The primary aim of the study is to investigate whether adding Nadroparin to adjuvant chemotherapy in patients in the poor prognostic group (i.e. high SUV) prolongs recurrence-free survival.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint is recurrence-free survival.
Secondary outcome
Secundary 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
recurrence-free and overall survival. In this study we combine cisplatin with a
potent and least toxic drug pemetrexed. 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 and a poor prognosis group using FDG avidity as measured by the
standardized uptake value (SUV). Several studies suggested that treatment with
low-molecular weight heparin (LMWH) improves survival in cancer patients. The
hypothesis of this study is that in patients with resected NSCLC and high SUV
(poor prognosis group) adding LMWH to four cycles of adjuvant chemotherapy will
improve the recurrence-free survival rate.
Study objective
The primary aim of the study is to investigate whether adding Nadroparin to
adjuvant chemotherapy in patients in the poor prognostic group (i.e. high SUV)
prolongs recurrence-free survival.
Study design
This is a randomized multicenter phase III study. Patient with a high SUVof the
primary tumor prior to surgery will be randomised to four cycles of pemetrexed
and cisplatin with or without nadroparin for 16 weeks in order to improve the
recurrence-free survival rate in these patients. A total of 600 patients will
be entered in the study (300 patients in each arm) in 3 years. The follow up
will continue for 2 years and 3 months further, at the end of which a total of
243 events would be observed allowing the comparison (alpha=0.05 two-sided
log-rank test.) of the curves by treatment arm with 80% power to detect a true
difference of 60% versus 70% at 3 years, or HR=0.70.
Intervention
Within 4-6 weeks after surgery all patients will receive 4 cycles of pemetrexed
(500 mg/m2) and cisplatin (75 mg/m2) on day 1 every 3 weeks. Patients in de
nadroparin arm will receive nadroparin s.c. daily for 16 weeks, 2 weeks
therapeutic dose en 14 weeks half-therapeutic dose.
Study burden and risks
Treatment of these patients consists of cisplatin based adjuvant chemotherapy
for 4 cycles. After treatment the follow-up of patients will be every 8 weeks
for the first 2 years and thereafter every 3 months till 5 years after surgery.
Patients in the nadroparin arm will receive nadroparin s.c. daily for 16 weeks.
No additional toxicity is expected. The duration of the treatment is 16 weeks
and the duration of the study is about 5 years.
Hanzeplein 1
9713 GZ Groningen
NL
Hanzeplein 1
9713 GZ Groningen
NL
Listed location countries
Age
Inclusion criteria
- Patients with resectable NSCLC
- SUVmax >= 10
- Age >= 18 years
- WHO 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.
INR < 1.5
- Patients must sign and date a written Independent Ethics Committee approved informed consent form.
Exclusion criteria
- 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.
- Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8 day period for long-acting agents such as piroxicam).
- Inability or unwillingness to take folic acid, vitamin B-12 supplementation or dexamethasone.
- 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
- Men and women of child-bearing potential not using effective means of contraception for 6 months after treatment has been completed
- Indication for anticoagulant treatment.
- Any contraindication listed in the labeling of nadroparin.
- Documented history of heparin-induced thrombocytopenia with UFH or LMWH
- Current active bleeding or judged to be as high risk of bleeding;
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 | EUCTR2007-002608-16-NL |
| CCMO | NL16517.042.07 |