A Study of Gentuximab + Paclitaxel in Patients With Advanced Gastric or Gastroesophageal Junction Cancer

An Multi-center, Open-label Phase Ib/II Study of Gentuximab Injection + Paclitaxel in Patients With Advanced Gastric or Gastroesophageal Junction Cancer to Evaluate Tolerability, Safety, Efficacy and Pharmacokinetics.

The objective of the study is to evaluate Tolerability, Safety, and primary Efficacy of Gentuximab Injection at different dosage in combination with Paclitaxel in Advanced Gastric or Gastroesophageal Junction Cancer patients, to ensure adequate treatment dosage for further study. Meanwhile, the study also evaluate Pharmacokinetics of Gentuximab Injection at different dosage in combination with Paclitaxel.

Study Overview

• Status: Unknown
• Conditions: Advanced Gastric or Gastroesophageal Junction Cancer
• Intervention / Treatment: Drug: Gentuximab; Drug: Paclitaxel

Detailed Description

The study includes dose-limiting toxicity （DLT）observing period and randomization period with two cohorts as low-dose group（Gentuximab Injection 8mg/kg+ paclitaxel） and high-dose group（Gentuximab Injection 12mg/kg+ paclitaxel）. During the study，the anti-cancer efficacy, safety and anti-drug antibody were evaluated in all patients. DLT observation is only to subjects enrolled in DLT observation period and it lasts one treatment period. PK were doing in part of subjects.

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Siqin Wang; Email: wangsiqin@gensci-china.com
• Study Contact Backup: Name: Jin Li; Phone Number: 13761222111; Email: tianyoulijin@163.com

Study Locations

• China
  • Shanghai, China
    • Shanghai First People's Hospital
    • Contact: Weiyi Huang
  • Shanghai, China
    • Shanghai East Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Tumor Hospital
      • Contact: Jianwei Yang
  • Guangdong
    • Guangzhou, Guangdong, China
      • The Sixth Hospital of Sun Yat-Sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The Affiliated Tumor Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
      • Contact: Yanhong Gu
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Nong Xu
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital, Zhejiang University School Of Medicine
    • Hangzhou, Zhejiang, China
      • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject can understand the process and methods of the study, complete the study in accordance with the protocol and is willing to sign a written informed consent.
• Male or female. aged between 18 and 75 years
• Histopathologically confirmed advanced advanced gastric or gastroesophageal junction cancer, and Documented progression during first-line fluoropyrimidine- and platinum- containing chemotherapy, or during the 3 months following the last cycle of such chemotherapy (or during the 6 months following the last dose of adjuvant therapy or new adjuvant therapy containing fluoropyrimidine and platinium).
• At least one Measurable lesion.
• ECOG Performance status (PS) score, 0-1 level.
• A life expectancy of >3 months.
• Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin concentration ≥90g/L (allowing blood transfusion); and platelet count ≥80×109/L.
• Adequate hepatic function, as defined by: ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN (liver metastases patients ALT ≤ 5 × ULN, AST ≤ 5 × ULN, TBIL ≤ 3 × ULN).
• Adequate renal function, as defined by: serum creatinine level≤ 1.5 × ULN, or creatinine clearance ≥ 50ml / min when serum creatinine level> 1.5 × ULN.
• Adequate coagulation function, as defined by: International normalized ratio (INR) ≤1.5× ULN, activated partial thromboplastin time (aPTT) ≤1.5 x ULN.
• 24-hour urine protein quantitation is <1g（24-hour urine protein quantitative test should be performed when urine protein ≥1+ is found during screening visit）.
• Subjects (male and female) who have fertility must agree to use reliable contraceptive methods during the trial and in 3 months after the last administration. Female subjects in childbearing age must be negative for blood pregnancy test prior to enrollment.

