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

Phase 3
Terminated
Conditions
Carcinoma, Non-small Cell Lung
Interventions
Registration Number
NCT02775006
Lead Sponsor
The Netherlands Cancer Institute
Brief 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.

Detailed 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 & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
45
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DocetaxelDocetaxelDocetaxel 75mg/m2 every 21 days until disease progression or toxicity related
Docetaxel plus erlotinibDocetaxelDocetaxel 75mg/m2 on Day 1 plus erlotinib 150mg/day days 2-16, every 21 days, until disease progression, or toxicity related.
Docetaxel plus erlotinibErlotinibDocetaxel 75mg/m2 on Day 1 plus erlotinib 150mg/day days 2-16, every 21 days, until disease progression, or toxicity related.
Primary Outcome Measures
NameTimeMethod
progression free survivalfrom 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 Outcome Measures
NameTimeMethod
quantitative and qualitative adverse eventsfrom the date of randomization until resolution or stabilization of the event and up to 30 days after the last study medication/treatment

Adverse events will be graded according to NCI Common Toxicity Criteria version 4.03

overall survivalfrom the date of randomization to the date of death from any cause up to 24 months after last treatment administration

Evaluation of overall survival (OS)

response ratesEvery 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
duration of responsefrom 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

Trial Locations

Locations (19)

VUmc Medical Center

🇳🇱

Amsterdam, Noord-Holland, Netherlands

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Laurentius Hospital

🇳🇱

Roermond, Netherlands

Gelre Ziekenhuis

🇳🇱

Apeldoorn, Netherlands

Haga

🇳🇱

Den Haag, Netherlands

Maastricht University Medical Center

🇳🇱

Maastricht, Netherlands

VieCuri Medisch Centrum voor Noord-Limburg

🇳🇱

Venlo, Netherlands

Medical Center Haaglanden

🇳🇱

the Hague, Netherlands

St. Antonius ziekenhuis

🇳🇱

Utrecht, Netherlands

Amphia Hospital

🇳🇱

Breda, Netherlands

Albert Schweitzer ziekenhuis

🇳🇱

Dordrecht, Netherlands

Martini Ziekenhuis

🇳🇱

Groningen, Netherlands

Jeroen Bosch Hospital

🇳🇱

Den Bosch, Netherlands

Ziekenhuis Gelderse Vallei

🇳🇱

Ede, Netherlands

Spaarne Gasthuis

🇳🇱

Hoofddorp, Netherlands

Maxima Medisch Centrum

🇳🇱

Eindhoven, Netherlands

MCL

🇳🇱

Leeuwarden, Netherlands

St. Fransicus Gasthuis

🇳🇱

Rotterdam, Netherlands

Ikazia

🇳🇱

Rotterdam, Netherlands

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