Unique ID issued by UMIN | UMIN000025947 |
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Receipt number | R000029783 |
Scientific Title | Phase I/II multicenter trial of paclitaxel, ramucirumab and nivolumab for metastatic gastric cancer patients who progressed on chemotherapy with fluoropyrimidine plus platinum |
Date of disclosure of the study information | 2017/02/03 |
Last modified on | 2021/08/09 18:12:32 |
Phase I/II multicenter trial of paclitaxel, ramucirumab and nivolumab for metastatic gastric cancer patients who progressed on chemotherapy with fluoropyrimidine plus platinum
Phase I/II trial of paclitaxel, ramucirumab and nivolumab for advanced gastric cancer patients
Phase I/II multicenter trial of paclitaxel, ramucirumab and nivolumab for metastatic gastric cancer patients who progressed on chemotherapy with fluoropyrimidine plus platinum
Phase I/II trial of paclitaxel, ramucirumab and nivolumab for advanced gastric cancer patients
Japan |
Gastric cancer
Gastroenterology | Hematology and clinical oncology |
Malignancy
NO
Phase I: To determine Maximum Tolerated Dose: MTD, Dose Limiting Toxicity: DLT, Recommended Dose: RD of paclitaxel, ramucirumab and nivolumab
Phase II: To evaluate efficacy of paclitaxel, ramucirumab and nivolumab at RD level
Safety
Exploratory
Explanatory
Phase I,II
Phase I: DLT
Phase II: 6 months progression -free survival
Phase I: Safety
Phase II: Overall response rate: ORR, Disease control rate: DCR, Progression-free survival: PFS, Overall survival: OS
Interventional
Single arm
Non-randomized
Open -no one is blinded
Uncontrolled
1
Treatment
Medicine |
Level1
Paclitaxel: 80 mg/m2 day1, 8, 15
Ramucirumab:8 mg/kg div day1, 15
Nivolumab: 3 mg/kg div day1, 15
28 days 1 course
Level0
Paclitaxel: 80 mg/m2 day1, 8, 15
Ramucirumab:8 mg/kg div day1, 15
Nivolumab: 1 mg/kg div day1, 15
28 days 1 course
20 | years-old | <= |
Not applicable |
Male and Female
1) Histologically diagnosed as adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma), signet ring cell carcinoma, mucinous carcinoma, hepatoid adenocarcinoma.
2) Unresectable gastric cancer including esophago-gastric junctional cancer)
3) No massive ascites that needs drainage.
4) No brain metastasis
5) To be able to take oral intake
6) Aged 20 years or over
7) ECOG PS 0 or 1
8) One or more measurable lesions
9) Prior chemotherapy with fluoropyrimidine and platinum
10) Adequate organ function
1. Neutrophil count: 1,500/mm3 or above
2. Platelet count: 100,000/mm3 or above
3. Hemoglobin: 8.0 g/dL or above
4. AST(GOT):100 IU/L or less
5. ALT(GPT):100 IU/L or less
6. Total bilirubin: 1.5 mg/dL or less
7. Creatinin: 1.5 mg/dL or less
8. PT-INR: 1.5 or less
9. i. Urinary protein (-) or (1+)
ii. Urinary protein (2+) or more : Measure proteinuria for 24 hours and urinary protein 1g or less / 24 hour
11) Blood pressure under control
12) Written informed consent
1) Prior therapy with anti PD-1/PD-L1/CTLA-4 antibody or treatment targeting T cell
2) Chemotherapy within 14 days prior to enrollment
3) Treatment under investigation within 28 days prior to enrollment
4) Prednisolone 10mg or more/immunosuppressing therapy within 14 days prior to enrollment
5) Other active cancer
6) Active infecton
7) Fever of 38 Centigrade or above
8) Pregnancy
9) HBsAg+ or HCVAb+
10) HIV-1 Ab+ or HIV-2 Ab+ or HTLV-1 Ab+
11) Serious comorbidity
12) Consent to contraception
43
1st name | Takako |
Middle name | |
Last name | Nakajima |
St. Marianna University School of Medicine Hospital
Department of Clinical Oncology
216-8511
2-16-1 Sugao Miyamae-ku Kawasaki Kanagawa
044-977-8111
tnakajima@marianna-u.ac.jp
1st name | Yuko |
Middle name | |
Last name | Tanno |
St. Marianna University School of Medicine
Department of Clinical Oncology
216-8511
2-16-1 Sugao Miyamae-ku Kawasaki Kanagawa
044-977-8111
kenkyug-rinshoshuyou@googlegroups.com
St. Marianna University School of Medicine Hospital
Department of Clinical Oncology
ONO PHARMACEUTICAL CO., LTD.
Profit organization
St. Marianna University School of Medicine Hospital
2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan
044-977-8111
k-sienbu.mail@marianna-u.ac.jp
NO
聖マリアンナ医科大学病院 腫瘍内科
千葉県がんセンター 臨床試験推進部
愛知県がんセンター中央病院 薬物療法部
独立行政法人国立病院機構四国がんセンター 消化器内科
2017 | Year | 02 | Month | 03 | Day |
http://www.oncology-mari.com/outline
Published
https://clincancerres.aacrjournals.org/content/27/4/1029
43
Forty-three patients were enrolled. The recommended dose was determined as level 1. The overall response rate was 37.2% (95% CI, 23.0%-53.5%) and the 6-month PFS rate was 46.5% (80% CI, 36.4%-55.8%; P = 0.067). Median survival time was 13.1 months (95% CI, 8.0-16.6 months). Nivolumab with paclitaxel plus ramucirumab demonstrated promising antitumor activity as second-line treatment for AGC.
2021 | Year | 08 | Month | 09 | Day |
2021 | Year | 02 | Month | 28 | Day |
A total of 43 patients were enrolled between February 2017 and July 2018, and all patients were included in the FAS. The majority of patients were male, with an age range of 38-78 years. Twenty-two patients (51.2%) had PS of 0, TPS was positive in six patients (14.0%), and CPS was >1 in 26 patients (60.5%) and >10 in seven patients (16.3%). MMR and EBER were positive in zero and 4 patients (9.3%), respectively.
Six patients in phase 1 and 37 patients in phase 2 were enrolled. At the primary analysis (January 2019, median follow-up time of 8.2 months), 23 PFS events (53.5%) had occurred. At final analysis with a median follow-up time of 23.2 months (95%CI, 17.4-28.0), thirty-two OS events (74.4%) occurred.
Thirty-nine (90.7%) patients experienced grade >3 treatment-related AEs. The most common grade >3 AE was neutrophil count decrease (33 patients, 76.7%), while febrile neutropenia was observed in seven patients (16.3%). Fourteen (32.6%) patients experienced grade >3 immune-related AEs. There was one treatment-related death from thrombocytopenia.
DLTs (febrile neutropenia and neutropenia over a period of 8 days) were observed in two of six patients in level 1, and the RD was determined at level 1. All patients included in the phase 2 part were treated at the RD. Six-month PFS was 46.5% (80% CI, 36.4-55.8; P = 0.067), which means primary endpoint was met. OS at 12 and 18 months was 55.8% (95% CI, 39.8-69.1) and 32.1% (95% CI, 18.2-46.8), respectively.
Median PFS was 5.1 months (95% CI, 4.5-6.5 months): 6.4 months (95% CI, 4.2-7.9 months) in patients with CPS >1 and 5.1 months (95% CI, 2.6-6.7 months) in patients with CPS <1; 6.4 months (95% CI, 1.0-6.9 months) in patients with CPS >5 and 5.9 months (95% CI, 4.6-6.9 months) in patients with CPS <5; 6.7 months (95% CI, 1.0-8.8 months) in patients with CPS >10 and 5.5 months (95% CI, 4.2-6.7 months) in patients with CPS <10; and 5.8 months (95% CI, 4.2-7.9 months) in patients with PS 0 and 4.9 months (95% CI, 3.2-6.4 months) in patients with PS 1.
Thirty-two OS events (74.4%) occurred and median survival time was 13.1 months (95% CI, 8.0-16.6 months): 13.8 months (95% CI, 8.0-19.5 months) in patients with CPS >1 and 8.0 months (95% CI, 4.8-24.1 months) in patients with CPS <1; 13.1 months (95% CI, 5.1 months-not reached) in patients with CPS >5 and 14.9 months (95% CI, 7.4-19.5 months) in patients with CPS <5; 13.8 months (95% CI, 8.0 months-not reached) in patients with CPS >10 and 13.0 months (95% CI, 7.1-18.6 months) in patients with CPS <10; and 14.4 months (95% CI, 7.7-28.0 months) in patients with PS 0 and 8.0 months (95% CI, 4.8-16.6 months) in patients with PS 1.
DCR was 83.7% (95% CI, 69.3-93.2). ORR was 37.2% (95% CI, 23.0-53.5): 46.2% (95% CI, 26.6-66.6) in patients with CPS >1 and 30.8% (95% CI, 9.1-61.4) in patients with CPS <1; and 45.5% (95% CI, 24.4-67.8) in patients with PS 0 and 28.6% (95% CI, 11.3-52.5) in patients with PS 1.
Completed
2017 | Year | 01 | Month | 20 | Day |
2016 | Year | 12 | Month | 12 | Day |
2017 | Year | 02 | Month | 03 | Day |
2019 | Year | 07 | Month | 31 | Day |
2021 | Year | 02 | Month | 28 | Day |
2017 | Year | 02 | Month | 01 | Day |
2021 | Year | 08 | Month | 09 | Day |
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029783
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