A phase II trial of niraparib for patients with BRCA-mutated gastrointestinal cancer

JRCT ID: jRCT2011200023

Registered date:01/03/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: biliary tract, pancreatic and other gastrointestinal cancer
• Date of first enrollment: 22/03/2021
• Target sample size: 60
• Study type: Interventional

Intervention(s)

For patients with body weight less than 77kg or having a platelet count less than 150,000 per mm3 prior to the first dose of drug, 200 mg of niraparib is orally administered once daily.
For patients with body weight of 77kg or more and a platelet count of 150,000 per mm3 or more prior to the first dose of drug, 300 mg of niraparib is orally administered once daily.

Outcome(s)

Primary Outcome

1) Objective response rate (ORR) determined by the judgment of the investigator or sub investigator in patients with BRCA mutation on genetic tests
2) ORR determined by the judgment of the investigator or sub investigator in patients with BRCA mutations on ctDNA test according to a screening study that utilizes comprehensive ctDNA sequencing (GOZILA study) conducted prior to the initiation of protocol treatment

Secondary Outcome

1) ORR determined by the judgment of central review
2) Progression-free survival (PFS) (assessed by the principal investigator or sub-investigator and central review)
3) Overall survival (OS)
4) Disease control rate (DCR)
5) Duration of response (DoR)
6) Time to treatment failure (TTF)
7) Change in tumor diameter sum
8) ORR, DCR, PFS, and OS by germline mutation (germline BRCA) and somatic mutation (somatic BRCA)
9) Incidence of adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Cancer diagnosed by histology or cytology and unresectable advanced/recurrent solid cancer (histology or cytology does not require confirmation at a registered institution if diagnosed at another hospital).
[Cohort A]
Biliary tract cancer patients with BRCA mutations refractory or intolerant to 1 or 2 prior regimens (histology includes adenocarcinoma and adenosquamous carcinoma only)
[Cohort B]
Pancreatic cancer patients with BRCA mutations refractory or intolerant to 1 or 2 prior regimens (histology includes adenocarcinoma and adenosquamous carcinoma only)
[Cohort C]
Patients with gastrointestinal and abdominal malignancies other than biliary tract cancer and pancreatic cancer who have BRCA mutations refractory to or intolerant to standard chemotherapy (prior treatment is based on the number of standard treatment regimens for each cancer type)
(If the patient received postoperative adjuvant chemotherapy and the period from the last dose of the chemotherapy to the confirmation date of recurrence is 24 weeks or more (including the same day of the 24th week), the chemotherapy received after confirmation of recurrence is regarded as the first regimen. The postoperative adjuvant chemotherapy is considered the first regimen if the period between the date of last dose of adjuvant chemotherapy and the date of confirmation of recurrence is less than 24 weeks.)
2) Genetic tests have confirmed germline or somatic BRCA mutations (likely pathogenic or pathogenic). This trial will be eligible if any of the following tests confirm that the patient has a BRCA mutation;
[Tests using ctDNA]
-Gene-panel testing with NGSs by Guardant360
-Gene-panel testing with NGSs by FoundationOne Liquid CDx
[Tests using tumor tissue samples]
-Gene-panel testing with insured NGSs.
-Gene-panel testing with a panel of clinical trial assay (CTA) developing at Hokkaido University Hospital
[Tests using blood genomic DNA]
-BRCA genetic testing by BRACAnalysis diagnostic system
-BRCA genetic testing conducted in the genetic medicine sector (e.g., genetic counselling, genetic medicine departments)
3) Measurable lesions by chest CT and abdomen-pelvis CT or abdomen-pelvis MRI
4) Age at enrollment date is 20 years or older
5) ECOG Performance status (PS) is 0 or 1 (the PS must be recorded in the medical record)
6) The most recent laboratory tests within 14 days before enrollment meets all of the following;
a. Neutrophils => 1,500 per mm3
b. Hemoglobin => 9.0 g/dL
c. Platelets => 10.0 x 10^4 per mm3
d. Total bilirubin <= 1.5 mg/dL
e. AST <= 100 IU/L
f. ALT <= 100 IU/L
g. Creatinine clearance* => 30 mL/min (*Cockcroft-Gault equation)
*The value estimated by the Cockcroft-Gault formula should be 30 mL/min/body or more. Even if the estimated value is less than 30 mL / min / body, it is eligible if it is more than 30 mL / min / body as measured by 24-hour urine collection.
Cockcroft-Gault equation: creatinine clearance value = (140-age) x body weight (kg)/ (72 x serum creatinine value) (for women, further multiply the obtained value by 0.85).
However, patients should not receive granulocyte colony-stimulating factors (including long acting [PEG]G-CSF) or blood transfusions within 14 days of testing.
7) Women who can be pregnant have consented to contraception for at least 6 months after the last dose of the investigational drug since obtaining informed consent. Men have agreed to contraception for at least 3 months after the last dose since the start of administration of the investigational drug.
8) Given written informed consent to participate in the study

