The objective of this study is to investigate the effect of docetaxel monotherapy and the combination of docetaxel intercalated erlotinib in patients with relapsed EGFR wild type, ALK negative non squamous cell carcinoma.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare progression free survival between docetaxel and erlotinib-docetaxel
in patients with relapsed EGFR wild type, ALK negative non squamous cell
carcinoma patients.
Secondary outcome
To characterize the quantitative and qualitative toxicities of these regimens,
response rates and duration of response for responding patients, and survival.
In addition, pharmacokinetic parameters will be studied for both drugs, thereby
studying the influence these drugs on each others exposure and the influence of
genetic and environmental factors in individual patients.
Background summary
Based on phase III trials, showing either superior survival as compared to best
supportive care only or equal therapeutic efficacy, several agents are now
approved for use as second line treatment in advanced NSCLC. These include
docetaxel, pemetrexed and erlotinib. The Nederlandse Vereniging van Artsen voor
Longziekten en Tuberculose (Dutch Association of Pulmonologists, NVALT) has
completed a randomized phase II study comparing pemetrexed with a combination
of carboplatin and pemetrexed. The results of this study showed that
progression free survival is superior in patients treated with the doublet
combination. Sample size precluded a survival analyses but results of the NVALT
study were combined with those of an identical Italian study. This analysis
showed that the benefit of the combination was restricted to the squamous cell
population patients. In this histological subtype it is known that pemetrexed
has lower efficacy.
One way to improve on these results is to investigate novel erlotinib (an
EGFR-TKI) based combinations. A recent study by NVALT investigated the efficacy
of erlotinib monotherapy versus chemotherapy and intercalated erlotinib in
relapsed patients with NSCLC. The chemotherapeutic agent was dependent on
histology, docetaxel for squamous and pemetrexed for non squamous histology.
As combinations of concurrent platinum based doublet chemotherapy and erlotinib
have failed to show a survival advantage in untreated NSCLC patients based on
preclinical research sequentially administered cytotoxic therapy and EGFR TKI*s
was chosen. The study revealed that there was no difference in PFS and OS for
the total population of patients. But preplanned subgroup analysis revealed
that both PFS and OS were significantly prolonged in the non-squamous NSCLC.
As pemetrexed is now mostly used as first line treatment the combination of
erlotinib docetaxel in non-squamous NSCLC should be investigated in further
research. Also the question has to be answered whether the combination
outperforms the monotherapy treatment.
Study objective
The objective of this study is to investigate the effect of docetaxel
monotherapy and the combination of docetaxel intercalated erlotinib in
patients with relapsed EGFR wild type, ALK negative non squamous cell
carcinoma.
Study design
After stratification for ECOG-performance status (0-1), response to prior
treatment (CR, PR, SD versus PD), treatment free interval after platinum based
therapy (<6 months versus >6 months) and maintenance, patients will be
centrally randomized to receive either docetaxel (arm A) or docetaxel plus
erlotinib (arm B).
Intervention
Arm A: docetaxel 75mg/m2 every 21 days until disease progression or toxicity
related.
Arm B: docetaxel 75mg/m2 on day 1 plus erlotinib 150mg/day days 2-16, every 21
days, until disease progression, or toxicity related. In case of toxicity due
to docetaxel continuation with erlotinib is allowed.
Study burden and risks
The risks in participation are the same risks patients would undergo receiving
the same standard treatment. All extra blood samples will be taken during
regular blood draws, except for the PK group in Erasmus MC; they will have
samples taken outside the regular draws.
Patients in the PK group (Erasmus MC only) may experience bruising due to extra
blood draws.
Luijbenstraat 15
's-Hertogenbosch 5211BR
NL
Luijbenstraat 15
's-Hertogenbosch 5211BR
NL
Listed location countries
Age
Inclusion criteria
1. Histologically or cytologically confirmed EGFR wild type, ALK negative, non squamous cell carcinoma, locally advanced and metastatic disease stage IIIB and IV. Evidence of disease progression after one cytotoxic treatment platinum containing regimen or immunotherapy.
2. ECOG PS 0-1.
3. Age > 18 years.
Exclusion criteria
1. Patients with medical risks because of non-malignant disease as well as those with active uncontrolled infection.
2. Concomitant treatment with any other experimental drug under investigation.
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 | EUCTR2015-000129-34-NL |
| ClinicalTrials.gov | NCT02775006 |
| CCMO | NL44814.031.15 |