This randomized, open label phase III trial will be performed in patients with squamous carcinoma of the lung. The objectives of the trial are to compare the efficacy of afatinib with erlotinib as maintenance and second-line treatment for this group…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free Survial (PFS)
Secondary outcome
- Overall Survival (OS)
- Objective response
- Disease control
- Tumour shrinkage
- Health related quality of life (QoL)
- Safety
Background summary
Treatment options for patients with advanced squamous cell carcinoma of the
lung are limited following first line chemotherapy with most patients recurring
and eventually succumbing to their disease. For patients eligible to tolerate,
chemotherapy has been an option and docetaxel is indicated in the second line
setting for patients with advanced NSCLC with associated chemotherapy related
morbidity. The EGFR pathway has been shown to play a significant role in
propagation of human epithelial malignancies including NSCLC. Erlotinib
inhibits the TK domain of the EGFR and is indicated in the treatment of NSCLC
following failure of one prior chemotherapy regimen or in patients not
progressing after receiving four cycles of platinum based chemotherapy.
Patients with adenocarcinoma tend to derive higher response rates than other
histologies of NSCLC in erlotinib trials. There remains thus a significant void
for patients with squamous cell carcinoma of the lung whose therapeutic options
are limited in the second line and maintenance setting.
Afatinib is an irreversible EGFR inhibitor with a favourable risk benefit ratio
that is currently in Phase 3 clinical trials in lung cancer, breast cancer and
squamous cancer of head and neck (SCCHN). The clinical experience of afatnib
includes over 2000 patients. Afatinib is relatively well tolerated, with most
common adverse events being diarrhhea, rash and stomatitis as expected for this
class of agents.
Afatinib has shown evidence of clinical activity in patients with Squamous
cancer of the head and neck in a randomized clinical Phase 2 trial and early
evidence of clinical activity in patients with squamous carcinoma of the lung
in ongoing clinical trials.
Study objective
This randomized, open label phase III trial will be performed in patients with
squamous carcinoma of the lung. The objectives of the trial are to compare the
efficacy of afatinib with erlotinib as maintenance and second-line treatment
for this group of patients.
Study design
A randomized phase III open-label trial
Intervention
Patients will be randomized to receive a 2nd line cancer treatment of either
afatinib or erlotinib.
Study burden and risks
Patients will be screened for elegibility for the trial (Full physical exam,
Limited physical exam, ECOG Performance Score, ECG, echo or MUGA scans, blood
samples and CT/MRI voor tumor assessment. Treatment follows with an oral
tablet intake for 28 days per cycle.
During the first treatment cycle the patients will visit the clinic twice (day
1 and day 8), thereafter only once every 28 days.
CT scans (or MRI) will be performed at week 8, 12, 16 , and every 8 weeks
thereafter.
Comeniusstraat 6
ALKMAAR 1817 MS
NL
Comeniusstraat 6
ALKMAAR 1817 MS
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of advanced stage NSCLC squamous histology , including mixed histology.;2. Completion of at least 4 cycles of platinum-based doublet chemotherapy, with or without additional [non-EGFR] targeted agents, as 1st line treatment of Stage IIIB/IV NSCLC. Note the below scenarios are also considered to meet this requirement:;A) Patients relapsing within 6 months of receiving adjuvant-intent/neo-advjuvant/curative-intent chemoradiotherapy/chemoradiotherapy(Note: these patients are still to have had the equivalent of 4 cycles of platinum-based doublet chemotherapy exept in setting below).;OR;B) Patients intending to recieve four cycles of platinum-based doublet chemotherapy but due to toxicity, and not PD, discontinue just the platinum agent after at least two cycles of platinum doublet had been administered.;3. Eligible to receive 2nd line therapy in the opinion of the investigator.;4. Measurable disease according to RECIST 1.1 (R09-0262). ;5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 (R01-0787). ;6. Availability of tumour tissue material for correlative studies. Archived tumour tissue is acceptable.;7. Adequate organ function.
Exclusion criteria
1. Prior treatment with EGFR directed small molecules or antibodies.;2. Curative intent chemoradiotherapy as the only treatment for stage IIIB NSCLC unless relapse occurs within 6 months of completion of treatment, and in the opinion of the investigator the patient has received an equivalent of 4 cycles of platinum-based doublet therapy.;3. Radiotherapy within 4 weeks prior to randomization.;4. Active brain metastases (stable for <4 weeks, symptomatic, or leptomeningeal disease). Dexamethasone therapy will be allowed if administered as a stable dose for at least 4 weeks before randomization.;5. Patients without Progressive Disease
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 | EUCTR2011-002380-24-NL |
| ClinicalTrials.gov | NCT01523587 |
| CCMO | NL37158.060.11 |