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JOURNAL ONKOLOGIE – STUDIE
RAMIRIS

Ramucirumab Plus FOLFIRI Versus Ramucirumab Plus Paclitaxel in Patients With Advanced or Metastatic Gastric Cancer, Who Failed One Prior Line of Palliative Chemotherapy

Rekrutierend

NCT-Nummer:
NCT03081143

Studienbeginn:
Mai 2017

Letztes Update:
07.03.2024

Wirkstoff:
FOLFIRI, Ramucirumab, Paclitaxel

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Collaborator:
-

Studienleiter

Salah-Eddin Al-Batran, Prof
Study Chair
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Kontakt

Studienlocations
(3 von 16)

Ordensklinikum Linz GmbH, Barmherzige Schwestern
4010 Linz
AustriaRekrutierend» Google-Maps
Landeskrankenhaus Feldkirch - Rankweil
6830 Rankweil
AustriaRekrutierend» Google-Maps
Wiener Neustadt, Landesklinikum
2700 Wiener Neustadt
AustriaRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This clinical trial will evaluate whether it is beneficial in terms of prolongation of

survival to combine FOLFIRI (standard treatment) with ramucirumab compared to the standard

treatment of ramucirumab plus paclitaxel in patients with advanced gastric cancer after

failure of one prior line of palliative chemotherapy. This trial aims to investigate the

efficacy and safety of ramucirumab plus FOLFIRI (investigational arm A) compared to

paclitaxel plus ramucirumab (control arm B).

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Signed written informed consent

2. Male or female* ≥ 18 years of age; Patients in reproductive age must be willing to use

adequate contraception (that results in a failure rate of <1% per year) during the

study and for 3 months after the end of ramucirumab treatment (appropriate

contraception is defined as surgical sterilization (e.g. bilateral tubal ligation,

vasectomy), hormonal contraception (including oral contraceptive pills (combination of

estrogen and progesterone), vaginal ring, injectables, implants, intrauterine devices

(IUDs) and intrauterine hormone-releasing system (IUS)), nonhormonal IUDs and complete

abstinence). Female patients with childbearing potential need to have a negative

pregnancy test within 7 days before study start.

3. Histologically proven gastric adenocarcinoma including adenocarcinoma of the

esophagogastric junction

4. Metastatic or locally advanced disease, not amenable to potentially curative resection

5. Phase II only: Documented objective radiological or clinical disease progression

during or within 6 months of the last dose of first-line platinum and fluoropyrimidine

doublet with or without anthracycline or docetaxel. Neoadjuvant/adjuvant treatment is

not counted unless progression occurs <6 months after completion of the treatment. In

these cases neoadjuvant/adjuvant treatment is counted as one line.

OR Phase III only: Radiological or clinical disease progression during or after the

last dose of a first-line platinum, fluoropyrimidine-containing therapy. Patients must

also have received a taxane with the first-line or during their adjuvant or

neoadjuvant therapy or both. Neoadjuvant/adjuvant platinum containing therapy is

permitted and is counted as first-line therapy if progression occurs <12 months after

completion of the treatment. If progression occurred ≥ 12 months after completion of

neoadjuvant/adjuvant therapy, the therapy is not counted as a treatment line. At

decision of the investigator, different regimens can be considered as one line of

prior treatment, in case these were administrated as a sequential or alternating

therapy.

6. Measurable or non-measurable but evaluable disease

7. ECOG performance status 0-1

8. Life expectancy > 12 weeks

9. Adequate hematological, hepatic and renal functions:

- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

- Platelets ≥ 100 x 10^9/L

- Hemoglobin ≥9 g/dL (5.58 mmol/L)

- Total bilirubin ≤ 1.5 times the upper normal limit (UNL)

- AST (SGOT) and ALT (SGPT) ≤ 2.5 x UNL in absence of liver metastases, or ≤ 5 x

UNL in presence of liver metastases; AP ≤ 5 x UNL

- Serum creatinine ≤ 1.5 x upper limit of normal, or creatinine clearance (measured

via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5

times the ULN, a 24-hour urine collection to calculate creatinine clearance must

be performed)

- Urinary protein ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or

routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate

<1000 mg of protein in 24 hours to allow participation in this protocol)

- Adequate coagulation function as defined by International Normalized Ratio (INR)

≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless

receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon

must be switched to low molecular weight heparin and have achieved stable

coagulation profile prior to first dose of protocol therapy.

10. Ability to comply with scheduled assessments and with management of toxicities

Exclusion Criteria:

1. Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second

cancer except in patients with squamous or basal cell carcinoma of the skin or

carcinoma in situ of the cervix that has been effectively treated. Patients curatively

treated and disease-free for at least 5 years will be discussed with the sponsor

before inclusion

2. Squamous gastric cancer

3. Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not

indicated in the study protocol

4. Phase II only: Previous therapy with paclitaxel or FOLFIRI Phase III only: Previous

therapy with FOLFIRI

5. Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment

start unless rapidly progressing disease is measured

6. Concurrent treatment with any other anti-cancer therapy

7. Previous exposure to a VEGF or VEGFR inhibitor or any antiangiogenic agent, or prior

enrolment in this study

8. Patient has undergone major surgery within 28 days prior to first dose of protocol

therapy, or minor surgery/subcutaneous venous access device placement within 7 days

prior to first dose of protocol therapy. The patient has elective or planned major

surgery to be performed during the course of the clinical trial

9. Grade 3-4 GI bleeding within 3 months prior to enrollment

10. History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other

significant thromboembolism (venous port or catheter thrombosis or superficial venous

thrombosis are not considered "significant") during the 3 months prior to first dose

of protocol therapy

11. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a

history of hepatic encephalopathy or clinically meaningful ascites resulting from

cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis

requiring diuretics or paracentesis.

