|- candidate number||1787|
|- NTR Number||NTR470|
|- Date ISRCTN created||27-jan-2006|
|- date ISRCTN requested||18-nov-2005|
|- Date Registered NTR||25-okt-2005|
|- Secondary IDs||N/A |
|- Public Title||Chemotherapy +/- vitamine supplementation in advanced Esophagogastric cancer.|
|- Scientific Title||Randomized Phase 2 study with Gemzar and Cisplatin combination with or without Vitamin Supplementation in patients with advanced Esophagogastric Cancer.|
|- ACRONYM||Vitamine study|
|- hypothesis||Primary objective: |
Does supplementation of vitamins to the combination of gemcitabine and cisplatin increases the response rate in patients with esophagogastric cancer.
To assess the relationship between plasma homocysteine and plasma folic acid concentrations. To assess whether genetic polymorphisms in folate metabolising enzymes are related to folate homeostasis and efficacy.To determine the relationship between response and biomarkers for either gemcitabine and cisplatin.To determine whether vitamin supplementation affects pharmacokinetics of gemcitabine and cisplatin. To assess the time to progressive disease and overall survival.To assess the hematopoietic response of darbepoetin alfa.
|- Healt Condition(s) or Problem(s) studied||Esophagogastric cancer|
|- Inclusion criteria||1. Patients must have histologically or cytological confirmed metastatic or locally advanced unresectable advanced esophagogastric carcinoma (squamous or adenocarcinoma), not amenable for curative treatment. |
2. Patients may have received prior surgery, and chemotherapy and/or radiotherapy in neo-adjuvant or adjuvant setting as long as the chemotherapy was completed at least 6 months prior to study entry.
3. Patients should have measurable disease according to RECIST Criteria.
4. Age of at least 18.
5. Performance status (ECOG) 0, 1 or 2.
6. Life expectancy of at least 12 weeks.
7. Adequate bone marrow function, defined by a neutrophil count above 1.5 x 109/L, platelet count above 100 x 109/L and hemoglobin above 5,6 mmol/L.
8. Adequate renal and hepatic function, defined by bilirubin £ 1.5 x upper limit of normal (ULN), alkaline phosphatase (AP), Aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x ULN (<5 x ULN is acceptable in case of liver metastasis) and creatinine £ 120 ́mol/L and/or creatinine clearence > 60mL/min ( calculated by using the Cockcroft and Gault formula.
9. Patients must not already be taking vitamin supplements as defined in the protocol.
10. Patients with childbearing potential must use an adequate contraceptive method.
11. Patients must be able to comply with protocol procedures, able to swallow pills and have adequate geographical proximity to the study site.
12. Patients must sign written informed consent.
|- Exclusion criteria||1. Active infection or cardiac disease, at the investigator’s criteria. |
2. Pregnancy or breast-feeding.
3. Known symptomatic metastasis in the central nervous system (CNS).
4. Treatment with any investigational agent in the month prior to inclusion.
5. Other serious disease, at the investigator’s discretion.
6. Prior diagnosis of other malignant disease, excluding adequately treated in situ carcinoma of the cervix and skin cancer other than melanoma, low grade prostate carcinoma (gleason score < 6) or any other non-relapsed malignancy that was treated more than five years before diagnosis.
7. Received any RBC transfusions within 14 days before first dose of Aranesp or received rHuEPO or darbepoetin alfa therapy within 4 weeks before study day 1.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mrt-2004|
|- planned closingdate||1-mrt-2006|
|- Target number of participants||82|
|- Interventions||Group A:|
patients will be treated with gemcitabine 1250 mg/m2 IV on days 1 and 8 in combination with Cisplatin 80 mg/m2 on day 1 with vitamin supplementation (Folic acid 450 ́g/24h PO, starting at least one week prior to chemotherapy and finishing at least 3 weeks after the last treatment dose. Vitamin B12 1000́g approximately every 9 weeks, starting 1 week before chemotherapy and finishing at least 3 weeks after the last treatment dose).
patients will be treated with gemcitabine 1250 mg/m2 on days 1 and 8 in combination with Cisplatin 80 mg/m2 on day 1 without vitamin supplementation. Cycles will be administered every 21 days. A maximum of 6 cycles will be administered to every patient, although this number could be increased if the patient may benefit from it, based on investigators criteria.
|- Primary outcome||Response rate.|
|- Secondary outcome||Time to progression, overall survival.|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Dr. N. Groeningen, van|
|- CONTACT for SCIENTIFIC QUERIES||Dr. N. Groeningen, van|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|Amgen, VU University Medical Center, Eli Lilly Nederland B.V.|
|- Brief summary||The combination of gemcitabine and cisplatin has shown modest activity in
patients with advanced/metastatic cancer of the esophagus and stomach.|
Improvements of these treatment results is needed. The present study
investigates whether the addition of folic acid and vitamin B12 to the
treatment with cisplatin and gemcitabine will improve the response rate.
Eighty-two patients will be needed to test the hypothesis that the response
rate will increase from 33% to 50%.
Other aspects that will be addressed in this study are the relationship
between homocysteine and folic acid concentrations, genetic polymorphisms in
folate metabolising enzymes, relationship between biomarkers for both
gemcitabine and cisplatin and response, and pharmacokinetics of cisplatin
and gemcitabine in 10 patients on day 1 of the first cycle.
Time to progression and overall survival time will also be assessed.
|- Main changes (audit trail)|
|- RECORD||25-okt-2005 - 11-nov-2008|