To assess the safety of cisplatin doublets with hypofractionated radiotherapy (24 x2.75Gy).
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the safety of concurrent high dose chemotherapy with hypofractionated
radiotherapy as defined by the rate of grade 5 treatment-related adverse events
that occur during treatment and 3-month follow-up.
Secondary outcome
- The one-year disease control rate.
- Progression free survival
- Overall survival.
Background summary
Concurrent chemoradiotherapy is the standard treatment for locally advanced
non-small cell lung carcinoma (NSCLC). Different chemotherapy and radiation
regimens have been advocated but in general, cisplatin-doublets are deemed
standard of care. Decreasing the overall treatment time of irradiation is
thought to increase the efficacy. Extensive experience is available on the
combination of daily-low dose cisplatin in combination with hypofractionated
radiotherapy. However, no data is available on the safety of cisplatin doublets
and hypofractionated radiotherapy
Study objective
To assess the safety of cisplatin doublets with hypofractionated radiotherapy
(24 x2.75Gy).
Study design
Patients presenting with locally advanced NSCLC will be consented to
participate in this phase 2 trial that evaluates the concurrent treatment of
Cisplatin (Day 1: 75mg/m2) and Pemetrexed (Day 1: 500mg/m2 for non-squamous) or
Etoposide (Day1-3 100mg/m2 for squamous), 3-weekly regimens, together with
radiotherapy (24 daily fractions of 2.42 Gy to the mediastinal lymph nodes
with an integrated boost of 2.75 Gy to the primary tumour). An interim analysis
is planned following the first cohort of 25 patients to assess safety. Period
to strict stopping rules have been formalized:
Intervention
Cisplatin (Day 1: 75mg/m2) and Pemetrexed (Day 1: 500mg/m2 for non-squamous) or
Etoposide (Day1-3 100mg/m2 for squamous), 3-weekly regimens, together with
radiotherapy (24 daily fractions of 2.42 Gy to the mediastinal lymph nodes
with an integrated boost of 2.75 Gy to the primary tumour)
Study burden and risks
Concurrent chemoradiotherapy is a demanding treatment with a high rate of grade
3-4 side effects and a small risk of treatment-related death. The current
standard is either low-dose cisplatin regimen with hypofractionated
radiotherapy (24 fractions of 2.75 Gy in 24 days) for the NKI-AVL or a
cisplatin-doublet with a 6-weekly irradiation schedule (30 fractions of 2 Gy).
The standard dose 3-weekly chemotherapy regimens cause higher rates of systemic
side effects but will be limited by a total of two cycles. This is supported by
the RTOG 9410-trial , in which patients were treated with 2 cycles of
cisplatine and vinblastine and randomized to a sequential or concurrent
radiotherapy schedule. Patients treated with a concurrent schedule showed a
significant better 5-year overall survival. A second argument is that the
hypofractionated radiotherapy may cause an increase of the acute pulmonary and
esophageal toxicity. bBy limiting the number of courses to a total of two, we
expect that these side effects will be tolerable.
Plesmanlaan 121
AMSTERDAM 1066CX
NL
Plesmanlaan 121
AMSTERDAM 1066CX
NL
Listed location countries
Age
Inclusion criteria
1. Provision of signed, written and dated informed consent prior to any study specific procedures
2. Male or female aged 18 years or older
3. Cytological or histological proven NSCLC stage III or inoperable stage II (cT1*3*3N0-1), according to the 8th edition of the AJCC staging, with a clinical indication for concurrent chemo-irradiation.
4. Patients with locoregional recurrent lung tumor following surgery or a second primary cancer are eligible, unless a pneumonectomy was performed.
5. Minimum required laboratory data
a. Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) *1.5 x 109/L, platelets * 100 x 109/L, and hemoglobin * 5.5 mmol/L.
b. Hepatic:
i. Serum bilirubin * 1.5 times the upper limit of normal (× ULN); alkaline phosphatase (AP), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) * 3.0 × ULN.
ii. This does not apply to patients with confirmed Gilbert*s syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) who will be allowed in consultation with their physician.
c. Renal: GFR * 60 ml/min; if below this threshold a creatinine clearance (CrCL) can be calculated based on the original weight based Cockcroft and Gault formula and should be * 45 ml/min.
Exclusion criteria
1. WHO*performance status * 2
2. FEV1 and DLCO < 35 % of the age- and sex*adjusted normal value
3. Patients with grade 3 dyspnea or worse at baseline (according to CTCAE version 4.03)
4. Prior radiotherapy to the thorax.
5. Participation in another clinical study with an investigational product during the last 4 weeks.
6. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
7. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of chemotherapy.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
9. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow*up schedule; those conditions should be discussed with the patient before registration in the trial
10. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
11. Any condition that, in the opinion of the investigator, would interfere with evaluation of the chemoradiotherapy or interpretation of patient safety or study results
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 | EUCTR2016-003790-18-NL |
| ClinicalTrials.gov | NCT02947113 |
| CCMO | NL57625.031.16 |