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Non-squamous Non-small Cell Lung Cancer Stage IIPhase 2/3NeoIntercalNCT02326285

Induction Therapy With Intercalated Tyrosine Kinase Inhibitor (TKI) and Chemotherapy in NSCLC With Activating Epidermal Growth Factor Receptor (EGFR) Mutation in Stages II-IIIB

A Phase 2/3 study testing Gefitinib, docetaxel and cisplatin in people with Non-squamous Non-small Cell Lung Cancer Stage II and Non-squamous Non-small Cell Lung Cancer Stage IIIA, run by AIO-Studien-gGmbH at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is designed as a single arm, un-controlled, open-label, multi-center hypothesis generating two-stage phase II trial. It is based on the assumption that the proposed treatment scheme doubles the rate of pathologic complete remission in Mutated epidermal growth factor receptor (EGFRmt) + NSCLC patients… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gefitinib, docetaxel and cisplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteGermany
Study dates
Nov 2015to Jan 2018
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically or cytologically confirmed non-squamous non-small-cell lung cancer (NSCLC) stage II, IIIA and IIIB detected preoperatively by adequate methods and activating EGFR mutation in exons 18-21 and deemed to be able to undergo curative surgery after induction therapy. Stage should be confirmed by PET-CT as well as adequate mediastinal staging. MRI of the brain to exclude CNS metastases is mandatory.
  • At least one unidimensionally measurable lesion meeting RECIST criteria (version 1.1);
  • Performance status of 0 to 1 on the ECOG scale;
  • Estimated life expectancy of at least 12 weeks;
  • Patients aged ≥ 18 years;
  • Adequate organ function including the following:
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  • Adequate bone marrow reserve:
  • absolute neutrophils (segmented and bands) count (ANC) ≥1.5x109/L;
  • platelets ≥100x109/L;
  • haemoglobin ≥9 g/dL.
  • Hepatic:
  • bilirubin ≤ 1xULN;
  • alkaline phosphatase (AP);
  • aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5xULN.
  • Renal:
  • serum creatinine ≤ 1.3 mg/dL
  • glomerular filtration rate (GFR) ≥ 70 mL/min for cisplatinum based CTx;
  • If contraindications including GFR below 70mL/minagainst cisplatin exist, carboplatin may also be used;
  • glomerular filtration rate ≥ 30 mL/min (calculated) if carboplatin is to be used
  • Adequate lung function tests as assessed by body plethysmography, diffusion test and if necessary spiro-ergometry.
  • Cooperation and willingness to complete all aspects of the study;
  • Written informed consent to participate in the study.

Who cannot join

  • EGFR wild type configuration;
  • EGFR resistance mutations (i.e. T790M);
  • Significant cardiovascular disease, such as uncontrolled hypertension, myocardial infarction within the last 6 months, unstable angina pectoris, CHF ≥ NYHA 2, serious arrhythmia, significant peripheral vascular disease;
  • Pre-existing neuropathic ≥ grade 2;
  • Patients with confirmed HIV infection. HIV testing is not mandatory.
  • Prior history of malignancy except for basal cell carcinoma or carcinoma in situ of the cervix, and with the exception of other malignancies after curative treatment with an interval of at least 3 years.
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  • Lactating or pregnant woman, woman of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are implants, injectable contraceptives, combined oral contraceptives, intrauterine devices (only hormonal devices), sexual abstinence or vasectomy of the partner). Woman of childbearing potential must have a negative pregnancy test (serum β-HCG) at visit 1.
  • Any other chemotherapy at start;
  • Treatment with other experimental drugs during the course of the study or within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
  • Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial;
  • Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
  • Patient has already been included in this trial;
  • Patients who do not understand the nature, the scope and the consequences of the clinical trial;
  • Affected persons who might be dependent on the sponsor or the investigator.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Pius-Hospital

    Oldenburg, 26121

Other trials in Germany

About this study

Official title: Induction Therapy With Gefitinib Followed by Taxane Platinum Chemotherapy and Intercalated Gefitinib in NSCLC Stages II-IIIB With Activating EGFR Mutation - A Single Arm Phase II Trial.

This study is designed as a single arm, un-controlled, open-label, multi-center hypothesis generating two-stage phase II trial. It is based on the assumption that the proposed treatment scheme doubles the rate of pathologic complete remission in Mutated epidermal growth factor receptor (EGFRmt) + NSCLC patients compared to historical control data from standard treatments.

