Niraparib + Trastuzumab for Breast Cancer

Recruiting at 6 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

46 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Niraparib and Trastuzumab for breast cancer?

Trastuzumab, a part of the treatment, has shown significant effectiveness in improving survival rates and reducing tumor progression in HER2-positive breast cancer when combined with chemotherapy. This suggests potential benefits when used in combination with other drugs like Niraparib. ^{1 2 3 4 5}

Is the combination of Niraparib and Trastuzumab safe for humans?

Trastuzumab has been studied for safety in breast cancer treatments, often combined with other drugs, and is generally considered safe, though it can have side effects like heart issues. Niraparib has been approved for other cancers and has shown a tolerable safety profile, but specific safety data for the combination of Niraparib and Trastuzumab in breast cancer is not available. ^{6 7 8 9 10}

What makes the drug combination of Niraparib and Trastuzumab unique for breast cancer treatment?

The combination of Niraparib and Trastuzumab is unique because it combines a PARP inhibitor (Niraparib) with a monoclonal antibody (Trastuzumab) targeting HER2-positive breast cancer, potentially offering a novel approach by leveraging different mechanisms of action to enhance treatment efficacy. ^{2 11 12 13 14}

What is the purpose of this trial?

The human epidermal growth factor receptor 2 (HER2) regulates cell growth and survival. Approximately 15-20% of all breast cancers are HER2-positive, which are an aggressive and fast-growing subtype of breast cancer. This study will evaluate a new treatment using a potent Poly polymerase (PARP) inhibitor known as Niraparib. Niraparib will be combined with trastuzumab, a HER2-targeted agent, to evaluate the safety and tolerability in patients with metastatic HER2 positive breast cancer. It is anticipated that the combination of drugs will improve survival and have few side effects.

Research Team

Erica Stringer-Reasor, M.D.

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Anti-HER2 Drugs for the Treatment of Advanced HER2 Positive Breast Cancer. [2023]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Targeting the human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer: recent advances and future directions. [2019]

5. England pubmed.ncbi.nlm.nih.gov

High efficacy of pre-operative trastuzumab combined with paclitaxel following doxorubicin & cyclophosphamide in operable breast cancer. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. [2018]

7. France 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. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Buparlisib in breast cancer. [2021]

9. China 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. [2022]

10. Germany 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. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Trastuzumab retreatment after relapse on adjuvant trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer: final results of the Retreatment after HErceptin Adjuvant trial. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Trastuzumab. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer. [2018]

14. United States pubmed.ncbi.nlm.nih.gov

Maximizing clinical benefit with trastuzumab. [2019]