Breast CancerPhase 1NCT04762901
LCI-BRE-MTN-NIR-001:Ph I Study of Niraparib in Combo With Standard Chemo in Metastatic Trip Neg Breast Cancer
A Phase 1 study testing Niraparib, Doxorubicin and Cyclophosphamide in people with Breast Cancer, run by Wake Forest University Health Sciences.
Trial summary
This is an open-label, two-stage, multi-arm Phase 1 study designed to evaluate the safety and preliminary efficacy of combining niraparib with four standard chemotherapy regimens used to treat TNBC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Niraparib, Doxorubicin and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2021to Jan 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Able to understand and willing to provide written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Male or female and age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0, 1 or 2 (Stage 1), or 0-1 (Stage 2) within 14 days prior to day 1 of treatment.
- Histologically or cytologically confirmed hormone receptor negative tumor (estrogen and progesterone) on pathology immunohistochemistry (IHC) assessment defined as <10% staining and HER2-negative, non-overexpressing defined by an IHC 0 or 1+ or fluorescence in-situ hybridization (FISH) HER2:CEP17 ratio < 2.0 with an average HER2 gene copy number of <4 signals/nucleus, and:
- Stage 1 (metastatic):
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- Measurable (by RECIST v1.1) or evaluable lesions
- Stage 2 (non-metastatic, treatment naïve, with no prior excisional biopsy/lumpectomy/LND staging):
- Primary tumor size ≥ 2 cm by at least one radiographic or clinical measurement. NOTE: this requirement does not apply to subjects with inflammatory TNBC.
- Clinical stage at presentation: cT1c-cT4, cN0-cN3
- Tumor tissue:
- Stage 1:
- Willing to provide tumor tissue for research purposes. Fresh biopsy of metastatic lesion prior to day 1 of treatment preferred if feasible. If fresh biopsy of metastatic lesion is not feasible, fresh biopsy can be obtained from the primary tumor site (i.e. breast). Tumor tissue from bone metastases is not acceptable. If fresh biopsy from metastatic tumor or primary tumor site is not possible, archival tumor tissue (formalin-fixed paraffin embedded [FFPE] or tumor block) may be used as long as it is from within 12 months of study entry. NOTE: If tissue is not available within required timeframe (i.e., either fresh or archival) subject will still be eligible for trial.
- Stage 2:
- Willing to undergo fresh biopsy of the primary tumor prior to day 1 of treatment for research purposes (breast is preferred; lymph node is acceptable). If not clinically feasible, then provide archived tumor tissue (FFPE or tumor block) of the primary tumor within 12 months of study entry. If archived tissue will be submitted rather than fresh biopsy, the archived tissue must be assessed and documented by pathology to ensure adequate tumor is present for correlative analysis. NOTE: For subjects who do not have archival tumor tissue available within required timeframe or if archival tissue insufficient, a pre-treatment core biopsy of the primary breast tumor must be obtained. If subjects have inflammatory breast cancer and a core biopsy is not possible, consideration can be given to obtain a skin punch biopsy.
- Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 14 days prior to day 1 of treatment.
- Absolute Neutrophil Count (ANC): greater than or equal to 1,000/µL
- Platelet Count greater than or equal to 100,000/µL without platelet transfusion within 4 weeks of day 1 of treatment
- Hemoglobin (Hgb): greater than or equal to 9 g/dL without red blood cell transfusion within 4 weeks of day 1 of treatment
- Serum creatinine (SCr): less than or equal to 1.5 × upper limit of normal (ULN)
- For subjects anticipated to receive anthracyclines, adequate cardiac function as defined by ≥50% Left Ventricular Ejection Fraction (LVEF) by ECHO or MUGA within 28 days prior to day 1 of treatment.
- Females of childbearing potential (FCBP) must have a negative serum pregnancy test within 7 days prior to day 1 of treatment and documented. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or are postmenopausal (>45 years of age and at least 12 consecutive months with no menses without an alternative medical cause).
- FCBP must be willing to use a highly effective contraceptive method (i.e., highly effective achieves a failure rate of <1% per year when used consistently and correctly) or a combination method from the time of informed consent until 30 days after treatment discontinuation. Contraceptive methods with low user dependency are preferable but not required.
