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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— NVALT10  

Official title:

A Randomized Phase II Study of Erlotinib Compared to Single Agent Chemotherapy-erlotinib Combination in Pretreated Patients With Advanced NSCLC (NVALT10 Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00835471
• Other study ID #: NVALT10
• Status: Completed
• Phase: Phase 2
• Start date: March 2009
• Est. completion date: June 2019

Study information

• Verified date: September 2020
• Source: Dutch Society of Physicians for Pulmonology and Tuberculosis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: June 2019
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

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.
• erlotinib
erlotinib 150 mg/day continuously until disease progression

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
Dutch Society of Physicians for Pulmonology and Tuberculosis

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

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 — View 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 c — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	to compare the PFS in the group receiving erlotinib alone versus the patients receiving erlotinib + single agent Progression free survival	From randomisation to date of first progression or date of death, assessed up to 36 months
Secondary	Number of Adverse Events	to compare relevant toxicity (CTC AE vs 3.0) in the group receiving erlotinib alone versus the patients receiving erlotinib + single agent	From randomisation to 30 days after EoT all AEs are collected

External Links

•   Dutch Society of Physicians for Pulmonology and Tuberculosis (NVALT)