Clinical trial NCT02775006: Docetaxel Versus Intercalated Erlotinib-docetaxel in Patients With Relapsed EGFR Wild Type, ALK Negative Non Squamous Cell Carcinoma
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Carcinoma, Non-small Cell Lung
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Dutch Society of Physicians for Pulmonology and Tuberculosis
First posted: 2016-05-17
Enrollment: 45
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 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).

Eligibility criteria: 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

Primary outcomes:
measure: progression free survival
timeFrame: 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 outcomes:
measure: quantitative and qualitative adverse events
timeFrame: from the date of randomization until resolution or stabilization of the event and up to 30 days after the last study medication/treatment
measure: response rates
timeFrame: 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
measure: duration of response
timeFrame: 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
measure: overall survival
timeFrame: from the date of randomization to the date of death from any cause up to 24 months after last treatment administration
Other outcomes:
measure: Erlotinib dose level variance in blood
timeFrame: Every six weeks from randomisation up until last treatment administration (up until 48 weeks)
Locations:
city: Amsterdam
country: Netherlands
facility: VUmc Medical Center
state: Noord-Holland
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Den Haag
country: Netherlands
facility: Haga
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Leeuwarden
country: Netherlands
facility: MCL
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Roermond
country: Netherlands
facility: Laurentius Hospital
city: Rotterdam
country: Netherlands
facility: St. Fransicus Gasthuis
city: Rotterdam
country: Netherlands
facility: Ikazia
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: the Hague
country: Netherlands
facility: Medical Center Haaglanden
city: Utrecht
country: Netherlands
facility: St. Antonius ziekenhuis
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum voor Noord-Limburg
Study officials:
affiliation: Dutch Society of Physicians for Pulmonology and Tuberculosis
name: Joachim G Aerts, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: