Clinical Trial Testing the Safety of Four Ramucirumab Doses Given as Second Line Treatment to Patients with Stomach Cancer

• Register: EUCTR
• Last refreshed on: 25 May 2021
• Main ID: EUCTR2014-003791-23-PL
• Date of registration: 21/05/2015
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: Clinical Trial Testing the Safety of Four Ramucirumab Doses Given as Second Line Treatment to Patients with Stomach Cancer
• Scientific title: Protocol I4T-MC-JVDB Randomized Phase 2 Trial Evaluating Pharmacokinetics and Safety of Four Ramucirumab Dosing Regimens in Second Line Gastric or Gastroesophageal Junction Adenocarcinoma
• Date of first enrolment: 27/06/2015
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003791-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, France, Hungary, New Zealand, Poland, Romania, Russian Federation, Slovakia, United Kingdom, United States

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
1. The patient has a histopathologically or cytologically confirmed diagnosis of gastric or GEJ (Siewert Types I-III) adenocarcinoma.

2. The patient has documented disease progression during or within 4 months after the last dose of first-line chemotherapy for metastatic disease, or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy.

3. The patient received combination chemotherapy prior to disease progression.

4. The patient has metastatic disease or locally advanced and unresectable disease that is measurable or nonmeasurable, but is evaluable disease by radiological imaging

5. Patients are eligible if they are considered not appropriate, for whatever reason, for treatment with ramucirumab in combination with paclitaxel

6. The patient has adequate organ function.

7. The patient is at least 18 years old (or of an acceptable age according to local regulations, whichever is older) and has provided written informed consent prior to any study-specific procedures.

8. The patient has an estimated life expectancy of at least 12 weeks in the judgment of the investigator.

9. The patient has resolution to maximum Grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (NCI 2009), of all clinically significant toxic effects of previous anticancer therapy.

10. The patient, if male, is sterile or agrees to use a reliable method of birth control and to not donate sperm during the study and for at least 12 weeks following the last dose of study treatment. The patient, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control during the study and for 12 weeks following the last dose of study treatment.

11. The patient, if female and of child-bearing potential, must have a negative serum or urine pregnancy test within 7 days prior to randomization.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

Exclusion criteria:
1. The patient has squamous cell or undifferentiated gastric cancer.

2. Within 7 days prior to randomization, the patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents or with other anti-platelet agents.

3. The patient received radiotherapy within 14 days prior to randomization.

4. The patient received >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ adenocarcinoma.

5. The patient received previous treatment with agents targeting the VEGF/VEGF Receptor 2 signaling pathway, including previous exposure to ramucirumab

6. The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.

7. The patient has a significant bleeding disorder or vasculitis or had a Grade > 3 bleeding episode within 12 weeks prior to randomization.

8. The patient experienced any arterial thromboembolic event within 6 months prior to randomization.

9. The patient has symptomatic congestive heart failure or symptomatic or poorly controlled cardiac arrhythmia.

10. The patient has uncontrolled hypertension.

11. The patient underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization.

12. The patient has a history of: gastrointestinal perforation, fistula, inflammatory bowel disease, Crohn’s disease, acute or subacute bowel obstruction or history of chronic diarrhea, cirrhosis at a level of Child-Pugh B.

13. The patient received any previous investigational therapy within 4 half-lives of the investigational agent prior to randomization

14. The patient has a serious illness or medical condition, or any condition (for example, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures.

15. The patient is pregnant or breastfeeding.

16. The patient has a concurrent active malignancy.

17. The patient has a serious nonhealing: (a) wound, (b) peptic ulcer, or (c) bone fracture, within 28 days prior to randomization.

18. The patient is receiving therapeutic anticoagulation therapy with an agent other than low molecular weight heparin or a similar agent.

19. The patient experienced any Grade 3 or 4 venous thromboembolic event (VTE) that is considered by the investigator to be life-threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 6 months prior to randomization.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Second Line Gastric or Gastroesophageal Junction Adenocarcinoma
MedDRA version: 20.0 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Cyramza
Product Name: ramucirumab
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 947687-13-0
Other descriptive name: RAMUCIRUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: The final analysis of the primary endpoints will occur after all randomized patients have completed at least 3 cycles of ramucirumab or discontinued for any reason prior to completing 3 cycles.

Main Objective: Evaluate ramucirumab PK following various dose regimens. Assess the safety for each dose group of ramucirumab in patients with advanced gastric cancer, whose disease has progressed during or following prior combination chemotherapy

Primary end point(s): 1. PK endpoint: Minimum ramucirumab concentration in serum.
2. Safety endpoints evaluated will include but are not limited to the following:
• TEAEs, AESIs, SAEs, and hospitalizations
• Clinical laboratory tests, vital signs, and physical examinations

Secondary Objective: Blood samples for immunogenicity testing will be collected to determine antibody production against ramucirumab.
PFS at the first 6-week assessment, as determined by investigator assessment per RECIST 1.1

Secondary Outcome(s)

Secondary end point(s): 1. Blood samples for immunogenicity testing will be collected to determine antibody production against ramucirumab.
2. PFS at the first 6-week assessment, as determined by investigator assessment per RECIST 1.1

Timepoint(s) of evaluation of this end point: All Secondary and Exploratory Endpoints will be analyzed at the same time as the Primary Endpoint: after all randomized patients have completed at least 3 cycles of ramucirumab or discontinued for any reason prior to completing 3 cycles.

Secondary ID(s)

I4T-MC-JVDB

2014-003791-23-HU

Source(s) of Monetary Support

Eli Lilly and Company

Ethics review

Status: Approved
Approval date: 26/05/2015
Contact:

Results

• Results available: Yes
• Date Posted: 17/06/2020
• Date Completed: 05/06/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003791-23/results