Exclude criteria

1) Active double cancers: We do not exclude, a) completely resected basal cell carcinoma, carcinoma in situ, superficial bladder cancer, and squamous cell carcinoma of stage I; b) gastrointestinal cancers curatively resected by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR); c) other cancers without recurrence for more than 2 years.
2) Previously received PARP inhibitors
3) Abdominal-pelvic contrast CT or abdominal-pelvic contrast MRI showing moderate or greater ascites.
Moderate or greater ascites is defined as an ascites exceeding the pelvic cavity.
4) Patients who have cancerous meningitis, symptomatic brain metastases, and spinal metastases requiring surgical intervention at the time of enrollment
5) Systemic corticosteroid therapy (excluding temporary use for testing or prophylaxis) or immunosuppressive drugs, equivalent to prednisolone >10 mg/day, within 14 days before enrollment
6) Patients who have received anticancer drugs within 14 days before enrollment (e.g., chemotherapy) or other investigational drugs within 21 days before enrollment (e.g., chemotherapy, molecularly targeted therapy, immunotherapy)
7) Patients who have undergone surgery with general anesthesia within 28 days before enrollment
8) Patients who have received radiotherapy within 28 days before enrollment
However, in the case of palliative irradiation, patients who were irradiated before 14 days before enrollment will not be excluded.
9) History/complication of symptomatic congestive heart failure (New York Heart Association [NYHA]) class II-IV in the 6 months prior to enrollment or having arrhythmias (Grade 2 or higher) requiring treatment
10) Having a history/complication of myocardial infarction or unstable angina within 6 months prior to enrollment
11)Patients who have uncontrolled hypertension
12)Patients who have been diagnosed as a lymphoid malignancy
13)Patients who have a history of myelodysplastic syndrome or acute myeloid leukemia
14)Patients who have a history of bone marrow or organ transplantation
15) Patients who have a history or concomitant noninfectious interstitial lung disease or pneumonitis requiring treatment with steroids
16) Patients who have infections requiring intravenous antibiotics, antivirals, and antifungals
17) HBs antigen-negative, HBs antibody or HBc antibody-positive, and HBV-DNA-positive (not excluded if not sensitive even if antiviral drugs are used concomitantly)
18) Positive for either HIV antibody, HTLV-1 antibody, HBsAg, or HCV antibody (patients with positive HCV antibody but no detectable HCV-RNA will not be excluded)
19) Adverse events other than alopecia that are considered related to prior treatment have not resolved below Grade 1 [Peripheral neurotoxicity (CTCAE: Peripheral motor/sensory neuropathy) is not excluded if Grade 2 or less.]
20) Hypersensitivity to the active ingredient of the investigational product has been confirmed.
21) Patients who have inherited disorders of lactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
22) Women who are pregnant, breastfeeding (not enrolled if they discontinued breastfeeding) or may be pregnant
23) It is considered difficult to participate in the study because of concomitant psychosis or psychiatric symptoms.
24) The attending physician judges that enrollment in the clinical trial is inappropriate.

Related Information

• Primary Sponsor: Kawamoto Yasuyuki
• Secondary Sponsor: Komatsu Yoshito,Morizane Chigusa
• Source(s) of Monetary Support: Takeda Pharmaceutical Company Limited,Japan Agency for Medical Research and Development