- Acceptable methods of contraception (highly effective) are:
- Single method (one of the following is acceptable):
- Non-hormonal Intrauterine device (IUD)
- Vasectomy of a female subject's partner
- Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.
- Combination method (requires use of two of the following):
- Diaphragm with spermicide (Cannot be used in conjunction with cervical cap/spermicide)
- Cervical cap with spermicide (nulliparous women only)
- Contraceptive sponge with spermicide (nulliparous women only)
- Male condom or female condom (cannot be used together) with spermicide
- Male subjects with female partners who are of child-bearing potential, should use a highly effective method of contraception during niraparib therapy and for 90 days after receiving the last dose of niraparib.
- Subjects must agree to not donate blood for 90 days after receiving the last dose of niraparib.
- Female subjects must agree to not breastfeed during the study or for 30 days after the last dose of study treatment and male subjects must not donate sperm during niraparib therapy and for 90 days after receiving the last dose of niraparib.
- As determined by the enrolling physician, ability of the subject to understand and comply with study procedures for the entire length of the study.
- Ability to swallow oral medications.
- Stage 1 Exclusion Criteria
- Subjects meeting any of the criteria below may not participate in Stage 1 of the study:
- Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate if there is no evidence of disease progression for at least 4 weeks after CNS-directed treatment as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period, are asymptomatic, have no requirement for steroids, no requirement for anticonvulsants, and stable CNS radiographic study showing no significant vasogenic edema ≥ 4 weeks since completion of radiation and ≥ 1 week since discontinuation of steroids. Carcinomatous meningitis precludes a subject from study participation regardless of clinical stability.
- More than 3 prior lines of chemotherapy for triple-negative metastatic disease.
- Not recovered (i.e., ≥ Grade 1) from adverse events due to agents previously administered; NOTE: Subjects with ≤ Grade 2 neuropathy or alopecia of any grade are an exception.
- Prior chemotherapy within 3 weeks, prior targeted small molecule therapy or radiation therapy within 2 weeks, or prior anti-cancer monoclonal antibody for direct anti-neoplastic treatment within 3 weeks prior to day 1 of treatment.
- History or known allergic reaction to doxorubicin, cyclophosphamide, paclitaxel or carboplatin.
- For Arm 1, any prior anthracycline exposure.
- For Arm 2, prior doxorubicin exposure of > 300 mg/m2 or equivalent anthracycline exposure (i.e. epirubicin dose > 540 mg/m2).
- Stage 2 Exclusion Criteria
- Subjects meeting any of the criteria below may not participate in Stage 2 of the study:
- Final needle aspirate (FNA) alone to diagnose primary breast cancer.
- Excisional biopsy or lumpectomy performed prior to screening.
- Surgical axillary staging procedure prior to screening; NOTE: the following procedures are permitted prior to screening:
- FNA or core biopsy of an axillary node for any subject
- Although not recommended, a pre-neoadjuvant therapy sentinel node (SN) biopsy for subjects with clinically negative axillary nodes
- Definitive radiologic evidence of metastatic disease.
- History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral ductal carcinoma in-situ (DCIS) treated with radiotherapy (NOTE: subjects with a lobular CIS (LCIS) are eligible).
- Treatment including chemotherapy, radiation, and/or targeted therapy administered for the currently diagnosed breast cancer prior to screening.
- Previous therapy with anthracyclines for any malignancy.
- History of known allergic reaction to doxorubicin or cyclophosphamide.
- Overall Exclusion Criteria
- Subjects meeting any of the criteria below may not participate in the study:
- Active infection requiring systemic therapy (NOTE: at discretion of investigator, subjects with uncomplicated urinary tract infections may be eligible).
- Major surgery within 3 weeks of day 1 of treatment.
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Has had diagnosis, detection or treatment of another type of cancer ≤ 2 years prior to day 1 of treatment (exceptions include basal cell or squamous cell skin cancer, or in-situ cervical cancer that has been definitively treated).
- Known hypersensitivity to the components of niraparib or the excipients.
