Phase II study of nab-paclitaxel plus ramucirumab in combination with nivolumab in unresectable advanced or recurrent gastric cancer after progression to first-line therapy including fluoropyrimidine, platinum, and anti-PD-1/PD-L1 antibody.

JRCT ID: jRCT2031220448

Registered date:17/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Unresectable advanced or recurrent gastric cancer
• Date of first enrollment: 21/02/2023
• Target sample size: 45
• Study type: Interventional

Intervention(s)

Nab-paclitaxel 100 mg/m^2 IV over 30 minutes every 1 week (2 weeks if given for 3 consecutive weeks)
Ramucirumab 8 mg/kg IV over 1 hour every 2 weeks (first dose)/30 minutes (second and subsequent doses)
Nivolumab 240 mg/body IV over 30 minutes every 2 weeks

Outcome(s)

• Primary Outcome: 6-month progression-free survival rate

Secondary Outcome

Response rate
Disease control rate
Progression-free survival
Overall Survival
Duration of response
Time to response
Adverse event rate

Key inclusion & exclusion criteria

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

Include criteria

1.Histologically diagnosed as adenocarcinoma, signet ring cell carcinoma, or mucinous carcinoma.
2.Unresectable advanced or recurrent gastric cancer.
3.No severe ascites on CT imaging that extends beyond the pelvic cavity to the upper abdomen. No massive ascites or pleural effusion requiring drainage.
4.The patient is capable of oral intake.
5.Age at the time of consent is 18 years or older.
6.ECOG-PS:0-1.
7.Have at least one measurable lesion on contrast-enhanced CT within 28 days prior to enrollment.
8.Refractory to combination therapy including pyrimidine fluoride, platinum, and anti-PD-1/PD-L1 antibody or intolerant to drugs other than anti-PD-1/PD-L1 antibody for unresectable advanced or recurrent gastric cancer with one prior regimen.
9.Laboratory tests performed within 14 days prior to enrollment meet the criteria. However, the patient must not have received granulocyte colony stimulating factor (G-CSF product) administration or blood transfusion within 14 days prior to blood collection.
10.For female of childbearing potential, have agreed to dual contraception, prohibition of egg donation and prohibition of breast feeding from the time of consent until at least 6 months after the last dose of any investigational drug. For male, have agreed to dual contraception and prohibition of sperm donation from the start of investigational drug administration until at least 6 months after the last dose of any investigational drugs.
11.Able to provide peripheral venous blood and urine samples for biomarker studies.
12.Written consent to participate in the study has been obtained from the patient.

Exclude criteria

1.The patient has an active overlapping cancer.
2.Clear metastasis to the central nervous system by contrast-enhanced CT or MRI within 28 days prior to enrollment.
3.Active infection requiring systemic treatment.
4.Pregnant, possibly pregnant, or lactating women.
5.Positive for HIV antibody, HBs antigen, or HCV antibody.
6.HBs antigen negative, HBs or HBc antibody positive, and HBV-DNA quantification positive.
7.Complicated interstitial lung disease, pneumonitis, pulmonary fibrosis, or a history of these diseases.
8.Grade 3 or higher (CTCAEv5.0) immune-related adverse events related to previous PD-1/PD-L1 antibody therapy or immune-related adverse events leading to permanent discontinuation of anti-PD-1/PD-L1 antibody.
9.Patient has a defined pre-existing or concomitant disease.
10.Prior therapy with angiogenesis inhibitors or taxanes.
11.Prior therapy with other T-cell-regulating agents except for initial chemotherapy with anti-PD-1 or anti-CTLA-4 antibodies for unresectable advanced or recurrent gastric cancer.
12.Have hypertension that is poorly controlled by standard medical management.
13.Receiving systemic corticosteroids or immunosuppressive drugs within 14 days prior to enrollment.
14.Receiving systemic antineoplastic therapy within 7 days prior to enrollment.
15.Receiving radiation therapy within 28 days prior to registration. However, in the case of irradiation for bone metastases, irradiation was performed within 14 days prior to enrollment in the study.
16.Received live or attenuated attenuated vaccine within 28 days prior to enrollment.
17.Has a history of organ transplantation, including hematopoietic stem cell transplantation.
18.Has a history of severe hypersensitivity to nivolumab, ramucirumab, nab-paclitaxel, paclitaxel, or albumin.
19. Patient has psychosis or psychiatric symptoms that interfere with daily life and make participation in the study difficult.

Related Information

• Primary Sponsor: Shoji Hirokazu
• Source(s) of Monetary Support: ONO PHARMACEUTICAL CO., LTD.