An investigator-initiated phase II trial of IMmune checkpoint inhibitor And niraparib for patients with homologous recombination repair GENE-mutated unresectable/recurrent advanced solid tumor

JRCT ID: jRCT2051210120

Registered date:09/11/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Urothelial cancer, renal cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma
• Date of first enrollment: 22/04/2022
• Target sample size: 57
• Study type: Interventional

Intervention(s)

Investigational drug
Niraparib: 200 mg/body or 300 mg/body (body weight and neutrophil count greater than or equal to specified values), once daily

Concomitant use of PD-1 inhibitors
(Renal cancer, gastric cancer, esophageal cancer, head and neck cancer, malignant melanoma)
Nivolumab: 240 mg/body, IV every 2 weeks
(Urothelial cancer)
Pembrolizumab: 240 mg/body, IV every 3 weeks.

Continue administration unless protocol treatment discontinuation criteria are met.

Outcome(s)

• Primary Outcome: Objective response rate (ORR) confirmed by site-investigator

Secondary Outcome

1)Progression-free survival: PFS
2)Overall survival: OS
3)Disease control rate: DCR
4)Duration of response: DoR
5)Time to treatment failure: TTF
6)Changes of sum of tumor diameter
7)ORR in patients with HRR gene mutations on ctDNA testing
8)ORR, DCR, PFS and OS in patients with HRR gene mutation on ctDNA testing in each of germline and somatic cell mutations
9)Rate of adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Malignant progression after one or more standard therapy by PD-1/PD-L1 inhibitors, and completion of standard therapy in principle
2) Diagnosed with the target disease (Unresectable advanced or recurrent urothelial cancer, renal cancer, gastric cancer, esophageal cancer, head and neck cancer, malignant melanoma) with HRR gene mutation in the germline or somatic cells which were detected by the specified tests
3) Measurable lesions
4) Participating in or planning to participate in MONSTAR-SCREEN-2 study
5) Legal adult on informed consent
6) ECOG PS: 0 or 1
7) Appropriate physical function confirmed by laboratory values within 14 days before enrollment
8) (Female of childbearing potential) Agreed to contraception and not to donate oocytes from the consent to 180 days after the last dose of Niraparib
9) (Male) Agreed to contraception from the start of study treatment to 180 days after the last dose of Niraparib, and agreed not to donate sperms from the start of study treatment to 90 days after the last dose of Niraparib or 120 days after the last dose of a PD-1 inhibitor, whichever is later.
10) Written consent to participate in the clinical trial

Exclude criteria

1) Active double and more cancer
2) History of treatment with PARP inhibitors
3) Moderate or severe ascites observed by CT or MRI performed within 28 days prior to the enrollment
4) Diagnosed with carcinomatous meningitis, symptomatic brain metastases, or spinal metastases requiring surgical intervention at the enrollment,
5) Received systemic steroid therapy (10 mg/day or more dose equivalent to prednisolone) or immunosuppressants within 14 days before enrollment
6) Received any cytotoxic anticancer drugs, molecular-targeted drugs or antibodies for aimed at treating cancer within a certain period of time before enrollment
7) Performed surgery with systemic anesthesia within 21 days before enrollment, or unrecovered fully from the complications of the surgery
8) Performed radiation therapy within 14 days before enrollment, or requiring corticosteroids (10 mg/day or more dose equivalent to prednisolone) without recovery from radiation therapy-related toxicity
9) Historic or coexisting symptomatic congestive heart failure (NYHA Classes 2-4) within 6 months before enrollment, or arrhythmia requiring treatment
10) Historic or coexisting myocardial infarction or unstable angina within 6 months before enrollment
11) Uncontrolled hypertension at the enrollment
12) Lymphatic malignancy at the enrollment.
13) History of myelodysplastic syndrome or acute myeloid leukemia
14) History of bone marrow transplantation or organ transplantation
15) Historic or coexisting noninfectious interstitial lung disease or pneumonitis requiring steroid therapy at the enrollment
16) Active autoimmune disease requiring systemic therapy within 2 years before enrollment
17) Received live vaccines within 30 days before the scheduled start of protocol treatment
18) Infections requiring intravenous antibiotics, antivirals or antifungals at the enrollment
19) Active hepatitis B at the enrollment
20) Positive HIV antibody, HTLV -1 antibody or HCV antibody at the enrollment
21) Unrecovered adverse events to Grade 1 or less
22) Serious hypersensitivity to components of drugs used in protocol therapy identified at the enrollment
23) Rare genetic disorders of lactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorption
24) (Female) Pregnant (including suspected pregnancy) or breastfeeding
25) Psychosis or psychiatric symptoms judged as difficult to participate in the study by the investigator
26) Permanently discontinuation of PD-1/PD-L1 inhibitors in the prior therapy due to immune-mediated adverse events

Related Information

• Primary Sponsor: Kato Taigo
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development
• Secondary ID(s): Nil known