- Prior treatment with any PARP inhibitor.
- Has received any other investigational agents within 4 weeks of day 1 of treatment or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to day 1 of treatment.
- Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS).
- Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Poor medical risk as evidenced by uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders or psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator.
- Received a transfusion (platelets or red blood cells) ≤ 4 weeks of day 1 of treatment.
- Subject has a condition (such as transfusion dependent anemia or thrombocytopenia) that might confound the results of the study or interfere with the subject's participation for the full duration of the study treatment or that makes it not in the best interest of the subject to participate.
Who cannot join
None listed.
About this study
Official title: LCI-BRE-MTN-NIR-001: A Phase I Study of Niraparib in Combination With Standard Chemotherapy in Metastatic Triple-Negative Breast Cancer
This is an open-label, two-stage, multi-arm Phase 1 study designed to evaluate the safety and preliminary efficacy of combining niraparib with four standard chemotherapy regimens used to treat TNBC.
Read the detailed description
Niraparib is an oral, selective poly ADP ribose polymerase (PARP)-1 and PARP-2 inhibitor. A strategy of combining a PARP inhibitor, as a chemopotentiator, with chemotherapy is a promising approach in the treatment of triple-negative breast cancer. This study will evaluate the combination of niraparib with several standard chemotherapy regimens used to treat breast cancer to determine a recommended Stage 2 dose (RS2D) of chemotherapy regimens with niraparib. Stage 1 will be conducted in subjects with metastatic TNBC and will include 4 chemotherapy treatment arms in escalating dose levels (Arm 1: doxorubicin + cyclophosphamide (AC) every 14 days with pegfilgrastim (or biosimilar) for 4 cycles followed by AC every 21 days; Arm 2: AC every 21 days; Arm 3: weekly paclitaxel; Arm 4: weekly paclitaxel + carboplatin every 21 days), each combined with oral daily niraparib. Treatment will continue until disease progression, unacceptable toxicity, or subject withdrawal.Stage 2 will be conducted in subjects with non-metastatic TNBC. Subjects will receive neoadjuvant chemotherapy with either AC every 14 days (Arm 1A) or every 21 days (Arm 2A) at the RS2D of chemotherapy combined with oral daily niraparib from Stage 1. Treatment will continue for 4 cycles.
- Conditions
- Breast Cancer
- Being tested
- Niraparib, Doxorubicin, Cyclophosphamide, Paclitaxel, Pegfilgrastim
- Keywords
- Triple-negative
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called ZEJULA
Oral tablet
DoxorubicinDrug
IV
CyclophosphamideDrug
IV
PaclitaxelDrug
IV
PegfilgrastimDrug
Injection
CarboplatinDrug
IV
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 Arm 1 | Experimental | Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles, followed by AC IV every 21 days Receives: Drug: Niraparib; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Pegfilgrastim |
| Stage 1 Arm 2 | Experimental | Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days Receives: Drug: Niraparib; Drug: Doxorubicin; Drug: Cyclophosphamide |
| Stage 1 Arm 3 | Experimental | Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, 15, and 22 every 28 days Receives: Drug: Niraparib; Drug: Paclitaxel |
| Stage 1 Arm 4 | Experimental | Niraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, and 15 every 21 days and carboplatin IV every 21 days Receives: Drug: Niraparib; Drug: Paclitaxel; Drug: Carboplatin |
| Stage 2 Arm 1 | Experimental | Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles Receives: Drug: Niraparib; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Pegfilgrastim |
| Stage 2 Arm 2 | Experimental | Niraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days Receives: Drug: Niraparib; Drug: Doxorubicin; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1 - Evaluate dose-limiting toxicities (DLT) separately for Arms 1, 2, 3, and 4 and establish recommended Stage 2 dose of chemotherapy in combination with niraparib
The DLT variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined DLT.
Measured: up to 28 days
Stage 2 - Assess clinically significant toxicities separately for Arms 1 and 2 after RS2D of niraparib is determined.
The clinically significant toxicity variable will be determined for each subject as a binary variable indicating whether or not the subject experienced a niraparib-related dose delay of at least 28 days or a Grade 3 or higher niraparib-related non-hematologic toxicity.
