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

NCT ID: NCT01262482

Last Updated: 2012-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2011-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oxaliplatin + Sorafenib

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: 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.

Sorafenib

Intervention Type: DRUG

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

Interventions

Oxaliplatin

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.

Intervention Type: DRUG

Sorafenib

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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)

2. Older than 18 years at the moment of informed consent form signature

3. Age > 18 years

4. ECOG 0-2

5. Measurable disease by RECIST criteria. Lesions have to be measured by CT-scan or MRI

6. Life expectancy > 12 weeks

7. Adequate medullary reserve and hepatic and renal function, defined according to the following parameters:

1. Hemoglobin ≥ 9g/dl

2. Neutrophils ≥ 1,5 x 10^9/L

3. Platelets ≥100 x 10^9/L

4. Total bilirubin ≤ 1,5 times the upper limit of normal (ULN)

5. ALT (GTP) and AST (GOT) ≤ 2,5 times the upper limit of normal (ULN) (≤ 5 times the ULN in patients with hepatic metastasis)

6. 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)

7. Creatinine clearance > 30ml/min

8. 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

1. More than one line for the treatment of locally advanced disease

2. Active ischemic cardiopathy. History of cardiac disease defined as follow:

1. Congestive cardiac failure > class 2 from the NYHA

2. Active coronary disease. The recruitment of patients with solved myocardial infarction is allowed, if diagnosed at least 6 months before the trial start

3. Cardiac arrhythmia requiring treatment with antiarrhythmic drugs. (The treatment with beta-adrenergic antagonists or digoxin is allowed)

4. Non-controlled arterial hypertension

3. Non-controlled intercurrent illness

4. Symptomatic sensitive peripheral neuropathy

5. 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

6. 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

7. Chronic diseases: AIDS, Hepatitis B and/or Hepatitis C

8. Clinically active severe infection (Grade 2 NCI-CTC version 3.0)

9. Cerebral metastasis or meningeal tumor

10. Patients requiring chronic corticosteroid treatment or high doses of corticosteroids or any other immunosuppressive treatment

11. Patients having undergone a major surgery within the 4 weeks prior to the trial start

12. 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)

13. Previous treatment using a RAS pathway inhibitor

14. 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

15. Patients unable to swallow medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Espanol Multidisciplinario del Cancer Digestivo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marta Martin Richard, MD

Role: STUDY_CHAIR

Grupo Espanol Multidisciplinario del Cancer Digestivo

Locations

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Sant Pau

Barcelona, , Spain

H. Josep Trueta

Girona, , Spain

Centro Oncológico M.D. Anderson Spain

Madrid, , Spain

Hospital de Fuenlabrada

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Althaia

Manresa, , Spain

Clínica Universitaria de Navarra

Pamplona, , Spain

Hospital Parc Taulí

Sabadell, , Spain

Hospital General de Valencia

Valencia, , Spain

Countries

Spain

Other Identifiers

2008-004223-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEMCAD-0802

Identifier Type: -

Identifier Source: org_study_id