PRODIGE 55-SOCRATE : A randomized phase II study to evaluate second-line ramucirumab alone or with paclitaxel in older patients with advanced gastric cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

10 Jul 2024 → 26 Sep 2025

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513515-27-00

EudraCT number

2017-001683-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective was to assess the 6-month overall survival and 4-month quality of life of ramucirumab alone or in combination with paclitaxel.

Secondary objectives 10

1. Other dimensions of quality of life at 4 months
2. Time to deterioration in health-related quality of life
3. Time to degradation of autonomy
4. Overal survival
5. Toxicity
6. Time to treatment failure
7. Progression-free survival
8. Best tumour response during treatment
9. Geriatric prognostic and predictive factors for the efficacy and tolerability of treatment
10. prognostic and predictive nutritional factors for treatment tolerance

Conditions and MedDRA coding

stomach cancer stage IV with metastases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically proven unresectable metastatic or locally advanced gastric or oesogastric junction adenocarcinoma, regardless of HER2 status
2. Patient ≥ 70 years
3. Estimated life expectancy > 3 months
4. Measurable or non-measurable disease according to RECIST 1.1 criteria
5. 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).
6. Adequate haematological, renal and hepatic function
7. QLQ-C30 and QLQ-ELD-14
8. Questionnaire gériatrique IADL
9. Signed informed consent

Exclusion criteria 21

1. Known brain metastasis
2. Previous treatment with taxanes
3. Previous treatment with an antiangiogenic agent
4. Neuropathy grade ≥ 2 (NCI-CTCAE 4.0)
5. Unresolved intestinal obstruction or sub-occlusion or inflammatory bowel disease (Crohn's, ulcerative colitis, etc.) or extensive bowel resection associated with chronic diarrhoea.
6. Digestive perforation and/or fistula in the 6 months prior to randomisation
7. Grade ≥ 3 digestive bleeding less than 3 months old
8. Chronic use of antiplatelet drugs, non-steroidal anti-inflammatory drugs, dipyridamole or clopidogrel or similar agents
9. Any arterial thromboembolic event in the 6 months prior to randomisation.
10. History of life-threatening pulmonary embolism in the 6 months prior to randomisation
11. Deep vein thrombosis or pulmonary embolism, or any other significant thrombosis in the 3 months preceding the start of protocol treatment
12. Uncompensated congestive heart failure or uncontrolled arrhythmia
13. Uncontrolled arterial hypertension despite properly observed antihypertensive treatment
14. Child-Pugh B or C cirrhosis, or cirrhosis resulting from cirrhosis.
15. Serious or unhealed wound or peptic ulcer or fracture within 28 days prior to randomisation
16. 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.
17. Known allergy to paclitaxel or ramucirumab
18. Other concomitant cancer or history of cancer within 5 years,
19. Lack of effective contraception in patients and/or their partners until at least 6 months after the end of treatment with paclitaxel.
20. Person under guardianship, curatorship, safeguard of justice or person deprived of liberty
21. Unable to undergo medical monitoring of the trial for geographical, social or psychological reasons.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Six months survival rate and quality of life at 4 months

Secondary endpoints 8

1. description of observed toxicities graded according to NCI-CTC V4 and description of SAEs
2. dose intensity will be assessed by the ratio (expressed as a %): actual dose(DR)/theoretical dose(DT) for each chemotherapy product (Ramucirumab or Paclitaxel)
3. The time to deterioration in autonomy was defined as the time between the date of randomisation and the date on which the IADL score decreased by at least 1 point compared with the score calculated at inclusion. Patients who were alive or who died without deterioration in autonomy were censored at the date of the last IADL assessment or at the date of death.
4. Time to deterioration of quality of life scores is defined as the time between the date of randomisation and the date of deterioration of the EORTC QLQC30 and ELD 14 scores by 10 points relative to the score at inclusion. Patients alive or who died without deterioration will be censored at the date of last QoL assessment or at the date of death.
5. Overall survival is defined as the time from the date of randomisation to the date of death from any cause. Patients lost to follow-up or alive at the time of analysis will be censored at the date of last news.
6. Time to treatment failure is defined as the time between the date of randomisation and the date of treatment failure (progression and/or treatment discontinuation or death (whatever the cause). Patients without treatment discontinuation will be censored at the date of last treatment administration.
7. Progression-free survival is defined as the time between the date of randomisation and the date of first clinical and/or radiological progression or death (from any cause). Patients alive without progression will be censored at the date of last news.
8. Evaluation of geriatric parameters (every 2 months)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon Cedex

Postcode

21079

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Astrid LIEVRE

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Manon PELKOWSKI

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications