Camrelizumab, Apatinib and Nab-paclitaxel as Second-line Treatment in Advanced Gastric Cancer

This is a Phase I/II , Open-label , Investigator-initiated Trail of Camrelizumab (an Anti-PD-1 Inhibitor), Apatinib (VEGFR2 Inhibitor) and Nab-paclitaxel as Second-line Treatment in Advanced Gastric Cancer The study was designed in two stages, the first stage was the tolerance observation stage, and the second stage was the curative effect expansion stage.

The first part of the study is the Dose-finding Phase designed to establish the safety of Camrelizumab, Apatinib and Nab-paclitaxel at different dose Levels(125 mg/m2, iv. q2w, 150 mg/m2, iv. q2w, 175 mg/m2, iv. q2w or 200 mg/m2, iv. q2w). The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses .

This study aims to evaluate the safety and efficacy of Camrelizumab, Apatinib and Nab-paclitaxel in the Second-line treatment of advanced Gastric Cancer.

Study Overview

• Status: Unknown
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Drug: Camrelizumab, Apatinib and Nab-paclitaxel

Detailed Description

This trial investigated the safety and efficacy of Camrelizumab, Apatinib and Nab-paclitaxel as Second-line Treatment in Advanced Gastric Cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100853
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Guanghai Dai, PhD; Phone Number: 13801232381; Email: daigh301@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Age: more than 18 years old, male or female;
• 2.Pathologically diagnosed with advanced gastric cancer (including adenocarcinoma of the gastroesophageal junction) with measurable metastases outside the stomach (measuring ≥ 10mm on spiral computed tomography(CT) scan, satisfying the criteria in Response Evaluation Criteria In Solid Tumors (RECIST) 1.1);
• 3.Failure of prior therapy (during or after treatment) in patients who have received at first line chemotherapy regimens(platinum - based regimens);
• 4.Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1;
• 5.Major organ function has to meet the following criteria: Hemoglobin (HB) ≥ 80g / L, ANC ≥ 1.5 × 109 / L, PLT ≥ 90 × 109 / L, ALT and AST ≤ 2.5 × ULN, liver metastases, the ALT and AST≤5 × ULN, Bilirubin ≤ 1.5 times the upper limit of normal (ULN), Serum creatinine ≤ 1.5 times the upper limit of normal (ULN),
• 6.An expected survival of ≥ 3 months;
• 7.Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 12 week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 12 week post the last administration of study drug;
• 8.Patient has to voluntarily join the study and sign the Informed Consent Form for the study.

Exclusion Criteria:

• 1．Other malignancies have been diagnosed within 5 years prior to the first use of the study drug, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or cervical and/or breast cancer in situ which have been effectively treated;
• 2．Subjects are using immunosuppressive agents.
• 3．Confirmed that Camrelizumab, Apatinib, Nab-paclitaxel and/or its accessories allergy;
• 4．Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
• 5．Peripheral neuropathy >1 grade;
• 6．Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; Coronary heart disease greater than Class Ⅰ; Ⅰ-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class Ⅰ cardiac dysfunction; Patients with positive urinary protein;
• 7．Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 2 months;unresected primary lesion in stomach with positive fecal occult blood test (+), ulcerated gastric carcinoma with massive alimentary tract bleeding risk judged by PIs based on gastric endoscopy result;
• 8．Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed;
• 9．Associated with CNS (central nervous system) metastases;
• 10．Pregnant or lactating women;
• 11．With psychotropic drug abuse history and can't get rid of or mental disorder patients;
• 12．Participated in other clinical trials within 4 weeks;
• 13．Any other condition that might place the patient at undue risk or preclude a patient from completing the study;
• 14．Other conditions regimented at investigators' discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camrelizumab, Apatinib and Nab-paclitaxel; Camrelizumab was administered 200mg iv every 2 weeks, Apatinib 250 mg p.o. qd Nab-paclitaxel 125 mg/m2, 150 mg/m2, 175 mg/m2 or 200 mg/m2, iv. q2w	Drug: Camrelizumab, Apatinib and Nab-paclitaxel; Camrelizumab was administered 200mg iv every 2 weeks, Apatinib was administered 250 mg p.o. qd Nab-paclitaxel was administered 125 mg/m2, 150 mg/m2, 175 mg/m2 or 200 mg/m2, iv. q2w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD /DLT (phase I)	Maximum Tolerated Dose/Dose Limiting Toxicity	Within four weeks after administration
ORR(phase II)	Overall Response Rate	from the first drug administration up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (phase I/II)	adverse events/serious adverse events	from the first drug administration to within 90 days for the last drug dose
PFS(phase I/II)	Progression-Free-Survival	from the first drug administration up to two years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Anticipated): May 12, 2021
• Study Completion (Anticipated): May 12, 2022

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (Actual): December 2, 2019

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 1, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Apatinib
• Other Study ID Numbers: Camrelizumab GC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No