Pegliposomal Doxorubicin and 5-fluorouracil as Second Line Therapy for Metastatic Gastric Cancer

Phase II Study of Pegliposomal Doxorubicin and 5-fluorouracil Compared With Irinotecan as Second Line Therapy for Metastatic Gastric Cancer.

For second-line chemotherapy for metastatic gastric cancer, single-agent irinotecan is the standard treatment. Anthracyclines are active but lack well designed investigations. The combination of epirubicin, fluorouracil and cisplatin (or oxaliplatin) are widely used in Europe. However, traditional anthracyclines are more cardiotoxic; and (Pegliposomal Doxorubicin) PLD, as a new liposome dosage form of doxorubicin, has better cardiac safety. Therefore, we designed this phase II trial with PLD and 5-Fu to compare irinotecan monotherapy in the second-line treatment.

Study Overview

• Status: Unknown
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Irinotecan; Drug: DOXOrubicin Liposome Injection; Drug: 5fluorouracil

Detailed Description

Patients with metastatic gastric cancer failed to first-line therapy will be radomized to arm A with PLD and 5-Fu and arm B with irinotecan single agent therapy. Both regimens will be treated every 2 weeks until disease progression or untolerable toxicity. Efficacy will be assessed every 3 cycles and safety will be evaluated every cycle.

• Study Type: Interventional
• Enrollment (Anticipated): 136
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaohui Zhai, MD; Phone Number: 862038285497 862038285497; Email: zhaixh@mail.sysu.edu.cn
• Study Contact Backup: Name: Shanshan Li; Phone Number: 862038285497 862038285497; Email: lishsh89@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Recruiting
      • Jian Xiao
      • Contact: Jian Xiao, MD; Phone Number: 862038285497 862038285497; Email: xiaoj26@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years old;
2. Metastatic gastric cancer progressed on first-line treatment;
3. Expected survival time ≥ 3 months;
4. At least one evaluable target lesion according to the solid tumor evaluation criteria (RECIST) version 1.1;
5. ECOG PS 0~2;
6. Adequate bone marrow function reserve: white blood cell count ≥ 3.0 × 10*9 / L, neutrophil count ≥ 1.5 × 10*9/ L; platelet count ≥ 100 ×10*9/ L; hemoglobin ≥ 90 g / L;
7. Adequate liver and renal function reserve: AST and ALT ≤ 2.5 times the upper limit of normal value, total bilirubin ≤ 2 times the upper limit of normal value; serum creatinine ≤ 1.5 times the upper limit of normal value;
8. LVEF ≥ 55 %;
9. Be able to understand the research process, volunteer to participate in the study, and sign an informed consent form.

Exclusion Criteria:

1. Patients known to be allergic to active or other components of chemotherapeutic drugs;
2. Patients who have been treated with PLD or irinotecan in the past;
3. According to the researcher's judgment, other anti-tumor treatments such as radiotherapy and surgical resection are required during chemotherapy;
4. Those who are not expected to be able to tolerate chemotherapy with severe heart disease or discomfort;
5. d-MMR or MSI-H or Her-2 overexpression;
6. Severe or uncontrolled infections or diabetes;
7. History of other malignacis in the past 5 years (except for cured cervical carcinoma in situ or basal cell carcinoma of the skin);
8. Participated in other clinical trials within 4 weeks prior to the start of the study;
9. Pregnant or lactating women, or women of childbearing age who refuse to take effective contraception during the study.

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
Active Comparator: Irinotecan alone; 150 mg/m2 iv drip d1; Repeat every 14 days.	Drug: Irinotecan; 150 mg/m2 ivdrip every 14 days; Other Names: CPT-11
Experimental: Pegliposomal Doxorubicin and 5-FU; Pegliposomal Doxorubicin: 25mg/m2 iv drip d1; 5FU 400mg/m2 iv bolus and 2400 mg/m2 civ 46h d1; Repeat every 14 days.	Drug: DOXOrubicin Liposome Injection; 25 mg/m2 ivdrip every 14 days; Other Names: Pegliposomal Doxorubicin; Drug: 5fluorouracil; 400mg/m2 iv bolus and 2400 mg/m2 civ 46h every 14 days; Other Names: 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Percentage of subjects with tumor shrinkage reaching complete response (CR), partial response (PR) and disease stabilization (SD).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Percentage of subjects with tumor shrinkage reaching complete response (CR) and partial remission (PR).	24 weeks
Progression-Free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease or date of death, whichever occurs first. For target lesions (TL), PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD) of TLs, taking as a reference the smallest SLD recorded since the treatment started, or the appearance of one or more lesions. For non-target lesions (NTL), PD was defined as an unequivocal progression of existing NTLs. Participants were censored at the last date of tumor measurement, the last date in the study drug log, or the date of last follow-up.	1 year
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause. Participants were censored at the last date of tumor measurement, the last date in the study drug log or the date of last follow-up.	2 years
Treatment associated toxicities	According to WHO CTC 3.0	2 years
EORTC Quality of Life Questionnaire-Stomach Cancer Specific (QLQ STO22) Questionnaire Scores	The QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions concerning disease, treatment related symptoms, side effects, dysphagia, nutritional aspects, and questions about the emotional problems of gastric cancer (dysphagia, pain, reflux, eating restrictions, anxiety, dry mouth, body image, and hair loss). The questions are grouped into five scales and 4 single items which are related to the symptoms of the disease. Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.	2 years

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Investigators: Principal Investigator: Jian Xiao, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Pegliposomal Doxorubicin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Fluorouracil; Irinotecan; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: SAHMO205

Drug and device information, study documents

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