12. The patient has uncontrolled known brain or leptomeningeal metastases

13. Known allergic/ hypersensitivity reaction to any of the components of the treatment

14. Contraindications to the use of atropine

15. Other serious illness or medical conditions within the last 12 months prior to study

drug administration

16. Any arterial thromboembolic events, including but not limited to myocardial

infarction, transient ischemic attack, cerebrovascular accident, or unstable angina,

within 6 months prior to first dose of protocol

17. The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or

> 100 mmHg diastolic for >4 weeks) despite standard medical management

18. Active uncontrolled infection

19. Current history of chronic diarrhea

20. Active disseminated intravascular coagulation

21. Any other serious concomitant disease or medical condition that in the judgment of the

investigator renders the subject at high risk of treatment complication or reduced the

probability of assessing clinical effect

22. Known Dihydropyrimidine dehydrogenase (DPD) deficiency

23. Prior history of GI perforation/fistula (within 6 months of first dose of protocol

therapy) or risk factors for perforation.

24. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first

dose of protocol therapy

25. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal

anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others),

dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose

325 mg/day) is permitted

26. Concurrent treatment with other experimental drugs or participation in another

clinical trial with any investigational drug within 30 days prior to treatment start

or at the same time as this study

27. Lack of resolution of all toxic effects (excluding alopecia) of prior chemotherapy,

prior radiotherapy or surgical procedure to National Cancer Institute (NCI) Common

Terminology Criteria for Adverse Events (CTCAE) grade < 1. Note: Neuropathy due to

prior chemotherapy is allowed if not > NCI Grade II according to CTCAE version 4.03

28. Subject pregnant or breast feeding, or planning to become pregnant within 3 months

after the end of treatment

29. Subject (male or female) is not willing to use highly effective methods of

contraception (per institutional standardCTFG-Guideline) during treatment and for 3

months (male or female) after the end of treatment

30. Patients known to have a HER 2 positive Cancer who have not been treated already with

a HER 2 targeting agent.

31. Patients with a psychiatric illness or patients imprisoned or working in the

institution of the treating physician.

Studien-Rationale

Primary outcome:

1. OS Rate at 6 months primary endpoint for phase II (Time Frame - 6 months after randomization):
OS Rate at 6 months is defined at the proportion of patients being known to be alive at 6 months after randomisation

2. overall survival (OS) co-primary endpoint for phase III (Time Frame - from date of randomization to 1 year after end of treatment):
duration from date of randomization to death

3. Objective Overall Response Rate (ORR) co-primary endpoint for phase III (Time Frame - from randomization for the time of treatment with a maximum of 1 year):
proportion of patients with complete or partial response (CR + PR) according to RECIST 1.1

Secondary outcome:

1. Progression-free survival (Time Frame - from date of first study drug administration to up to 1 year after study completion):
duration from the first study drug administration to the first documented evidence of disease progression or death

2. Overall response rate (CR + PR) - endpoint for phase II (Time Frame - from randomization for the time of treatment with a maximum of 1 year):
proportion of patients with complete or partial response (CR + PR) according to RECIST 1.1

3. Disease control rate (CR + PR + SD) (Time Frame - from randomization for the time of treatment with a maximum of 1 year):
proportion of patients with complete or partial response or stable disease (CR + PR + SD) according to RECIST 1.1

4. incidence and severity of adverse events according to CTC criteria (Time Frame - from randomization until 30 days after the last dose of study drug):
incidence and severity of adverse events according to CTC criteria

5. Patient reported outcomes: quality of life according to questionnaire EORTC-QLQ-C30 (Time Frame - from randomization until 30 days after the last dose of study drug):
quality of life scores according to validated questionnaire EORTC-QLQ-C30

Studien-Arme

  • Experimental: FOLFIRI plus Ramucirumab
    Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle plus FOLFIRI (Irinotecan 180 mg/m2; i.v. bolus of 5-FU 400 mg/m2, i.v. infusion of leucovorin 400 mg/m2 , followed by a 46-hour continuous administration of 5-FU 2400 mg/m2 on day 1 and 15 of a 28-day cycle)
  • Active Comparator: Paclitaxel plus Ramucirumab
    Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle plus Paclitaxel 80 mg/m2 on day 1, 8, 15

Geprüfte Regime

  • FOLFIRI:
    Irinotecan 180 mg/m2; i.v. bolus of 5-FU 400 mg/m2, i.v. infusion of leucovorin* 400 mg/m2 , followed by a 46-hour continuous administration of 5-FU 2400 mg/m2 on day 1 and 15 of a 28-day cycle
  • Ramucirumab:
    8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle
  • Paclitaxel:
    80 mg/m2 on day 1, 8, 15

Quelle: ClinicalTrials.gov


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