Exclusion Criteria:

• Previously administrated with anti-angiogenic drugs or paclitaxel.
• Systematic anti-tumor therapy (non-anti-angiogenic drugs or paclitaxel) such as chemotherapy, radiotherapy, macromolecular targeted therapy, immunotherapy, endocrine therapy, etc. within 4 weeks before the first dose of investigational drug, except for the following: nitrourea or mitomycin C is within 6 weeks before the first dose, oral fluorouracil and small molecule targeted drugs are within 2 weeks or 5 half-life of the drug(whichever is longer) before the first dose，Chinese medicine with anti-cancer indications is within 2 weeks before the first dose.
• Has participated in a clinical study of a non-approved experimental agent within 4 weeks prior to screening visit.
• Has undergone major surgery within 4 weeks before screening visit (not including needle biopsy)， or would undergo planned surgery during the study.
• Subject with positive HCV-Ab, Anti-HIV or TP-Ab, or positive HBS-Ag with copies of HBV DNA > ULN.
• Patients with previously confirmed malignant tumors.
• History of arterial thrombosis or deep vein thrombosis within 6 months prior to screening, or a bleeding event no less than Grade level 3 within 2 months prior to screening， or the investigator determines that there is a risk of bleeding.
• History of severe cardiovascular and cerebrovascular diseases.
• Subjects with confirmed brain tumor metastases，but subjects in steady situation can be enrolled.
• Active bleeding confirmed by gastroscopy when fecal occult blood positive (only subjects with primary lesions not removed need to do fecal occult blood test.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 12 months before screening visit.
• Thoracic，abdominal or pericardial effusion that cannot be controlled by repeated drainage or with obvious symptoms.
• Has a nonhealing wound, serious ulcer, or unrecovered bone fracture.
• Active infections requiring systemic treatment, including but not limited to active tuberculosis.
• Using anticoagulation and antiplatelet drugs.
• Female subjects who is pregnant (confirmed by urine or serum pregnancy test) or lactating.
• Has a known serious allergy reaction to recombination monoclonal antibody (MAb) drug, ,or infusion reaction.
• Has known alcohol or drug dependency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 Gentuximab+ Paclitaxel; 8 mg/kg Gentuximab administered intravenously (IV) on D1 and D15（28 days every cycle）+ 80 mg/m² paclitaxel administered IV on D1, D8 and D15	Drug: Gentuximab; Administered intravenously (IV); Drug: Paclitaxel; Administered intravenously (IV)
Experimental: 2 Gentuximab+ Paclitaxel; 12 mg/kg Gentuximab administered intravenously (IV) on D1 and D15（28 days every cycle）+ 80 mg/m² paclitaxel administered IV on D1, D8 and D15	Drug: Gentuximab; Administered intravenously (IV); Drug: Paclitaxel; Administered intravenously (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities (DLT)	Number of Participants With One or More Drug-Related Adverse Events (AEs) defined as DLT in the protocol	Up to 4 Weeks
AEs or SAEs	Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)	Baseline through Study Completion, about 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate（ORR）	Proportion of Participants With CR and PR	Up to 6 cycles (28 days for every cycle)
Progression-free survival (PFS)	The time from randomization to the patient tumor progression or death.	Up to 6 cycles (28 days for every cycle)
Disease control rate (DCR)	Proportion of Participants With CR, PR and SD	Up to 6 cycles (28 days for every cycle)
Time-to-progress (TTP)	The time from randomization to the patient tumor progression.	Up to 6 cycles (28 days for every cycle)
Time-to-failure (TTF)	The time from randomization to the patient withdraw from the study.	Up to 6 cycles (28 days for every cycle)
Anti-drug antibody	Number of Participants With Anti-drug Antibodies	Up to 6 cycles (28 days for every cycle)
Pharmacokinetics Cmax	Maximum Concentration (Cmax)	Cycle 1(day1-day 15)& Cycle 2(day 15-day26) & Cycle 3(day 1) (28 days for every cycle)
Area Under the Concentration-Time Curve (AUC)		Cycle 1(day1-day 15)& Cycle 2(day 15-day26) & Cycle 3(day 1) Cycle 1(day1-day 15)& Cycle 2(day 15-day26) & Cycle 3(day 1) （28 days for every cycle）

Collaborators and Investigators

• Sponsor: GeneScience Pharmaceuticals Co., Ltd.
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Tongji Hospital; The First Affiliated Hospital of Zhengzhou University; The First Hospital of Jilin University; Sixth Affiliated Hospital, Sun Yat-sen University; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai East Hospital; Sir Run Run Shaw Hospital; The First Affiliated Hospital, Zhejiang University School of Medicine; Fujian Tumor Hospital; The Affiliated Tumor Hospital of Harbin Medical University; Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2019
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: July 27, 2019
• First Submitted That Met QC Criteria: August 9, 2019
• First Posted (Actual): August 12, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: GenSci 043 CT

Drug and device information, study documents

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