The primary aim of the study is to investigate whether it is possible to select patients by PET in a good prognosis group (i.e. low SUV) who will not benefit from adjuvant chemotherapy.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Recurrence-free survival.
Secondary outcome
Secondary end-points are overall survival, dose intensity of subsequent cycles,
quality of life, toxicity, health economics. Exploratory endpoints are analysis
of blood and tumor samples for prognostic markers, genomics/proteomics.
Background summary
The use of adjuvant chemotherapy and especially cisplatin in combination
therapy in patients with completely resected early-stage NSCLC improves
disease-free and overall survival. Subgroup analyses suggested that not all
patients benefit from chemotherapy, but how to select patients for treatment is
still not clear. In this study we select patients by FDG-PET in a good
prognosis group using FDG avidity as measured by the standardized uptake value
(SUV). The hypothesis of this study is that in patients with resected NSCLC and
low SUV will not benefit from adjuvant chemotherapy.
Study objective
The primary aim of the study is to investigate whether it is possible to select
patients by PET in a good prognosis group (i.e. low SUV) who will not benefit
from adjuvant chemotherapy.
Study design
This is a randomized multicenter phase III study. Patient with a low SUV of the
primary tumor prior to surgery will be randomised to four cycles of
cisplatin-based chemotherapy or observation in a non-inferiority design. A
total of 864 patients will be entered in the study (432 patients in each arm)
in 4 years. The follow up will continue for 5 years further, at the end of
which a total of 150 events would be observed allowing the comparison
(alpha=0.05 one-sided log-rank test.) of the curves by treatment arm with 80%
power to test the non-inferiority of no chemotherapy to adjuvant chemotherapy.
Intervention
Patients will be randomized to observation or will be treated with 4 cycles of
one of the four cisplatin-based chemotherapy regimens:
-Docetaxel (75 mg/m2 day 1) and cisplatin (75 mg/m2 day 1) Q 3 weeks
-Gemcitabine (1250 mg/m2 day 1 and 8) and cisplatin (75 mg/m2 day 1) Q 3 weeks
-Pemetrexed (500 mg/m2 day 1) and cisplatin (75 mg/m2 day 1) Q 3 weeks
-Vinorelbine (25 mg/m2 day 1 and day 8) and cisplatin (75 mg/m2) day 1 Q 3
weeks
Study burden and risks
Standard treatment of these patients consists of cisplatin based adjuvant
chemotherapy. The hypothesis that patients in the good prognostic group will
have no survival benefit of adjuvant chemotherapy. The experimental arm is no
chemotherapy. Follow-up of the patients will be performed according to the
national guidelines.
Hanzeplein 1
9713 GZ Groningen
NL
Hanzeplein 1
9713 GZ Groningen
NL
Listed location countries
Age
Inclusion criteria
- Age >= 18 years
- Patients with resectable NSCLC
- SUVmax < 10
- Performance score <= 2 before chemotherapy.
- Adequate organ function before administration of chemotherapy, including:
Adequate bone marrow reserve: ANC >= 1.5 x 109/L, platelets >= 100 x 109/L.
Hepatic: bilirubin <= 1.5 x ULN, AP, ALT, AST <= 3.0 x ULN.
Renal: calculated creatinine clearance >= 60 ml/min based on the Cockroft and Gault formula.
- Patients must sign and date a written Independent Ethics Committee approved informed consent form.
Exclusion criteria
- Patients with wedge or segmental resection.
- Patients with stage IA NSCLC
- Prior chemotherapy or radical radiotherapy for NSCLC.
- Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease).
- Concomitant treatment with any other experimental drug under investigation.
- History of any active malignancy (other than NSCLC) unless treated more than 3 years with curative intent and no recurrence, except non-melanoma skin cancer or in situ cervical cancer.
- Pregnancy
- Women of child-bearing potential not using effective means of contraception
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 |
|---|---|
| EudraCT | EUCTR2007-002644-21-NL |
| CCMO | NL17134.042.07 |