LCI-BRE-MTN-NIR-001:Ph I Study of Niraparib in Combo With Standard Chemo in Metastatic Trip Neg Breast Cancer

NCT04762901 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: LCI-BRE-MTN-NIR-00100048055
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Breast Cancer

Keywords

Triple-negative

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  up to 84 days

Secondary Outcomes (22)

• Stage 1 - Objective response rate (ORR)

  up to 30 days post-treatment discontinuation

• Stage 1 - Duration of response (DoR)

  up to 5 years post-treatment discontinuation

• Stage 1 - Clinical benefit rate (CBR)

  up to 30 days post-treatment discontinuation

• Stage 1 - Progression free survival (PFS)

  up to 5 years post-treatment discontinuation

• Stage 1 - Overall survival (OS)

  up to 5 years post-treatment discontinuation

Study Arms (6)

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

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

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

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

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

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

Drug: Niraparib; Drug: Doxorubicin; Drug: Cyclophosphamide

Interventions

Niraparib DRUG

Oral tablet

Also known as: ZEJULA

Stage 1 Arm 1; Stage 1 Arm 2; Stage 1 Arm 3; Stage 1 Arm 4; Stage 2 Arm 1; Stage 2 Arm 2

Doxorubicin DRUG

IV

Stage 1 Arm 1; Stage 1 Arm 2; Stage 2 Arm 1; Stage 2 Arm 2

Cyclophosphamide DRUG

IV

Stage 1 Arm 1; Stage 1 Arm 2; Stage 2 Arm 1; Stage 2 Arm 2

Paclitaxel DRUG

IV

Stage 1 Arm 3; Stage 1 Arm 4

Pegfilgrastim DRUG

Injection

Stage 1 Arm 1; Stage 2 Arm 1

Carboplatin DRUG

IV

Stage 1 Arm 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• a. 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Tesaro, Inc.: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Interventions

niraparib; Doxorubicin; Cyclophosphamide; Paclitaxel; pegfilgrastim; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Antoinette Tan, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2021
• First Posted: February 21, 2021
• Study Start: April 1, 2021
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: April 26, 2022

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share