An Open-Label, Randomized-Sequence, Multicenter, Single-Crossover Study to Assess the Relative Bioavailability of Niraparib Tablet Formulation Compared to Niraparib Capsule Formulation in Patients With Advanced Solid Tumors

Trial Purpose and Description

Primary Outcome Measures  :

  1. Stage 1: Intrasubject variability of niraparib AUC [ Time Frame: Approximately 1 year ]
  2. Stage 1: Intrasubject variability of niraparib Cmax [ Time Frame: Approximately 1 year ]
  3. Stage 1 & Stage 2: Relative bioavailability (BA) of 300 mg niraparib administered as a tablet (1 × 300 mg) formulation versus capsule (3 × 100 mg) formulation [ Time Frame: Approximately 1 year ]

Secondary Outcome Measures  :

  1. The number of participants with treatment emergent adverse events (TEAEs) according to NCI CTCAE v4.03 [ Time Frame: Approximately 1 year ]
  2. AUC of a metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
  3. Cmax of a metabolite of niraparib (M1) when administered as a tablet or capsule formulation in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]



Eligibility Criteria

Main criteria for inclusion:

PK Phase:

To be considered eligible to participate in this study, all of the following requirements must be met:

  • Patients with histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumors that have failed to respond to standard therapy, has progressed despite standard therapy, or for which no standard therapy exists, and who may benefit from treatment with a PARP inhibitor as assessed by the Investigator.
  • ECOG performance status of 0 to 2.
  • Adequate organ function as defined below:
    • Absolute neutrophil count ≥ 1,500/μL
    • Platelets ≥ 100,000/μL
    • Hemoglobin ≥ 9 g/dL (5.6 mM)
    • Serum creatinine ≤ 1.5 × the upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation or 24-hour urine creatinine clearance.
    • Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN unless liver metastases are present, in which case, they must be ≤ 5 × ULN
  • Patient has recovered to Grade 1 toxicity from prior cancer therapy (a patient with Grade 2 neuropathy or Grade 2 alopecia is an exception to this criterion and may qualify for this study).
  • Female Patient of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug,
  • Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study drug through 90 days after the last dose of study drug

Key Exclusion, PK Phase:

  • Known diagnosis of immunodeficiency
  • Symptomatic uncontrolled brain or leptomeningeal metastases.
  • Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
  • Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder; nonmalignant systemic disease; or active, uncontrolled infection.
  • Known history of myelodysplastic syndrome or acute myeloid leukemia.
  • Patient is currently receiving a sensitive cytochrome P450 (CYP) 1A2 substrates with a narrow therapeutic index (e.g., tizanidine and theophylline) (Does not apply for Extension Phase).
  • Patient is currently taking any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor, and verapamil (Does not apply for Extension Phase).
  • Patient taking proton pump inhibitors, antacids, or histamine 2 blockers within 48 hours prior to study drug administration, and/or within 6 hours after study drug administration (Does not apply for Extension Phase).
  • Patient has gastric, gastro-esophageal or esophageal cancer; patient is unable to swallow orally administered medication; or patient has gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of niraparib.
  • Patient has known active hepatic disease
  • Patient has a past or current history of chronic alcohol use.
  • Patient has significant pleural effusion or ascites that is expected to require drainage during the PK Phase (Does not apply for Extension Phase).

Key Inclusion, Extension Phase:

  • ECOG performance status of 0 to 2.
  • Adequate organ function as defined below
    • Absolute neutrophil count ≥ 1,500/μL
    • Platelets ≥ 100,000/μL
    • Hemoglobin ≥ 9 g/dL (5.6 mM)
    • Serum creatinine ≤ 1.5 × the ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation or 24-hour urine creatinine clearance
    • Total bilirubin ≤ 1.5 × ULN except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 × ULN of the direct bilirubin.
    • AST and ALT ≤ 2.5 × ULN unless liver metastases are present, in which case, they must be ≤5 × ULN
  • Female patient of childbearing potential is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from Screening through 180 days after the last dose of study drug.
  • Male patient agrees to use an adequate method of contraception and not donate sperm starting with the first dose of study drug through 90 days after the last dose of study drug.

TESARO, Inc

Start Date: 01/30/2019

End Date: 05/31/2019

Last Updated: 01/31/2019

Study HIC#: 2000024073