Comparing the Efficacy and Safety of Intra-peritoneal Infusion of Catumaxomab and Treatment of Investigator Choice in Patients With Advanced Gastric Carcinoma With Peritoneal Metastasis

Stomach Neoplasms Clinical Trial

Official title:

A Two-stage,Multi-center,Open-label, Randomized,Controlled Trial Comparing the Efficacy and Safety of Intra-peritoneal Infusion of Catumaxomab and Treatment of Investigator Choice in Patients With Advanced Gastric Carcinoma With Peritoneal Metastasis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04222114
• Other study ID #: LP0190415
• Status: Recruiting
• Phase: Phase 3
• Start date: October 6, 2020
• Est. completion date: August 31, 2023

Study information

• Verified date: January 2023
• Source: LintonPharm Co.,Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A total of 297 subjects are estimated to enroll in the study, with 15 eligible subjects enrolled in the 1st stage at most and 282 evaluable subjects in the 2nd stage. All subjects are adult patients with age over 18-year-old; they must be diagnosed with recurrent or metastatic gastric cancer with peritoneal metastasis at the time of enrollment; and failed at least prior two standard systemic anti-cancer therapies for recurrent or metastatic gastric cancer, before enrollment. In the first stage, pharmacokinetic characteristics and preliminary safety of catumaxomab will be explored in Asian patients with gastric cancer ; in Cohort A, the enrolled subjects will receive the first infusion at 10μg on day 1, which will be increased to 20 μg, 50 μg and 150 μg on days 4, 8 and 11, respectively. 42 days are defined as a cycle. From the second cycle, catumaxomab will be changed to 20 μg, 50 μg, 150 μg on days 1, 4, 8 respectively. In Cohort B, 28 days are defined as a cycle. It is estimated to enroll 6 subjects in each cohort first. In the second stage, approximate 282 subjects who meet the enrollment criteria are randomized into either catumaxomab infusion group (catumaxomab group) or treatment of investigator choice group (IC group), at a ratio of 2:1. Subjects at the first and second stages will continue the treatment until one of the following conditions occurs:1)Significant progression of tumor lesions, including but not limited to peritoneal metastases lesions and/or ascites; 2)Intolerable toxicity; 3)The investigator believes that patients need to withdraw from the study and receive other treatment;4)death;5)Withdrawal of informed consent.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 282
• Est. completion date: August 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Signed and dated informed consent forms have been provided.

2. Willing to be complaint with the study procedures during the study.

3. Male or female, age=18years old when signing informed consents.

4. Histologically or cytologically confirmed as gastricadeno carcinoma.

5. Evaluable and/or non-evaluable lesions according to RECISTV1.1 criteria.

6. Diagnosed as gastric cancer with peritoneal metastases (Imaging finding, previous surgicalpathology, ascites/peritoneal effusion cytology positive).

7. Treatment failure after receiving at least prior two standard systemic anti-cancer therapies for recurrent or metastatic gastric cancer.

8. Recovered from any toxicity due to previous treatment (Grade 0-1 according to NCI-CTCAEv5.0).

9. Estimated survival length=3months.

10. Eastern Oncology Cooperative Group(ECOG) performance status 0-2.

11. The laboratory test values during the screening period are in accordance with the following table:ANC(absolute neutrophil count)= 1.5 × 10^9/L, Hemoglobin= 80 g/L,Platelet= 100 × 10^9/L, Lymphocyte percentage=13%,Serum Bilirubin= 1.25 x ULN(or 2.5 x ULN if there is Gilbert), AST and ALT = 2.5 × ULN without liver metastasis(or= 5 × ULN if liver metastasis ),Serum creatinine = 2.0 mg/dL (or Calculated creatinine clearance=30 mL/min).

12. For women of childbearing potential: use an efficient method for contraception at least 1 month prior to screening and agree to use this method for contraception during the study period and extended period specified after the study intervention.

13. For men with fertility potential: use condoms or other methods to ensure effective contraception for sexual partners.

Exclusion Criteria:

1. Known or suspected of being allergic to catumaxomab or similar antibodies.

2. Previously received anti-tumor treatments, including other anti-tumor investigational drugs, chemotherapy, immunotherapy, biological agents, hormone therapy, radiation therapy (except local radiation therapy for pain relief), etc., the interval between the last treatment and the first peritoneal infusion is = 21days.

