Phase II Randomized Study of Ramucirumab with or without Paclitaxel in Elderly Patients with Metastatic Gastric Cancer
- Trial ID
- 2024-513515-27-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to assess the **6-month overall survival** and **4-month quality of life** in older patients with advanced gastric cancer, specifically those with **stomach cancer stage IV with metastases**, when treated with ramucirumab alone or in combination with paclitaxel. This evaluation is clinically relevant as it aims to determine the efficacy of these treatment regimens in prolonging survival and maintaining quality of life in a population that may have different tolerability and response profiles due to age-related factors.
Secondary objectives include:
- Evaluating other dimensions of quality of life at 4 months
- Determining the time to deterioration in health-related quality of life
- Assessing the time to degradation of autonomy
- Measuring overall survival
- Monitoring toxicity
- Calculating time to treatment failure
- Evaluating progression-free survival
- Assessing the best tumor response during treatment
- Identifying geriatric prognostic and predictive factors for the efficacy and tolerability of treatment
- Determining prognostic and predictive nutritional factors for treatment tolerance
Participants
The clinical trial focused on patients diagnosed with **stomach cancer stage IV with metastases**. The study population included both male and female participants aged 70 years and older. Participants were required to have a histologically proven unresectable metastatic or locally advanced gastric or oesogastric junction adenocarcinoma, regardless of HER2 status. The trial did not involve a vulnerable population. Participants were selected based on documented progression on first-line chemotherapy or within specific time frames following the last cycle of certain chemotherapy regimens. They were also required to have an estimated life expectancy of more than three months and adequate haematological, renal, and hepatic function. The sponsor did not provide information on the total number of participants. Lifestyle considerations such as diet and physical activity were not specified. The trial aimed to assess the 6-month overall survival and 4-month quality of life of ramucirumab alone or in combination with paclitaxel.
Plans and Procedures
The clinical trial is a **randomized**, phase II study designed to evaluate the efficacy of **ramucirumab** alone or in combination with **paclitaxel** in older patients with advanced **stomach cancer stage IV with metastases**. The primary objective is to assess the 6-month overall survival and 4-month quality of life. The trial is structured as a double-blind, controlled study to ensure unbiased results. The estimated duration of the trial is from November 16, 2018, to July 31, 2025, with a maximum treatment period of 12 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically proven unresectable metastatic or locally advanced gastric or oesogastric junction adenocarcinoma, age of 70 years or older, and adequate organ function. Following randomization, participants will receive intravenous infusions of the study drugs, with follow-up visits scheduled to monitor treatment response and adverse events. The end-of-study visit will evaluate the primary and secondary endpoints, including survival rates, quality of life, and observed toxicities.
The expected length of participant involvement is up to 12 months, with conditions for early termination including disease progression, unacceptable toxicity, or withdrawal of consent. Secondary endpoints will be assessed, such as dose intensity, time to deterioration in autonomy and quality of life, overall survival, time to treatment failure, and progression-free survival. The trial will also evaluate geriatric parameters every two months. Participants will be censored at the date of last assessment or death if they do not experience deterioration or treatment failure.
Treatment
The clinical trial involves the administration of **Cyramza** (ramucirumab), a **concentrate for solution for infusion**. This experimental medication is provided at a concentration of 10 mg/ml and is administered via **intravenous use**. The dosing regimen specifies a maximum daily dose of 8 mg/kg, with a total treatment period not exceeding 12 weeks. Ramucirumab is a protein-based therapeutic agent, specifically classified under the ATC code L01XC21. The product is manufactured by ELI LILLY NEDERLAND B.V. and is authorized for use in the European Union under the marketing authorization number EU/1/14/957/003.
In addition to ramucirumab, the trial also includes the administration of **PACLITAXEL AHCL**, a **solution for infusion** with a concentration of 6 mg/ml. This non-experimental treatment is also administered intravenously, with a maximum daily dose of 80 mg/m². The treatment duration is similarly capped at 12 weeks. Paclitaxel is a chemically derived active substance, categorized under the ATC code L01CD01. The product is produced by ACCORD HEALTHCARE FRANCE SAS and holds the marketing authorization number 34009 578 808 5 9 in France.
Both treatments are administered in accordance with the trial protocol, ensuring adherence to the specified dosing schedules. Participant compliance is monitored throughout the study to ensure the integrity of the trial data. The primary objective of the trial is to evaluate the 6-month overall survival and 4-month quality of life in patients receiving ramucirumab alone or in combination with paclitaxel, specifically targeting older patients with advanced gastric cancer.
