Primary: Progression free survival.Secondary: Toxicity, overall survival, response rate, duration of response, translational research.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival.
Secondary outcome
Toxicity, overall survival, response rate, duration of response, translational
research.
Background summary
It is estimated that in the Netherlands each year approximately 900 patients
with gastric cancer or adenocarcinoma of the gastro-oesophageal junction are
candidates for chemotherapy. Randomized studies comparing chemotherapy versus
best supportive care have shown that survival and quality of life are prolonged
with chemotherapy. However, no chemotherapy regimen is clearly superior with
regard to prolongation of survival. Therefore, tolerability of treatment and
ease of administration (outpatient compared to inpatient) are important
considerations for the development of novel treatment schedules.
This is an open-label, multicentre, phase II trial designed to evaluate the
efficacy and safety of bevacizumab in combination with docetaxel, oxaliplatin
and capecitabine chemotherapy (B-DOC) as first-line therapy in patients with
inoperable locally advanced or recurrent and/or metastatic adenocarcinoma of
the stomach or gastro-oesophageal junction. In case of HER2 positive inoperable
locally advanced or recurrent and/or metastatic adenocarcinoma of the stomach
or gastro-oesophageal junction trastuzumab is added to this regimen (B-DOCT).
Stabdard treatment in the Netherlands consists in most clinics of epirubicin,
capecitabine and oxaliplatin or cisplatin.
Study objective
Primary: Progression free survival.
Secondary: Toxicity, overall survival, response rate, duration of response,
translational research.
Study design
National multicenter open non-comparative fase II study.
Treatment:
Cycles of 3 weeks with
• Docetaxel 50 mg/m2 i.v. day 1, max. 6 cycles
• Oxaliplatin 100 mg/m2 i.v. day 1, max. 6 cycles
• Bevacizumab 7.5 mg/kg i.v. day 1, until progression
• Capecitabine 850 mg/m2 (after 6 cycles 1000 mg/m2) orally bid, day 1-14,
until progression.
In case of HER2 positivity of the de tumor, addition of
• Trastuzumab 6 mg/kg i.v. day 1 (at 1st administration 8 mg/kg) , until
progression.
Duration of administration: oxaliplatin plus docetaxel 4 h, bevacizumab 1st
administration * h and thereafter * h, trastuzumab 1st administration 1* h and
thereafter * h.
90 patients.
Intervention
Treatment with docetaxel, oxaliplatin, capecitabine, bevacizumab and, in case
of HER2 positivity also trastuzumab.
Study burden and risks
Risk: AEs of the (combination of the) study drugs.
Burden: The burden for the patient will not be notably different from the
burden during regular treatment. Only the translational research (4 blood
samples during cycle 1-3 and one further sample every following cycle, during
progression, combined with regular blood samples -if possible-) is a clear
additional burden.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
1. Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease not amenable to curative therapy.
2. Measurable/evaluable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST), assessed using imaging techniques (CT or MRI)
3. ECOG Performance status 0, 1 or 2
4. Life expectancy of at least 3 months
5. Male or female age >= 18 years
6. Assessment of HER2 status (primary tumour or metastasis) by the central laboratory prior to initiation of study treatment (Dual SISH, Ventana).
7. LVEF >= 50% assessed by multigated radionucleotide angiography (MUGA) or cardiac ultrasound.
Exclusion criteria
1. Previous chemotherapy for advanced/metastatic disease (prior peri-operative chemotherapy is allowed if at least 6 months has elapsed between completion of this therapy and enrolment into the study)
2. Patients with increased risk of gastro-intestinal perforation in response to treatment due to deep ulceration of the tumour through the wall of the distal oesophagus and/or stomach, as assessed by endoscopy.
3. Previous radiotherapy on the abdomen
4. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma
5. Patients with active (significant or uncontrolled) gastrointestinal bleeding
6. Residual relevant toxicity resulting from previous therapy (with the exception of alopecia), e.g. neurological toxicity >= grade 2 NCI-CTCAE
7. Creatinin clearance <50 mL/min
8. Neutrophil count <1.5 × 109/L, or platelet count <100 × 109/L
9. Serum bilirubin >1.5 × upper limit of normal (ULN); or, AST or ALT >2.5 × ULN (or > 5 × ULN in patients with liver metastases); or, alkaline phosphatase >2.5 × ULN (or >5 × ULN in patients with liver metastases, or >10 × ULN in patients with bone but no liver metastases); or, albumin <25 g/L
10. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
11. History of documented congestive heart failure; angina pectoris requiring medication; evidence of transmural myocardial infarction; poorly controlled hypertension (systolic BP >180 mmHg or diastolic BP >100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias.
12. Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy.
13. Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed)
14. Major surgery within 4 weeks of start of study treatment,
15. Known hypersensitivity to any of the study drugs
16. History or clinical evidence of brain metastases
17. Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes
18. Positive serum pregnancy test in women with childbearing potential
19. Subjects with reproductive potential not willing to use an effective method of contraception
20. Any investigational drug treatment within 4 weeks of start of study treatment
21. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastastic site peripherally and patient recovered from any acute toxicity)
22. Therapeutic use of oral coumarin-derived or LMWH anticoagulants or NSAIDs.
23. Continuous use of immunosuppressive agents (for the use of corticosteroids see #12).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov. NCT01359397 |
| EudraCT | EUCTR2010-022699-30-NL |
| CCMO | NL33964.031.10 |