Phase 1b/2 trial for venadaparib in combination with paclitaxel and ramucirumab as a second-line therapy for gastric cancer with homologous recombination repair deficiency
- Conditions
- Neoplasms
- Registration Number
- KCT0009067
- Lead Sponsor
- ational Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 75
1. Pathologically or cytologically confirmed gastric adenocarcinoma
2. You are at least 19 years of age on the date you sign the consent form
3. Patients with ECOG performance status 0-2
4. Patients with expected survival > 12 weeks.
5. Persons with confirmed adequate organ function, as defined in the applicable section below;
1) Absolute neutrophil count (ANC) = 1.0 x 109/L (=1,000 per mm3)
2) Platelet count = 100 x 109/L (=100,000 per mm3)
3) Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). (Gilbert's syndrome is an exception).
4) AST (SGOT)/ALT (SGPT) = 2.5 x institutional UNL (However, if liver metastases = 5x ULN)
5) 24-h urine creatinine clearance or eGFR > 40 mL/min
6. For women, negative pregnancy test or non-fertile women defined as:
1) Medical history of menopause (absence of menstruation for more than 1 year without other medical reasons)
2) Patients who have undergone hysterectomy or bilateral tubal ligation or bilateral oophorectomy
7. Patients who are intolerant to first-line therapy for the treatment of metastatic gastric cancer, show progressive disease after taking first-line therapy, or receive anticancer drugs used as adjuvant chemotherapy or stop (based on the date of the last anticancer drug administration) 6 If disease progression is shown within 12 months (provided that the above anti-cancer therapy (first-line or adjuvant) must include a fluoropyrimidine drug; and in the case of phase 1b, disease progression after administration of two or more anti-cancer drugs administered for the treatment of metastatic gastric cancer) However, if there is a defect in homologous recombination repair described in item 8 below, disease progression after administration of one anticancer drug can also be registered)
8. Homologous recombination repair defect in whole-length exome genome test or overexpression of CDK8/19 in proteomic analysis (but not applicable in group 1b)
- HRD score of 42 or higher or HRDetect 0.7 or higher on whole exome sequencing suggests homologous recombination repair defect
-When a pathogenic germline/somatic mutation is found in one of the genes
1. As of the first day of administration of this clinical trial drug (Cycle 1 Day 1), the last day of systemic anticancer treatment (including immunotherapy
and small molecule targeted therapy) was less than 14 days.
B, the last administration date of monoclonal antibody is less than 28 days, or the last administration date of nitrosourea/mitomycin C is less than
42 days (even if the relevant period has not elapsed)
Obtaining consent and conducting screening tests are possible)
2. History of primary cancer other than stomach cancer
However, exceptions are made in the following cases:
1) Patients with cancer that has undergone curative treatment who have been disease-free for more than 3 years and have a low risk of recurrence
2) Patients who are currently disease-free with cured skin cancer (non-melanoma skin cancer, lentigo maligna)
3) Patients with cured in situ carcinoma who are currently disease-free
3. Any condition, treatment or history of the test subject that, in the researcher's judgment, makes it difficult to evaluate the clinical trial results.
4. Uncontrolled active infection, symptomatic heart failure, uncontrolled hypertension/unstable angina/arrhythmia, active bleeding tendency, active
hepatitis, impairing written consent.
Mental illness or social situation that causes
5. Patients with a history of leptomeningeal metastasis.
6. Patients with brain metastases or spinal nerve compression whose symptoms are not controlled (patients whose symptoms have stabilized after
discontinuing anticonvulsants at least 14 days prior to administration of the clinical trial drug can be registered)
7. Uncontrolled seizures
8. Pregnant or potentially pregnant women and lactating women, men or pregnant women who are not willing to use appropriate contraception until
180 days after the end of the clinical trial.
9. Patients who have ever received PARP inhibitors
10. Patients who have received taxane as treatment for metastatic gastric cancer
11. Dialysis patients
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase 1b: Safety evaluation and RP2D determination of venadaparib and paclitaxel/ramucirumab combination therapy, Phase 2: Response rate evaluation of venadaparib and paclitaxel/ramucirumab combination therapy as second-line therapy in gastric cancer deficient in homologous recombination repair
- Secondary Outcome Measures
Name Time Method Phase 1b: 1) Response rate and response period as a second-line treatment for stomach cancer 2) Progression-free survival (PFS) as a second-line treatment for stomach cancer 3) Overall survival (OS) as a second-line treatment for stomach cancer Phase 2: 1) Duration of response as a second-line treatment for homologous recombination repair defective gastric cancer 2) Progression-free survival (PFS) and overall survival (OS) as second-line therapy for homologous recombination repair defective gastric cancer