT03368729 | Niraparib in Combination ... Niraparib will be combined with trastuzumab, a HER2-targeted agent, to evaluate the safety and tolerability in patients with metastatic HER2 positive breast ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS1098

Trial in progress: A phase 1b/2 study of the PARP inhibitor ... The study is a phase 1b/2, multicenter, single arm clinical trial evaluating the safety and efficacy of niraparib 200 mg orally days 1-21 with trastuzumab 6 mg ...

4. nature.com nature.com/articles/s43018-022-00400-2

Neoadjuvant study of niraparib in patients with HER2 ... Preliminary pharmacokinetic data showed higher niraparib concentrations in tumors than in plasma, including in BRCA-mut, triple-negative breast ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-07859

PARP Inhibitor (Niraparib) and Trastuzumab for the ... Giving niraparib and trastuzumab together may help to improve survival with few side effects in patients diagnosed with HER2+ metastatic breast cancer.

6. ejhp.bmj.com ejhp.bmj.com/content/30/suppl_1/a194.2

4CPS-129 Real-life effectiveness and safety of niraparib ... On olaparib group, 93.3% of patients experienced an AE. Of these, 20% required temporary discontinuation and 20% required dose reduction due to toxicity. All ...