Clinical trial NCT00835471: 2nd Line Erlotinib Treatment With (Out) Chemotherapy of Advanced Non Small Cell Lung Cancer (NSCLC)
Official title: A Randomized Phase II Study of Erlotinib Compared to Single Agent Chemotherapy-erlotinib Combination in Pretreated Patients With Advanced NSCLC (NVALT10 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Lung cancer
non-small-cell
erlotinib
chemotherapy
Lead sponsor: Dutch Society of Physicians for Pulmonology and Tuberculosis
Sponsor class: OTHER
First posted: 2009-02-03
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess if the combination of erlotinib and chemotherapy (docetaxel in case of squamous cell NSCLC or pemetrexed in case of other histological types) is superior to erlotinib alone and has acceptable tolerability and safety in the 2nd line treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC).

Detailed description: Open randomized multicenter phase II study in patients in need of 2nd line treatment for advanced/metastatic NSCLC. Efficacy and safety of monotherapy with erlotinib will be compared with combination therapy of erlotinib and chemotherapy. In recent studies it was established that pemetrexed activity is more pronounced in non-squamous NSCLC in comparison to squamous cell carcinoma. Therefore in patients with non-squamous carcinoma pemetrexed will be used. As in second line treatment of NSCLC docetaxel is registered also for usage in patients with squamous cell carcinoma, docetaxel will be used in patients with squamous histology.

Chemotherapy will be limited to 4 courses. Erlotinib will be continued until disease progression or unacceptable toxicity.

Erlotinib as monotherapy will be administered continuously. In combination with chemotherapy, erlotinib will be given from day 2-16 of every course of 3 weeks.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed NSCLC, locally advanced and metastatic disease stage IIIB and IV. Evidence of disease progression after one or two cytotoxic treatment regimens which should have included a platinum agent.
2. Complete recovery from prior chemotherapy side effects to \< Grade 2.
3. At least one unidimensional measurable lesion meeting RECIST criteria.
4. ECOG PS 0-2.
5. Age \> 18 years.
6. Adequate organ function, 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 \< 1.5 x ULN AP, ALT, and AST \<5 x ULN is acceptable if the liver has tumor involvement
   * Renal: calculated creatinin clearance \> 40 ml/min based on the Cockcroft-Gault formula.
7. Estimated life expectancy \>12 weeks.
8. Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate. Female patients with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
9. Signed informed consent.
10. Patient compliance and geographical proximity that allow adequate follow up.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with medical risks because of non-malignant disease as well as those with active uncontrolled infection.
3. Documented brain metastases unless the patient has completed local therapy for central nervous system metastases and has been off corticosteroids for at least two weeks before enrollment.
4. Previous treatment with an EGFR-TKI, or in non-squamous histology earlier treatment with pemetrexed and in squamous earlier treatment with docetaxel.
5. Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (5 day period for long-acting agents such as piroxicam).
6. Inability or unwillingness to take folic acid, vitamin B-12 supplementation or dexamethasone.
7. Concomitant treatment with any other experimental drug under investigation.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomisation to date of first progression or date of death, assessed up to 36 months
Secondary outcomes:
measure: Number of Adverse Events
timeFrame: From randomisation to 30 days after EoT all AEs are collected
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU medisch centrum
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina-Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum Sint Radboud
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
city: The Hague
country: Netherlands
facility: HagaZiekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Amphia Ziekenhuis, Breda, The Netherlands
name: Joachim G. Aerts, MD PhD
role: STUDY_DIRECTOR
affiliation: HagaZiekenhuis, The Hague, The Netherlands
name: Henk E. Coderington, MD
role: STUDY_DIRECTOR
References:
citation: De Ruysscher D, Dingemans AC, Praag J, Belderbos J, Tissing-Tan C, Herder J, Haitjema T, Ubbels F, Lagerwaard F, El Sharouni SY, Stigt JA, Smit E, van Tinteren H, van der Noort V, Groen HJM. Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non-Small-Cell Lung Cancer: A Randomized Phase III NVALT-11/DLCRG-02 Study. J Clin Oncol. 2018 Aug 10;36(23):2366-2377. doi: 10.1200/JCO.2017.77.5817. Epub 2018 May 22.
citation: Witlox WJA, Ramaekers BLT, Groen HJM, Dingemans AM, Praag J, Belderbos J, van der Noort V, van Tinteren H, Joore MA, De Ruysscher DKM. Factors determining the effect of prophylactic cranial irradiation (PCI) in patients with stage-III nonsmall cell lung cancer: exploratory subgroup analyses of the NVALT-11/DLCRG-02 phase-III study. Acta Oncol. 2019 Oct;58(10):1528-1531. doi: 10.1080/0284186X.2019.1629016. Epub 2019 Jul 1. No abstract available.
citation: Witlox WJA, Ramaekers BLT, Joore MA, Dingemans AC, Praag J, Belderbos J, Tissing-Tan C, Herder G, Haitjema T, Ubbels JF, Lagerwaard J, El Sharouni SY, Stigt JA, Smit EF, van Tinteren H, van der Noort V, Groen HJM, De Ruysscher DKM. Health-related quality of life after prophylactic cranial irradiation for stage III non-small cell lung cancer patients: Results from the NVALT-11/DLCRG-02 phase III study. Radiother Oncol. 2020 Mar;144:65-71. doi: 10.1016/j.radonc.2019.10.016. Epub 2019 Nov 14.
citation: Aerts JG, Codrington H, Lankheet NA, Burgers S, Biesma B, Dingemans AM, Vincent AD, Dalesio O, Groen HJ, Smit EF; NVALT Study Group. A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: the NVALT-10 study. Ann Oncol. 2013 Nov;24(11):2860-5. doi: 10.1093/annonc/mdt341. Epub 2013 Aug 28.