Docetaxel Versus Intercalated Erlotinib-docetaxel in Patients With Relapsed EGFR Wild Type, ALK Negative Non Squamous Cell Carcinoma

Carcinoma, Non-small Cell Lung Clinical Trial

Official title:

A Randomized Phase III Study of Docetaxel Versus Intercalated Erlotinib Docetaxel Combination Therapy in Patients With Relapsed EGFR (Epidermal Growth Factor Receptor) Wild Type, ALK(Anaplastic Lymphoma Kinase) Negative Non Squamous Cell Carcinoma. (NVALT 18 Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02775006
• Other study ID #: NVALT 18
• Status: Terminated
• Phase: Phase 3
• Start date: October 14, 2016
• Est. completion date: April 2019

Study information

• Verified date: April 2019
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The aim 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.

As pemetrexed is standard first line treatment, the combination of erlotinib docetaxel in non-squamous NSCLC should be investigated as second line treatment. Also the question has to be answered whether the combination outperforms monotherapy treatments.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: April 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Immunotherapy pretreatment is allowed

2. Complete recovery from prior chemotherapy side effects to < Grade 2.

3. At least one unidimensionally measurable lesion meeting RECIST criteria.

4. ECOG PS 0-1.

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 (upper limit normal), AP, ALT, AST = 1.5 x ULN. AP, ALT, and AST =5 x ULN is acceptable if the liver has tumor involvement.

• Renal: calculated creatinine clearance = 40 ml/min based on the Cockcroft-Gault formula.

7. 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.

8. Signed informed consent.

9. Patient compliance and geographical proximity that allow adequate follow up.

10. Patients who have undergone cranial irradiation for brain metastases more than 4 weeks before inclusion in our protocol, provided that they are clinically fit to undergo second line treatment

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 at least 4 weeks before enrollment and has been off corticosteroids for at least two weeks before enrollment. Prophylactic irradiation at least 4 weeks prior to enrollment is accepted.

4. Maintenance treatment with erlotinib or other TKI (Tyrosine Kinase Inhibitor), or docetaxel. Maintenance treatment with pemetrexed is allowed. Previous treatment with an EGFR-TKI or docetaxel within 6 months prior to enrollment.

5. Inability or unwillingness to take dexamethasone.

6. Concomitant treatment with any other experimental drug under investigation.

7. Patients experiencing disease progression within 2 months after the start of platinum based chemotherapy

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-small Cell Lung
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Docetaxel
75mg/m2
• Erlotinib
150mg/day

Locations

Country	Name	City	State
Netherlands	VUmc Medical Center	Amsterdam	Noord-Holland
Netherlands	Gelre Ziekenhuis	Apeldoorn
Netherlands	Amphia Hospital	Breda
Netherlands	Jeroen Bosch Hospital	Den Bosch
Netherlands	Haga	Den Haag
Netherlands	Albert Schweitzer ziekenhuis	Dordrecht
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	MCL	Leeuwarden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Laurentius Hospital	Roermond
Netherlands	Erasmus MC	Rotterdam
Netherlands	Ikazia	Rotterdam
Netherlands	St. Fransicus Gasthuis	Rotterdam
Netherlands	Medical Center Haaglanden	the Hague
Netherlands	St. Antonius ziekenhuis	Utrecht
Netherlands	VieCuri Medisch Centrum voor Noord-Limburg	Venlo

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Dutch Society of Physicians for Pulmonology and Tuberculosis

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Erlotinib dose level variance in blood	Therefore in patients on erlotinib every 6 weeks through dose levels in blood will be determined	Every six weeks from randomisation up until last treatment administration (up until 48 weeks)
Primary	progression free survival		from the date of randomization to the first date of progression of disease or of death from any cause up to 24 months after last treatment administration
Secondary	quantitative and qualitative adverse events	Adverse events will be graded according to NCI Common Toxicity Criteria version 4.03	from the date of randomization until resolution or stabilization of the event and up to 30 days after the last study medication/treatment
Secondary	response rates		Every six weeks from date of randomization until the date of first documented progression or date of death from any cause up to 24 months after last treatment administration
Secondary	duration of response		from the date of the first objective status assessment of a complete or partial response to the first date of progression of disease or death from any cause up to 24 months after last treatment administration
Secondary	overall survival	Evaluation of overall survival (OS)	from the date of randomization to the date of death from any cause up to 24 months after last treatment administration