Measured: up to 84 days
Secondary outcomes (22)
Stage 1 - Objective response rate (ORR)
Objective response will be determined for each subject in Stage 1 as a binary variable indicating whether or not the subject achieved a best overall response of CR or PR
Measured: up to 30 days post-treatment discontinuation
Stage 1 - Duration of response (DoR)
Duration of Response (DoR) will be determined for subjects in Stage 1 who experience a PR or better and is defined as the duration of time from the first assessment that determined a CR or PR to the date of the first occurrence of progressive disease or death.
Measured: up to 5 years post-treatment discontinuation
Stage 1 - Clinical benefit rate (CBR)
Clinical benefit will be determined for each subject in Stage 1 as a binary variable indicating whether or not the subject achieved a best overall response of CR, PR, or SD
Measured: up to 30 days post-treatment discontinuation
Stage 1 - Progression free survival (PFS)
PFS will be determined for all subjects in Stage 1 and is defined as the duration of time from enrollment to the first occurrence of either progressive disease or death.
Measured: up to 5 years post-treatment discontinuation
Stage 1 - Overall survival (OS)
Overall survival is defined as the duration of time from enrollment to the date of death from any cause.
Measured: up to 5 years post-treatment discontinuation
Stage 1 - Cumulative incidence of secondary malignancies including MDS
Secondary malignancies (including MDS) will be defined as a time to event endpoint and will be calculated from the date of enrollment.
Measured: up to 5 years post-treatment discontinuation
Stage 1 - Overall safety profile - Adverse Events of Special Interest (AESIs)
The AESI variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined AESI.
Measured: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Adverse Events (AEs)
The AE variable will be determined for each subject as a binary variability indicating whether or not subject experienced an AE per CTCAE V5.0.
Measured: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Death on Study Therapy
The death of study therapy variable will be determined for each subject as a binary variability indicating whether or not subject experienced a Grade 5 event.
Measured: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Complete Blood Count with Differential (CBCD)
The CBCD variable will be collected quantitatively for each subject.
Measured: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Comprehensive Metabolic Profile (CMP)
The CMP variable will be collected quantitatively for each subject.
Measured: up to 30 days post-treatment discontinuation
Stage 2 - Pathologic complete response (pCR)
Pathologic complete response (pCR) will be determined for each subject in Stage 2 as a binary variable indicating whether the subject experiences a pCR to neoadjuvant therapy.
Measured: up to 4 weeks post-surgery
Stage 2 - Clinical complete response (cCR)
Clinical complete response (cCR) will be determined for each subject in Stage 2 as a binary variable indicating whether the subject experiences a cCR to neoadjuvant therapy.
Measured: up to 4 weeks post-surgery
Stage 2 - Relapse-free survival
RFS will be determined for all subjects in Stage 2 and is defined as the duration of time from enrollment to the first occurrence of either disease progression prior to surgery, disease relapse after surgery, or death.
Measured: up to 5 years post-treatment discontinuation
Stage 2 - Overall survival
Overall survival is defined as the duration of time from enrollment to the date of death from any cause.
Measured: up to 5 years post-treatment discontinuation
Stage 2 - Cumulative incidence of secondary malignancies including MDS
Secondary malignancies (including MDS) will be defined as a time to event endpoint and will be calculated from the date of enrollment.
Measured: up to 5 years post-treatment discontinuation
Stage 2 - Overall safety profile - Adverse Events of Special Interest (AESIs)
The AESI variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined AESI.
Measured: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Adverse Events (AEs)
The AE variable will be determined for each subject as a binary variability indicating whether or not subject experienced an AE per CTCAE V5.0.
Measured: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Serious Adverse Events (SAEs)
The SAE variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined SAE.
Measured: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Death on Study Therapy
The death of study therapy variable will be determined for each subject as a binary variability indicating whether or not subject experienced a Grade 5 event.
Measured: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Complete Blood Count with Differential (CBCD)
The CBCD variable will be collected quantitatively for each subject.
Measured: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Comprehensive Metabolic Profile (CMP)
The CMP variable will be collected quantitatively for each subject.
Measured: up to 4 weeks post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start1 Apr 2021 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionJan 2026 (estimated)
Why it stopped: Funding was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Tesaro, Inc.
- Responsible party
- Sponsor
- Investigators
- Antoinette Tan, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04762901
- Sponsor's protocol ID
- LCI-BRE-MTN-NIR-001
- Other IDs
- 00048055
- Status last verified
- May 2021
- First submitted
- 17 Jan 2021
- Last updated
- 26 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LCI-BRE-MTN-NIR-001: A Phase I Study of Niraparib in Combination With Standard Chemotherapy in Metastatic Triple-Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT04762901
- Acronym / sponsor ID
- LCI-BRE-MTN-NIR-001
- Conditions
- Breast Cancer
- Keywords
- Triple-negative
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding was terminated.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Tesaro, Inc.
- Study start
- 1 Apr 2021 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 21 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, two-stage, multi-arm Phase 1 study designed to evaluate the safety and preliminary efficacy of combining niraparib with four standard chemotherapy regimens used to treat TNBC.
Detailed description
Niraparib is an oral, selective poly ADP ribose polymerase (PARP)-1 and PARP-2 inhibitor. A strategy of combining a PARP inhibitor, as a chemopotentiator, with chemotherapy is a promising approach in the treatment of triple-negative breast cancer. This study will evaluate the combination of niraparib with several standard chemotherapy regimens used to treat breast cancer to determine a recommended Stage 2 dose (RS2D) of chemotherapy regimens with niraparib. Stage 1 will be conducted in subjects with metastatic TNBC and will include 4 chemotherapy treatment arms in escalating dose levels (Arm 1: doxorubicin + cyclophosphamide (AC) every 14 days with pegfilgrastim (or biosimilar) for 4 cycles followed by AC every 21 days; Arm 2: AC every 21 days; Arm 3: weekly paclitaxel; Arm 4: weekly paclitaxel + carboplatin every 21 days), each combined with oral daily niraparib. Treatment will continue until disease progression, unacceptable toxicity, or subject withdrawal.Stage 2 will be conducted in subjects with non-metastatic TNBC. Subjects will receive neoadjuvant chemotherapy with either AC every 14 days (Arm 1A) or every 21 days (Arm 2A) at the RS2D of chemotherapy combined with oral daily niraparib from Stage 1. Treatment will continue for 4 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Stage 1 Arm 1 | Experimental | Drug: Niraparib, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: PegfilgrastimNiraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles, followed by AC IV every 21 days |
| Stage 1 Arm 2 | Experimental | Drug: Niraparib, Drug: Doxorubicin, Drug: CyclophosphamideNiraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days |
| Stage 1 Arm 3 | Experimental | Drug: Niraparib, Drug: PaclitaxelNiraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, 15, and 22 every 28 days |
| Stage 1 Arm 4 | Experimental | Drug: Niraparib, Drug: Paclitaxel, Drug: CarboplatinNiraparib 100 mg orally once daily, Paclitaxel IV Days 1, 8, and 15 every 21 days and carboplatin IV every 21 days |
| Stage 2 Arm 1 | Experimental | Drug: Niraparib, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: PegfilgrastimNiraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 14 days with pegfilgrastim (or biosimilar) for 4 cycles |
| Stage 2 Arm 2 | Experimental | Drug: Niraparib, Drug: Doxorubicin, Drug: CyclophosphamideNiraparib 100 mg orally once daily, Doxorubicin and Cyclophosphamide (AC) IV every 21 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (73 listed)
- Subject must meet all of the following applicable inclusion criteria to participate in this study:
- Able to understand and willing to provide written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Male or female and age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0, 1 or 2 (Stage 1), or 0-1 (Stage 2) within 14 days prior to day 1 of treatment.