3. There is extensive liver metastasis(the tumor volume is estimated to be=50% of the total liver volume by imaging).

4. Known tumor in tra-cranial metastases.

5. The following diseases have not been resolved to CTCAE grade 0-1 3 days before the

first infusion:

• Uncontrolled acute and chronic infections such as pneumonia, biliary infection, hepatitis B virus infection and hepatitis C virus infection,etc.;
• Acute or chronic pancreatitis;
• Diarrhea;
• Dyspnea

6. NYHA Class 3 or 4.

7. Symptoms and signs of related cardiovascular diseases: including myocardial infarction, congestive heart failure,arrhythmia.

8. Known cerebrovascular accidents.

9. Intestinal obstruction occurred 30 days before the first dose.

10. Imaging diagnosis of portal vein obstruction, including tumor compression or portal thrombosis,cancer thrombus.

11. History of autoimmune diseases (e.g.,inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autologous hemolytic anemia, rheumatoid arthritis,etc.).

12. Patients with known HIV serology positive, hepatitis C infection and/or hepatitis B (Except the patients with HepBsAg or core antibody positive and responding to antiviral therapy against hepatitis B who are allowed to participate in the study; Notes: HepBsAg-negative patients at screening, or patients are undergoing treatment with interferon-2a [IFN] or peginterferon-2a [Peg-IFN] and hepatitis B virus [HBV] DNA < 2000 international units [IU], or subjects who are receiving nucleoside [acid] analogues at screening and HBV DNA below the lower limit of normal [LLN] are eligible to participate in the study).

13. Pregnancy or breast feeding during study treatment and follow-up.

14. Patients with confirmed history of neurological or psychotic disorders, including epilepsy or dementia.

15. Other serious systemic conditions that may limit the patient's participation in this study (eg uncontrolled diabetes, cardiovascular and cerebrovascular disease, severe gastrointestinal disease,etc.).

16. Any other condition that, in the discretion of the investigator will make patients exposed to unnecessary risks and unsuitable for participation in this clinical study.

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Stomach Neoplasms

Intervention

Drug:
• Catumaxomab
The starting dose of catumaxomab for intra-peritoneal infusion will be 10µg, gradually increased to 20µg, 50µg and 150µg, respectively. From the second cycle, catumaxomab will be changed to 20µg,50µg,150µg on days 1,4 and 8.
• The treatment of investigator choice
the localized supportive treatment which has been approved or recommended by local gastric cancer guidance to treat the peritoneal metastasis.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	The First Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	The First Bethune Hospital of Jilin University.	Jilin	Jilin
China	Henan Cancer Hospital	Zhengzhou	Henan
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi-do
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chi Mei Hospital, Liouying	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan

Sponsors (1)

Lead Sponsor	Collaborator
LintonPharm Co.,Ltd.

Countries where clinical trial is conducted

China,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Defined as the time from randomization to death for anyreason.	1 year
Secondary	Progression Free Survival (PFS)	According to RECIST V1.1 criteria, defined as the timefrom randomization to progression disease (PD) or death for any reason,which ever occurs first.	1 year
Secondary	Progression free interval of peritoneal metastatic lesions	to subjects with =300 ml of ascites, defined as the time from first intra-peritoneal infusion to ascites progression based on the five--point method2; to subjects without ascites or <300 ml, it is defined as the time from the first intra-peritoneal infusion to thetimeof progression oftheintra-peritoneal lesion according to theRECISTV1.1 criteria.	1 year
Secondary	Objective Response Rate (ORR)	According to RECIST V1.1 criteria, defined as the proportion of subjects with response achieving CR or PR;	1 year
Secondary	Clinical Benefit Rate(CBR)	According to RECIST V1.1 criteria,defined as the proportion of subjects with response achieving SD,PR or CR;	1 year
Secondary	Duration of Response (DoR)	According to RECIST V1.1 criteria, defined as the time from the response to the confirmation of PD	1 year
Secondary	Ascites Remission Duration	Defined as the time from the 1st as cites remission to as cites progression,according to the five-point method.	1 year
Secondary	The incidence and severity of treatment-emergent adverse events (TEAEs) in the catumaxomab and IC groups	Compared according to the National Cancer Institute Common Terminology Standard for Adverse Events (NCI-CTCAE)v5.0.	1 year
Secondary	Incidence of DLT	it will be evaluated in the first stage only. It is defined as the incidence of DLT from the first infusion to 6 weeks after wards.	1 year
Secondary	The incidence of anti-drug antibodies(ADA) to catumaxomab in serum	The incidence of anti-drug antibodies(ADA) to catumaxomab in serum	1 year
Secondary	Tendency of theperipheral blood lymphocyte counts change associated with the intra-peritoneal infusion of catumaxomab	Tendency of theperipheral blood lymphocyte counts change associated with the intra-peritoneal infusion of catumaxomab	1 year