A Study of Niraparib in People With Soft Tissue Sarcoma Who Have Changes in Their Tumor DNA

Prior treatment

• Patient has had major surgery within 3 weeks prior to initiating protocol therapy. Note: patient must have recovered from any surgical effects.
• Uncontrolled intercurrent illness including current active or chronic infection requiring systemic therapy or the following cardiac criteria:
  • Symptomatic congestive heart failure (NYHA classification III or IV) within 6 months
  • Acute myocardial infarction ≤6 months prior to Day 1
  • Grade ≥2 ventricular arrhythmia ≤6 months prior to Day 1
  • History of cerebrovascular accident within 6 months before first dose of study drugs
• Prior therapy with a PARP inhibitor
• Patients who have not recovered from clinically significant adverse events of prior therapy to ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.
  • °If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy events due to a previously administered agent.
• Prior allogeneic stem cell transplantation or organ transplantation.
• Participant has received colony stimulating factors (e.g., granulocyte colonystimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
  • °If growth factors were used as neutropenic fever prophylaxis during a previous treatment regimen then enrollment is allowed, as long as 2 weeks as elapsed from the prior dose
• Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
• Participant has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[qualitative\] is detected).
  • Patients with chronic HBV infection with active disease who are on suppressive antiviral therapy prior to initiation of cancer therapy
  • Patients with HCV on treatment are eligible if HCV viral load is below the level of quantification

Other illness

• Participant has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of CNS hemorrhage.
  • Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.
• Known history of active Mycobacterium tuberculosis infection
• Presence of a gastrointestinal condition that may affect drug absorption
• Known allergy or reaction to any component of the study drug or its excipients.
• Participant has any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)

Lab values

• Participant has received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.

Other

• Patient is simultaneously enrolled on any therapeutic clinical trial.
• Women who are pregnant or breast feeding
• Patients expecting to have a child within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months after the last dose of study treatment(s) for women or 7 months for men.

• Age ≥ 18 years at the time of informed consent
• Participants or their legally authorized representatives (LARs) need to be willing to provide written informed consent/assent for the trial
• Be willing to comply with treatment protocol
• Histologically confirmed unresectable or metastatic soft tissue or uterine sarcoma
• Known deleterious or suspected deleterious alteration in at least one of the following prespecified DDR pathway genes:
  • Core Genes
  • Gene Pathway
  • BRCA1 FA/HR
  • BRCA2 FA/HR
  • BRIP1 FA/HR
  • BARD1 FA/HR
  • BLM FA/HR
  • PALB2 FA
  • MRE11 HR
  • NBN HR
  • RAD50 HR/NHEJ
  • RAD51B FA/HR
  • RAD51C HR
  • RAD51D HR
  • RAD52 HR
  • RAD54B HR
  • Other Genes
  • Gene Pathway
  • ABRAXAS1 NHEJ
  • ATM OTHER
  • ATR OTHER
  • CHEK1 OTHER
  • CHEK2 OTHER
  • ERCC4 NER
  • ERCC8 NER
  • FANCA FA
  • FANCC FA
  • FANCD2 FA
  • FANCE FA
  • FANCF FA
  • FANCG FA
  • FANCI FA
  • FANCL FA
  • FANCM FA/HR
  • MDC1 OTHER
  • PARP1 BER
  • RAD23B NER
  • RECQL4 HR
  • RPA1 NER
  • SLX4 FA/HR
  • XRCC2 FA/HR
  • XRCC4 NHEJ
  • XRCC6 NHEJ
  • A= Fanconi Anemia BER = Base Excision Repair NER = Nucleotide Excision Repair HR = Homologous Recombination NHEJ = Non-homologous End Joining
• Additional genes may be added to Appendix 18.1 in a study addendum as medical and scientific research and/or diagnostic testing evolves
• Alterations of uncertain significance must be approved for inclusion by the Principal Investigator
  • Performance status of ECOG ≤ 2
  • Progressed on at least 1 prior line of systemic therapy.
• Patients who decline standard of care first-line systemic therapy will be permitted to enroll
• Prior adjuvant therapy will not count if it was completed more than 1 year before the date of consent
  • Presence of measurable disease by RECIST 1.1
• Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
  • Adequate organ function determined within 14 days of treatment initiation, defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 K/mcL
• Platelets ≥ 100 K/ mcL
• Hemoglobin ≥ 9 g/dL
• Serum creatinine OR Measured or calculated creatinine clearance Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 . For calculated CrCL, the Cockcroft Gault formula or institutional standard formula can be used.
• Serum total bilirubin ≤1.5 X ULN OR ≤2 X ULN if hyperbilirubinemia is due to Gilbert's syndrome
• AST (SGOT) and ALT (SGPT) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); if liver metastases, then ≤ 5 × ULN
• International Normalized Ratio ≤1.5 X ULN (≤ 2.5 × ULN if on anticoagulants)
  • Women of childbearing potential must have a negative serum pregnancy test at screening and ≤ 72 hours prior to the first dose of study treatment.
  • Women of childbearing potential must be willing to use a highly effective method of contraception and not breastfeed for the duration of the study and for at least 6 months after the last dose of study medication
• Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Non-sterile male subjects and their female partners must be willing to use a highly effective method of contraception during the study treatment period and for at least 3 months after the last dose of study treatment. Nonsterile males must avoid sperm donation for the duration of the study and for at least 3 months after last study drug.
  • Prior chemotherapy or any investigational therapies or other anti-cancer agent must have been completed at least 4 weeks before the study drug administration. All AEs must be ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline. Patients who were treated with estrogen modulating therapies (aromatase inhibitors, tamoxifen, GnRH agonists etc.) must have been treated at least 2 weeks prior to study drug administration.
  • Radiation therapy encompassing \>20% of the bone marrow is prohibited within 2 weeks prior to Day 1 and during study treatment. Note: Palliative radiation therapy to a small field \>1 week prior to Day 1 of study treatment may be allowed.
  • Patients must have normal blood pressure or adequately treated and controlled hypertension. (i.e. systolic BP ≤ 140 mmHg and diastolic BP ≤ 90 mmHg) .
  • Patients receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.
  • Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with documented undetectable viral load and CD 4 count ≥350 within 6 months of the first dose of study treatment are eligible for this trial.