Efficacy
The efficacy of the clinical trial titled "PRODIGE 55-SOCRATE: A randomized phase II study to evaluate second-line **ramucirumab** alone or with **paclitaxel** in older patients with advanced gastric cancer" will be assessed using several primary and secondary endpoints. The primary endpoints include the six-month overall survival rate and quality of life at four months. These will be measured using validated tools such as the EORTC QLQ-C30 and QLQ-ELD-14 questionnaires, which are designed to evaluate the quality of life in cancer patients.
Secondary endpoints will include the description of observed toxicities graded according to NCI-CTC V4, dose intensity assessment, time to deterioration in autonomy, time to deterioration of quality of life scores, overall survival, time to treatment failure, progression-free survival, and evaluation of geriatric parameters every two months. The time to deterioration in autonomy will be determined by the IADL score, while the time to deterioration of quality of life scores will be based on a 10-point decrease in EORTC QLQ-C30 and ELD-14 scores from baseline. Overall survival will be calculated from the date of randomization to the date of death from any cause, with patients lost to follow-up or alive at the time of analysis being censored at the date of last news.
Progression-free survival will be defined as the time from randomization to the first clinical and/or radiological progression or death from any cause, with patients alive without progression being censored at the date of last news. Time to treatment failure will be measured from randomization to treatment failure, progression, treatment discontinuation, or death, with patients without treatment discontinuation being censored at the date of last treatment administration. These efficacy parameters will be collected and analyzed at specified intervals throughout the trial to ensure comprehensive assessment of the treatment's impact on the patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Histologically proven unresectable metastatic or locally advanced gastric or oesogastric junction adenocarcinoma, regardless of HER2 status
- Patient ≥ 70 years
- Estimated life expectancy > 3 months
- Measurable or non-measurable disease according to RECIST 1.1 criteria
- Documented progression on first-line chemotherapy or within 4 months of the last cycle of fluoropyrimidine- and platinum-salt-based or irinotecan-based (with or without anthracycline) chemotherapy for metastatic or locally advanced disease, or within 6 months of the last dose of fluoropyrimidine- and platinum-salt-based adjuvant therapy (immunotherapy is permitted).
- Adequate haematological, renal and hepatic function
- QLQ-C30 and QLQ-ELD-14
- Questionnaire gériatrique IADL
- Signed informed consent
Exclusion Criteria
- Known brain metastasis
- Previous treatment with taxanes
- Previous treatment with an antiangiogenic agent
- Neuropathy grade ≥ 2 (NCI-CTCAE 4.0)
- Unresolved intestinal obstruction or sub-occlusion or inflammatory bowel disease (Crohn's, ulcerative colitis, etc.) or extensive bowel resection associated with chronic diarrhoea.
- Digestive perforation and/or fistula in the 6 months prior to randomisation
- Grade ≥ 3 digestive bleeding less than 3 months old
- Chronic use of antiplatelet drugs, non-steroidal anti-inflammatory drugs, dipyridamole or clopidogrel or similar agents
- Any arterial thromboembolic event in the 6 months prior to randomisation.
- History of life-threatening pulmonary embolism in the 6 months prior to randomisation
- Deep vein thrombosis or pulmonary embolism, or any other significant thrombosis in the 3 months preceding the start of protocol treatment
- Uncompensated congestive heart failure or uncontrolled arrhythmia
- Uncontrolled arterial hypertension despite properly observed antihypertensive treatment
- Child-Pugh B or C cirrhosis, or cirrhosis resulting from cirrhosis.
- Serious or unhealed wound or peptic ulcer or fracture within 28 days prior to randomisation
- Radiotherapy or major surgery within 28 days prior to commencement of protocol treatment, or minor surgery/implantable chamber insertion within 7 days prior to commencement of protocol treatment.
- Known allergy to paclitaxel or ramucirumab
- Other concomitant cancer or history of cancer within 5 years,
- Lack of effective contraception in patients and/or their partners until at least 6 months after the end of treatment with paclitaxel.
- Person under guardianship, curatorship, safeguard of justice or person deprived of liberty
- Unable to undergo medical monitoring of the trial for geographical, social or psychological reasons.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 16 Nov 2018 | 112 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Cyramza 10 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 8 | 12 | PRD1970752 |
PACLITAXEL AHCL 6 mg/ml, solution à diluer pour perfusion | Test | SOLUTION À DILUER POUR PERFUSION | INTRAVENOUS USE | 80 | 12 | PRD4609804 |