- Histologically or cytologically confirmed hormone receptor negative tumor (estrogen and progesterone) on pathology immunohistochemistry (IHC) assessment defined as <10% staining and HER2-negative, non-overexpressing defined by an IHC 0 or 1+ or fluorescence in-situ hybridization (FISH) HER2:CEP17 ratio < 2.0 with an average HER2 gene copy number of <4 signals/nucleus, and:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZEJULAOral tablet | Drug | Stage 1 Arm 1, Stage 1 Arm 2, Stage 1 Arm 3, Stage 1 Arm 4, Stage 2 Arm 1, Stage 2 Arm 2 |
| DoxorubicinIV | Drug | Stage 1 Arm 1, Stage 1 Arm 2, Stage 2 Arm 1, Stage 2 Arm 2 |
| CyclophosphamideIV | Drug | Stage 1 Arm 1, Stage 1 Arm 2, Stage 2 Arm 1, Stage 2 Arm 2 |
| PaclitaxelIV | Drug | Stage 1 Arm 3, Stage 1 Arm 4 |
| PegfilgrastimInjection | Drug | Stage 1 Arm 1, Stage 2 Arm 1 |
| CarboplatinIV | Drug | Stage 1 Arm 4 |
Primary outcome
Stage 1 - Evaluate dose-limiting toxicities (DLT) separately for Arms 1, 2, 3, and 4 and establish recommended Stage 2 dose of chemotherapy in combination with niraparib
Time frame: up to 28 days
The DLT variable will be determined for each subject as a binary variability indicating whether or not subject experienced a protocol-defined DLT.
Stage 2 - Assess clinically significant toxicities separately for Arms 1 and 2 after RS2D of niraparib is determined.
Time frame: up to 84 days
The clinically significant toxicity variable will be determined for each subject as a binary variable indicating whether or not the subject experienced a niraparib-related dose delay of at least 28 days or a Grade 3 or higher niraparib-related non-hematologic toxicity.
22 secondary outcomes
Stage 1 - Objective response rate (ORR)
Time frame: up to 30 days post-treatment discontinuation
Stage 1 - Duration of response (DoR)
Time frame: up to 5 years post-treatment discontinuation
Stage 1 - Clinical benefit rate (CBR)
Time frame: up to 30 days post-treatment discontinuation
Stage 1 - Progression free survival (PFS)
Time frame: up to 5 years post-treatment discontinuation
Stage 1 - Overall survival (OS)
Time frame: up to 5 years post-treatment discontinuation
Stage 1 - Cumulative incidence of secondary malignancies including MDS
Time frame: up to 5 years post-treatment discontinuation
Stage 1 - Overall safety profile - Adverse Events of Special Interest (AESIs)
Time frame: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Adverse Events (AEs)
Time frame: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Death on Study Therapy
Time frame: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Complete Blood Count with Differential (CBCD)
Time frame: up to 30 days post-treatment discontinuation
Stage 1 - Overall safety profile - Comprehensive Metabolic Profile (CMP)
Time frame: up to 30 days post-treatment discontinuation
Stage 2 - Pathologic complete response (pCR)
Time frame: up to 4 weeks post-surgery
Stage 2 - Clinical complete response (cCR)
Time frame: up to 4 weeks post-surgery
Stage 2 - Relapse-free survival
Time frame: up to 5 years post-treatment discontinuation
Stage 2 - Overall survival
Time frame: up to 5 years post-treatment discontinuation
Stage 2 - Cumulative incidence of secondary malignancies including MDS
Time frame: up to 5 years post-treatment discontinuation
Stage 2 - Overall safety profile - Adverse Events of Special Interest (AESIs)
Time frame: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Adverse Events (AEs)
Time frame: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Serious Adverse Events (SAEs)
Time frame: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Death on Study Therapy
Time frame: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Complete Blood Count with Differential (CBCD)
Time frame: up to 4 weeks post-surgery
Stage 2 - Overall safety profile - Comprehensive Metabolic Profile (CMP)
Time frame: up to 4 weeks post-surgery
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoinette Tan, MD principal investigator
Wake Forest University Health Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Niraparib, Doxorubicin and Cyclophosphamide in people with Breast Cancer, run by Wake Forest University Health Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 73 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1 - Evaluate dose-limiting toxicities (DLT) separately for Arms 1, 2, 3, and 4 and establish recommended Stage 2 dose of chemotherapy in combination with niraparib (time frame: up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2022.