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- Klinische proef NCT01262482
Study of Oxaliplatin and Sorafenib Combination to Treat Gastric Cancer Relapsed After a Cisplatin Based Treatment
A Phase 2 Trial of Oxaliplatin and Sorafenib Combination in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma, Relapsed After a Cisplatin Based Treatment
In Spain, the gastric carcinoma is the 5th most frequent malignant tumor in women and the 6th in men, and represents the 3rd cause of cancer-related deaths amongst women and the 4th amongst men. The average of 5-year survival rate in Spain is under 30%. The main reason of it is that, despite carrying out an adjuvant treatment, more than the 50% will present relapsed disease.
Sorafenib has been the first RAF inhibitor, both of RAF-1 and B-rRAF and its b-RAF variant V600E. Moreover, it has shown its ability to inhibit other tyrosin-quinase receptors as VEGFR 2 and 3, c-kit, Flt-3 or PDGFR. Its activity has been clearly proven in clear cell renal carcinoma.
The mechanism by which Sorafenib seems to act is not because of the existence of a mutation of RAS or RAF, but because as there is a VHL shortage the HIP produces a VEGF, bFGF or TGF overexpression that produces in turn a hyper-stimulation on the RAF/ERK/MEK pathway.
The RAF/MEK/ERK pathway and angiogenesis seem to be clearly involved in the gastric carcinoma tumorigenesis and progression. Because of that, it seems interesting to associate Sorafenib to an oxaliplatin-based chemotherapy, which has shown its effectiveness in relapsed patients after receiving cisplatin-based schemes. Moreover, there is a phase 1 trial confirming the tolerance of the oxaliplatin and Sorafenib association, describing partial responses amongst gastric cancer patients previously treated with cisplatin.
Studie Overzicht
Toestand
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Barcelona, Spanje
- Hospital Clinic de Barcelona
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Barcelona, Spanje
- Hospital Sant Pau
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Girona, Spanje
- H. Josep Trueta
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Madrid, Spanje
- Hospital La Paz
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Madrid, Spanje
- Hospital De Fuenlabrada
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Madrid, Spanje
- Centro Oncológico M.D. Anderson Spain
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Manresa, Spanje
- Hospital Althaia
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Pamplona, Spanje
- Clinica Universitaria de Navarra
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Sabadell, Spanje
- Hospital Parc Tauli
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Valencia, Spanje
- Hospital General de Valencia
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Gastric or gastroesophageal junction adenocarcinoma confirmed by cytology or biopsy, with unresectable or metastatic disease which have progressed to a cisplatin-fluoropyrimidine based scheme (excluded neoadjuvant treatment administered with or without concomitant radiotherapy)
- Older than 18 years at the moment of informed consent form signature
- Age > 18 years
- ECOG 0-2
- Measurable disease by RECIST criteria. Lesions have to be measured by CT-scan or MRI
- Life expectancy > 12 weeks
Adequate medullary reserve and hepatic and renal function, defined according to the following parameters:
- Hemoglobin ≥ 9g/dl
- Neutrophils ≥ 1,5 x 10^9/L
- Platelets ≥100 x 10^9/L
- Total bilirubin ≤ 1,5 times the upper limit of normal (ULN)
- ALT (GTP) and AST (GOT) ≤ 2,5 times the upper limit of normal (ULN) (≤ 5 times the ULN in patients with hepatic metastasis)
- PT-INR-PTT ≤ 1,5 times the ULN. (The patients under anticoagulant treatment with dicumarin or heparin can be included if there is no previous evidence of alteration in these parameters)
- Creatinine clearance > 30ml/min
- The patients have to be able to understand the meaning of their participation in the trial and voluntary give their participation consent signing the informed consent form
Exclusion Criteria:
- More than one line for the treatment of locally advanced disease
Active ischemic cardiopathy. History of cardiac disease defined as follow:
- Congestive cardiac failure > class 2 from the NYHA
- Active coronary disease. The recruitment of patients with solved myocardial infarction is allowed, if diagnosed at least 6 months before the trial start
- Cardiac arrhythmia requiring treatment with antiarrhythmic drugs. (The treatment with beta-adrenergic antagonists or digoxin is allowed)
- Non-controlled arterial hypertension
- Non-controlled intercurrent illness
- Symptomatic sensitive peripheral neuropathy
- Another malignant disease diagnosed in the past 5 years, except in situ cervix carcinoma adequately treated, non-melanoma skin carcinoma, superficial bladder tumor (Ta, Tis and T1), or any tumor treated in a curative way until 3 years prior to the recruitment
- Pregnant or breastfeeding women. Women will have to undergo a pregnancy test within 7 days prior to the recruitment. Both men and women recruited in the trial will have to use appropriate barrier contraceptive methods during their sexual relations during the trial period and at least until two weeks after its completion. Men participating in this trial will have to continue using this contraceptive methods at least until 3 months after the treatment completion
- Chronic diseases: AIDS, Hepatitis B and/or Hepatitis C
- Clinically active severe infection (Grade 2 NCI-CTC version 3.0)
- Cerebral metastasis or meningeal tumor
- Patients requiring chronic corticosteroid treatment or high doses of corticosteroids or any other immunosuppressive treatment
- Patients having undergone a major surgery within the 4 weeks prior to the trial start
- Patients having completed a chemotherapy or radiotherapy treatment within the 4 weeks prior to the clinical trial start (except palliative radiotherapy, within the 2-weeks prior to the clinical trial start)
- Previous treatment using a RAS pathway inhibitor
- Any medical or severe psychiatric condition or drug consumption involving a serious risk for the patient if taking part in the clinical trial or that can prevent the signature of the informed consent form
- Patients unable to swallow medication
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Oxaliplatin + Sorafenib
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130 mg/m2, IV during 2 hours on day 1 of each 21 day cycle.
Number of cycles: until progression, intolerance or unacceptable toxicity develops, or until patient or investigator decide to stop the treatment.
400mg, orally, 2 times per day.
Until progression, intolerance or unacceptable toxicity develops, or until patient or investigator decide to stop the treatment.
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Progression free survival
Tijdsspanne: anticipated 3 years
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Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors).
Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)
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anticipated 3 years
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Tumoral response
Tijdsspanne: anticipated 3 years
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Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors).
Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)
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anticipated 3 years
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Response duration
Tijdsspanne: anticipated 3 years
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Duration of the partial or total response to the treatment.
Evaluation and classification according to RECIST criteria (Response Evaluation Criteria in Solid Tumors)
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anticipated 3 years
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Overall survival
Tijdsspanne: anticipated 3 years
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anticipated 3 years
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|
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Toxicity
Tijdsspanne: anticipated 3 years
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anticipated 3 years
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Medewerkers en onderzoekers
Onderzoekers
- Studie stoel: Marta Martin Richard, MD, Grupo Espanol Multidisciplinario del Cancer Digestivo
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Ziekten van het spijsverteringsstelsel
- Neoplasmata per histologisch type
- Neoplasmata
- Neoplasmata per site
- Carcinoom
- Neoplasmata, glandulair en epitheel
- Gastro-intestinale neoplasmata
- Neoplasmata van het spijsverteringsstelsel
- Gastro-intestinale aandoeningen
- Hoofd- en nekneoplasmata
- Slokdarmaandoeningen
- Adenocarcinoom
- Slokdarmneoplasmata
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Proteïnekinaseremmers
- Sorafenib
- Oxaliplatine
Andere studie-ID-nummers
- GEMCAD-0802
- 2008-004223-27 (EudraCT-nummer)
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