2nd Line Erlotinib Treatment With (Out) Chemotherapy of Advanced Non Small Cell Lung Cancer (NSCLC) (NVALT10)

• ClinicalTrials.gov Identifier: NCT00835471
• Recruitment Status: Completed
• First Posted: February 3, 2009
• Last Update Posted: September 29, 2020
• Sponsor: Dutch Society of Physicians for Pulmonology and Tuberculosis
• Information provided by (Responsible Party): Dutch Society of Physicians for Pulmonology and Tuberculosis

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: erlotinib plus docetaxel or pemetrexed; Drug: erlotinib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 195 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2009
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: June 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Erlotinib plus docetaxel (squamous cell NSCLC) or pemetrexed (non-squamous cell NSCLC)	Drug: erlotinib plus docetaxel or pemetrexed; non-squamous carcinoma: pemetrexed 500 mg/m2 on Day 1 plus erlotinib 150 mg/day days 2-16, every 21 days. Pemetrexed will be given for a maximum of 4 cycles. Thereafter erlotinib will be continued continuously until disease progression. squamous carcinoma: Docetaxel 75mg/m2 on Day 1 plus erlotinib 150mg/day days 2-16, every 21 days. Docetaxel will be given for a maximum of 4 cycles. Thereafter erlotinib will be continued continuously until disease progression.; Other Names: Tarceva; Taxotere; Alimta
Active Comparator: 2; Erlotinib	Drug: erlotinib; erlotinib 150 mg/day continuously until disease progression; Other Name: Tarceva

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: From randomisation to date of first progression or date of death, assessed up to 36 months ]
   to compare the PFS in the group receiving erlotinib alone versus the patients receiving erlotinib + single agent Progression free survival

Secondary Outcome Measures :

1. Number of Adverse Events [ Time Frame: From randomisation to 30 days after EoT all AEs are collected ]
   to compare relevant toxicity (CTC AE vs 3.0) in the group receiving erlotinib alone versus the patients receiving erlotinib + single agent

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Netherlands

VU medisch centrum

Amsterdam, Netherlands

Rode Kruis Ziekenhuis

Beverwijk, Netherlands

Amphia Ziekenhuis

Breda, Netherlands

Reinier de Graaf Gasthuis

Delft, Netherlands

Jeroen Bosch Ziekenhuis

Den Bosch, Netherlands

Catharina-Ziekenhuis

Eindhoven, Netherlands

Martini Ziekenhuis

Groningen, Netherlands

Kennemer Gasthuis

Haarlem, Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

Universitair Medisch Centrum Sint Radboud

Nijmegen, Netherlands

Maasstad Ziekenhuis

Rotterdam, Netherlands

Sint Franciscus Gasthuis

Rotterdam, Netherlands

HagaZiekenhuis

The Hague, Netherlands

Isala Klinieken

Zwolle, Netherlands

Sponsors and Collaborators

Dutch Society of Physicians for Pulmonology and Tuberculosis

Investigators

• Study Director: Joachim G. Aerts, MD PhD; Amphia Ziekenhuis, Breda, The Netherlands
• Study Director: Henk E. Coderington, MD; HagaZiekenhuis, The Hague, The Netherlands

More Information

Additional Information:

Dutch Society of Physicians for Pulmonology and Tuberculosis (NVALT) 

Publications of Results:

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Dutch Society of Physicians for Pulmonology and Tuberculosis
• ClinicalTrials.gov Identifier: NCT00835471
• Other Study ID Numbers: NVALT10
• First Posted: February 3, 2009
• Last Update Posted: September 29, 2020
• Last Verified: September 2020

Keywords provided by Dutch Society of Physicians for Pulmonology and Tuberculosis:

Lung cancer; non-small-cell; erlotinib; chemotherapy

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Docetaxel; Pemetrexed; Erlotinib Hydrochloride; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors