Solid Tumor with chromothripsis
Conditions
Interventions
Nivolumab + Niraparib therapy
The following courses of chemotherapy are administered as a 4-week / 1 course until progressive disease (PD) or for 1 year after the start of study treatment.
- Nivoluma
Sponsors
Kenmotsu Hirotsugu
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Pathologically diagnosed solid tumor (carcinoma for which nivolumab is indicated at the time of enrollment). 2) Chromothripsis has been detected in whole genome analysis using tumor tissue specimens. 3) Pathogenic mutations in homologous recombination repair-related genes have been detected. 4) Prior administration of PD-1/PD-L1 inhibitors. 5) The age of 18 or older. 6) ECOG Performance Status of 0 or 1. 7) Have at least one measurable lesion evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, excluding previously irradiated lesions. 8) Adequate organ function is maintained, and laboratory data within 14 days prior to enrollment meet the following criteria (1) Neutrophil count >-1500/mm3 (2) Platelet count >-10.0*104/mm3 (3) Hemoglobin >-8.0/dL (4) Total bilirubin -92% 9) Expected survival of at least 12 weeks from the date of enrollment. 10) No diarrhea or intestinal obstruction. Participants must be able to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the formulation. Participants must not have any gastrointestinal disease that would interfere with the absorption of oral olaparib. 11) Participants must not have Grade 3 or higher adverse events causally related to PD-1 pathway inhibitors at the time of enrollment. However, participants with a history of Grade 3 or higher adverse events causally related to PD-1 pathway inhibitors prior to enrollment are eligible if the adverse events have resolved to Grade 1 or lower with steroid therapy equivalent to <-10 mg/day of prednisolone. Participants who have received immunosuppressive agents other than steroids or immunoglobulin therapy are ineligible. 12) No evidence of active interstitial lung disease at the time of enrollment. Participants with a history of interstitial pneumonia due to chemotherapy or radiotherapy may be enrolled if steroid therapy has been discontinued and the patient has recovered.. 13) Participants must not have a history of concomitant autoimmune disease or chronic or recurrent autoimmune disease. However, participants with well-controlled type 1 diabetes mellitus, hyperthyroidism/hypothyroidism requiring only hormone replacement therapy, or autoimmune dermatoses (such as pemphigus, psoriasis vulgaris, bullous pemphigoid, or vitiligo) that do not require systemic treatment are eligible. 14) If the participant is of reproductive potential, they must agree to use an appropriate contraceptive method (hormonal or barrier method) during the study and for at least 16 weeks after the last dose of study treatment. If the participant is a female of childbearing potential, serum or urine pregnancy test results must be negative within 7 days prior to enrollment. If the subject is a female of childbearing potential, the results of serum or urine pregnancy tests must be negative within 7 days prior to enrollment. 15) Written informed consent must be obtained from the subject before participation in the study.
Exclusion criteria
Exclusion criteria: 1) Participants with symptomatic brain metastases. However, participants may be eligible if their symptoms are controlled with local therapy and at least 14 days have passed since cranial irradiation (whole-brain radiation, primary lesion radiation, or stereotactic radiation) and the discontinuation of associated steroid therapy, or at least 28 days have passed since surgical resection. Participants with spinal cord compression are ineligible unless they have received appropriate treatment and have been clinically stable for at least 28 days. 2) Prior treatment with PARP inhibitors, including niraparib. 3) History of bone marrow transplantation. 4) Resting electrocardiograms (ECGs) showing two or more measurements of QTc >470 msec within 24 hours, or a family history of long QT syndrome. 5) Participants with severe, uncontrolled medical conditions, including but not limited to uncontrolled ventricular arrhythmias, myocardial infarction within the past 3 months, uncontrolled seizures, unstable spinal cord compression, or superior vena cava syndrome. 6) Participants who have not completed the required washout period before enrollment: - Surgical therapy: 28 days (14 days for minor invasive procedures such as colostomy placement; 7 days for subcutaneous venous access device placement). - Radiation therapy: 28 days (14 days for palliative irradiation of bone metastases, except for pelvic irradiation, or brain metastases). - Chemotherapy (including antibody drugs): 28 days (42 days for nitrosourea agents and mitomycin C) - Hormonal therapy: 28 days - Pleurodesis: 14 days 7) Active infection requiring systemic treatment. 8) Fever >-38C at the time of enrollment. 9) Participants with New York Heart Association (NYHA) class II to IV congestive heart failure or symptomatic, uncontrolled arrhythmia. 10) Participants with unstable angina (onset or worsening within the past 3 weeks) or a history of myocardial infarction within the past 6 months. 11) Participants with cirrhosis classified as Child-Pugh class B or higher, or a history of hepatic encephalopathy associated with cirrhosis. 12) Participants requiring continuous systemic administration (oral or intravenous) of corticosteroids at a dose equivalent to >10 mg/day of prednisolone or receiving immunosuppressive agents. Participants receiving <-10 mg/day of prednisolone equivalent are eligible. However, those receiving other immunosuppressive agents (e.g., infliximab, cyclophosphamide, mycophenolate mofetil, cyclosporine, azathioprine, tacrolimus, tocilizumab) or systemic immunoglobulin therapy (oral or intravenous) are ineligible. 13) Unresolved toxicities from prior treatments exceeding Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of study drug initiation, except for alopecia, endocrine adverse events under hormone replacement therapy, and Grade 2 peripheral neuropathy. 14) Diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). 15) Participants enrolled in another clinical trial for an unapproved drug or medical device or involved in a scientific or medical study deemed incompatible with this trial. 16) History of severe hypersensitivity to nivolumab, niraparib, or their excipients. 17) Concomitant use of strong CYP3A4 inhibitors, including ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, and nelfinavir. 18) Immunocompromised individuals, including those who are serologically positive for human i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety | — |
Secondary
| Measure | Time frame |
|---|---|
| Response rate, Duration of response, Progression-free survival, Overall survival, Disease control rate | — |
Contacts
Public ContactSuguru Matsuda
Shizuoka Cancer Center
Outcome results
None listed