Clinical trial NCT02025218: Iressa Re-challenge in Advanced NSCLC EGFR-mutated Patients
Official title: Iressa Re-challenge in Advanced NSCLC EGFR Mutated Patients Who Responded to an EGFR-TKI Used as First-line or Previous Treatment (NVALT 16)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: NSCLC
EGFR
TKI
Re-challenge
Lung Cancer
Resistance
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2013-12-31
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the effect of re-administration of gefitinib to EGFR-mutated NSCLC patients who had been treated with at least one line of TKIs followed by another line of treatment (non-TKI)

Detailed description: Rationale: Gefitinib is a registered first-line treatment for EGFR-mutated NSCLC patients. There is a lack of evidence for second and third line therapies in this category of patients. Several case reports have described successful re-administration of gefitinib to NSCLC patients who achieved objective response with the initial administration of gefitinib before eventual progression.

Objective: The primary objective of this study is to evaluate the disease control rate (DCR; confirmed complete response (CR) or partial response (PR), or stable disease (SD)) of gefitinib using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 in patients with activating sensitising Epidermal Growth Factor mutation positive (EGFR M+) NSCLC. The secondary objectives of the study are: objective response rate (ORR) according to RECIST, progression free survival (PFS) according to RECIST, overall Survival (OS), EGFR Mutational status of tumour tissue both activating and resistance EGFR mutations analysis and the association between the Veristrat assay (Biodesix) and both PFS and OS will be assessed.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed NSCLC with an activating sensitising EGFR TK mutation as determined before starting the first EGFR-TKI treatment by using a well-validated and robust methodology
* Female or male patients aged 18 years or over with locally advanced or metastatic stage IIIB/IV disease, not suitable for therapy of curative intent or stage IV (metastatic) disease, eligible for gefitinib re-challenge treatment for NSCLC who have already received an EGFR-TKI with a documented complete (CR) or partial response (PR) or stable disease (SD) \>12 weeks as the best response to their 1st EGFR-TKI treatment and who have received any subsequent anti-cancer therapy (excluding EGFR-TKIs) treatment, including but not limited to doublet platinum based chemotherapy or docetaxel monotherapy or pemetrexed monotherapy, on which they progressed.
* Measurable disease defined as at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with spiral CT or MRI and which is suitable for accurate repeated measurements.
* WHO / ECOG / Zubrod performance status 0-2.
* Possibility of obtaining tumour material before the start of the study treatment.

Exclusion Criteria:

* Known severe hypersensitivity to gefitinib or any of the excipients of the product treatment with no persistent radiation toxicity. Previous adjuvant chemotherapy is allowed.
* Progressive disease or stable disease (SD) \<12 weeks as best response to the 1st line treatment with an EGFR-TKI
* Consideration to require radiotherapy to the lung at the time of study entry or in the near future
* Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease. Pre-existing idiopathic pulmonary fibrosis evidenced by CT scan at baseline
* Known or suspected brain metastases or spinal cord compression, unless treated with surgery and/or radiation.
* Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy
* Concomitant use of known CYP 3A4 inducers such as phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort
* Pregnancy or breast-feeding
* As judged by the investigator, any evidence of severe or uncontrolled systemic disease (eg, unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
* Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
* Other co-existing malignancies or malignancies diagnosed within the last 2 years with the exception of basal cell carcinoma or cervical cancer in situ
* Life expectancy of less than 12 weeks
* Treatment with a non-approved or investigational drug within 30 days before day 1 of study treatment
* Involvement in the planning and/or conduct of the study (applies to both NVALT staff or staff at the study site)
* Previous enrolment or treatment in the present study.

Primary outcomes:
measure: Disease control rate
timeFrame: 6 months after last included patient
Secondary outcomes:
Other outcomes:
Locations:
city: Almelo
country: Netherlands
facility: Ziekenhuis Groep Twente
city: Amsterdam
country: Netherlands
facility: VU University medical Center
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuis
city: Assen
country: Netherlands
facility: Wilhelmina Ziekenhuis Assen
city: Beverwijk
country: Netherlands
facility: Rode Kruis ziekenhuis
city: Deventer
country: Netherlands
facility: Deventer ziekenhuis
city: Ede
country: Netherlands
facility: Gelderse vallei
city: Eindhoven
country: Netherlands
facility: Catharina ziekenhuis
city: Groningen
country: Netherlands
facility: Martini ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina ziekenhuis
city: Rotterdam
country: Netherlands
facility: Maasstad ziekenhuis
city: Venlo
country: Netherlands
facility: VieCurie Hospital
city: Zwolle
country: Netherlands
facility: Isala klinieken
Study officials:
References: