Determine wether or not a strategy based on molecular analysis is effective in improving the PFS
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
oncologische aandoening
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival
Secondary outcome
Objective respons rate, Tolerance, Overall survival
Background summary
GEFCAPI 01 randomized phase II trial was conducted from 1999 to 2001 and
demonstrated that the combination of cisplatin and gemcitabine (40 patients)
results in a promising antitumor activity (response rate: 55%, median survival:
8 months) and a favorable pattern of tolerance in patients with CUPs (Culine, J
Clin Oncol 2003). Based on these data, the randomized GEFCAPI 02 trial was
conducted from 2004 to 2007 and tested cisplatin with or without gemcitabine in
patients with CUP and a non-unfavorable prognosis. A median survival rate of 11
months was obtained in the combination arm (27 patients), as compared to 8
months in the single arm (25 patients) (Gross-Goupil 2008). Taken together,
results from the GEFCAPI 01 and 02 trials indicate that the
cisplatin-gemcitabine association is a reasonable empiric chemotherapy regimen
in patients with CUPs.
In recent years, several groups have shown that cancers can be identified with
a high reproducibility by their microarray signature. In the meantime,
important therapeutic progresses have been made in a number of metastatic
cancers using specific treatments (chemotherapy and/or targeted agents),
leading to improvement in progression-free survival and in some cases, overall
survival.
Therefore, it becomes more tempting to identify a primary cancer before
treating a patient with CUP, so that a more specific treatment can be used.
In an effort to develop such a strategy, the GEFCAPI embarked in 2008 in a
feasibility study in which RNA was extracted from tissue samples of 20 patients
with CUP and a microarray analysis was performed to compare their gene
expression with that of known primary cancer signatures (Gross-Goupil 2008).
The results indicated that:
a clinically acceptable delay (median: 10 days) could be achieved between
tissue sample shifting and receipt of the molecular analysis by the
investigator, making this strategy feasible in practice;
almost half of the primary cancers suspected by microarray analysis
(colo-rectal cancer, hepatocarcinoma, renal cell carcinoma, breast cancer,
melanoma) would not be treated appropriately by an empiric chemotherapy regimen
like the cisplatin-gemcitabine combination.
This clearly supports the study of gene microarray analysis followed by
suspected primary cancer-tailored specific therapy in patients with CUP
Study objective
Determine wether or not a strategy based on molecular analysis is effective in
improving the PFS
Study design
European randomised phase III multi centric study comparing a diagnostic and
therapeutic strategy based on molecular analysis followed by suspected primary
cancer tailored specific therapy to an empiric strategy in patients with
carcinoma of unknown primary.
Intervention
Molecular analysis test
Study burden and risks
No additional risk for the patient. The moleculary analysis will be performed
on the sample that has been done for standard of care.
Tegelseweg 2 210
Venlo 5912 BL
NL
Tegelseweg 2 210
Venlo 5912 BL
NL
Listed location countries
Age
Inclusion criteria
1) Patients presenting with carcinoma of an unknown primary, confirmed by histo-pathological analysis (including an immunohistochemical analysis) and corresponding to one of the following histologic types: moderately or welldifferentiated adenocarcinoma, poorly-differentiated adenocarcinoma, undifferentiated carcinoma, squamous-cell carcinoma
2) Diagnostic work-up in keeping with Standard Options Recommandations des CAPI (Lesimple et al., 2003),
3) Age>18 years,
4) Performance status 0, 1 or 2 according to ECOG
5) Good or poor prognosis CUP classified according to the GEFCAPI classification
6) CUP with at least one measurable lesion
7) Tumour sample available for molecular analysis.
8) CUP not belonging to a subgroup requiring a specific treatment,
9) Satisfactory haematological, renal and hepatic function
10) Cardiac, respiratory and neurological function compatible with the administration of cisplatin chemotherapy,
11) No previous chemotherapy for CUP,
12) Previous radiotherapy is acceptable, but it should be completed at least 4 weeks before the start of systemic treatment. Randomisation can be performed during this time frame,
13) All patients with reproductive potential must practice an effective method of birth control throughout the study. Female patients with childbearing potential must have a negative pregnancy test within 7 days before study treatment
14) Information delivered to patient and informed consent form signed by the patient or legal representative.
Exclusion criteria
1) Patients in whom the diagnosis has not been histologically confirmed (a cytological analysis alone does not permit patient entry onto the trial),
2) Patients with known HIV infection
3) Patients with symptomatic brain metastases,
4) Associated disease likely to prevent the patient from receiving the treatment,
5) Previous history of cancer (excepted skin basocellular epithelioma or epithelioma in situ of the uterine cervix) during the 5 years before study entry,
6) Patients already included in another clinical trial with an experimental therapy,
7) Pregnant women, and women who are breastfeeding,
8) Compliance with trial medical follow-up impossible due to geographic, social or psychological reasons.
Design
Recruitment
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 | 2011-A01202-39 |
| CCMO | NL40415.068.12 |