Study of Oxaliplatin and Sorafenib Combination to Treat Gastric Cancer Relapsed After a Cisplatin Based Treatment

NCT01262482 | Completed Phase 2

• 2 other identifiers: GEMCAD-08022008-004223-27
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (Relapsed After a Cisplatin Based Treatment)

Keywords

adenocarcinoma; gastric; gastroesophageal junction; Relapsed; sorafenib; oxaliplatin

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Measurements according to RECIST criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan and Magnetic Resonance Imaging (MRI)

  anticipated 3 years

Secondary Outcomes (4)

• Tumoral response

  anticipated 3 years

• Response duration

  anticipated 3 years

• Overall survival

  anticipated 3 years

• Toxicity

  anticipated 3 years

Study Arms (1)

Oxaliplatin + Sorafenib

EXPERIMENTAL

Drug: Oxaliplatin; Drug: Sorafenib

Interventions

Oxaliplatin DRUG

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.

Oxaliplatin + Sorafenib

Sorafenib DRUG

400mg, orally, 2 times per day. Until progression, intolerance or unacceptable toxicity develops, or until patient or investigator decide to stop the treatment.

Oxaliplatin + Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Grupo Espanol Multidisciplinario del Cancer Digestivo: lead

Study Sites (10)

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Sant Pau

Barcelona, Spain

Location

H. Josep Trueta

Girona, Spain

Location

Centro Oncológico M.D. Anderson Spain

Madrid, Spain

Location

Hospital de Fuenlabrada

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Althaia

Manresa, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Spain

Location

Hospital Parc Taulí

Sabadell, Spain

Location

Hospital General de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Adenocarcinoma; Recurrence

Interventions

Oxaliplatin; Sorafenib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Marta Martin Richard, MD

  Grupo Espanol Multidisciplinario del Cancer Digestivo

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: December 17, 2010
• Study Start: October 1, 2008
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 9, 2012

Record last verified: 2010-12

Locations

ES (10)