Patients with NSCLC and activating EGFR mutation in stages II, IIIA and IIIB eligible for induction therapy with docetaxel and cisplatin and gefitinib

Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.

Read the detailed description

Based on the notion that neoadjuvant combination of Chemotherapy (CTx) and intercalated TKI is clinically beneficial, which can be inferred from prior study data and single case reports, this study aims to generate additional information on feasibility, safety and efficacy of this treatment approach in a larger group of EGFR mutated NSCLC patients. This study is a hypothesis generating two-stage trial for future phase III studies of neoadjuvant CTx with intercalated TKI. Hence, the study design relies entirely on a single treatment arm. To demonstrate efficacy it is sufficient to compare to historical data of the conventional treatments of NSCLC.

Being tested
Gefitinib, docetaxel, cisplatin, Surgery
Keywords
induction therapy, NSCLC, Non-small Cell Lung Cancer, curative surgery
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GefitinibDrug

    Also called IRESSA ®

    Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.

  • docetaxelDrug

    chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3).

  • cisplatinDrug

    chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3).

  • SurgeryProcedure or surgery

    Surgery should be performed in the 4th or at the latest 5th week after d1 of the last cycle of chemotherapy (d64 to 78).

Study groups in NCT02326285
Study groupRoleWhat they receive
Treatment phaseExperimentalEnrolled patients will be treated with 250mg/day Gefitinib for 11 days (day -12 until day -1) followed by 3 cycles (length 21 days) of chemotherapy with docetaxel (75mg/m2 d1) and cisplatin (50 mg/m2 d1+2) combined with intercalated gefitinib (250mg/day, d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.
Receives: Drug: Gefitinib; Drug: docetaxel; Drug: cisplatin; Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. pathologic complete remission rate (pCR rate)

    The primary objective of the study is to assess the pathologic complete remission rate after induction therapy with gefitinib d -12 to d-1 followed by docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 q21 and intercalated gefitinib 250 mg d4 to d20 (cycle 1 and 2) and d4-17 (for cycle3), in order to demonstrate feasibility and efficacy of this treatment scheme. It is expected to achieve a pCR ≥30% regression grade IIB and III (Junker criteria) compared to historical controls in the mediastinal lymph nodes.

    Measured: 12 weeks (after 3 cycles and surgery) after enrollment

Secondary outcomes (9)

  1. Adverse Events (AEs) / Serious adverse events (SAEs)

    AEs/SAEs from 21 patients during induction CTx with docetaxel and cisplatin in combination with intercalated gefitinib

    Measured: 30 months

  2. Surgical R0 resection rate

    R0 resection rate as assessed according to the German S3 guidelines

    Measured: 30 month

  3. Response: radiologic response based on CT

    Measured: 30 month

  4. progression free survival (PFS)

    Progression-free survival (PFS) will be defined as the time from enrollment to the time of disease progression or relapse or death, or to the date of last assessment without any such event (censored observation).

    Measured: 30 month

  5. Overall survival (OS)

    The duration of overall survival (OS) will be determined by measuring the time interval from enrollment to the date of death or last observation (censored).

    Measured: 30 month

  6. relapse pattern

    After the end of treatment will be performed every 3 month (+/- 14 days) for minimum 12 months in order to collect information on relapse and site of relapse

    Measured: 30 month

  7. quality of life

    Explorative analysis of health related quality of life, QoL at various time points throughout the study, to assess the QoL during and after induction therapy with gefitinib, after three cycles of chemotherapy with intercalated gefitinib including pre- and post surgery

    Measured: 30 month

  8. translational research

    To collect and store tumor tissue as well as plasma and serum samples for exploratory analyses of potential predictive markers, monitoring of biomarkers during and after treatment

    Measured: 30 month

  9. monitoring of epidermal growth factor receptor (EGFR) mutation status

    analysis of EGFR ctDNA in patient plasma; screening for EGFR mutation status (activating and resistance mutations especially T790M), monitoring of EGFR mutation status by means of Circulating tumor DNA (ctDNA) detection in patient plasma

    Measured: 30 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2014 (estimated)
  2. Study startNov 2015
  3. Primary completion28 Mar 2017
  4. Study completionJan 2018

Why it stopped: Due to low patient enrollment was stopped. Only one patient could be enrolled. 37 patients were pre-screened, but not into the inclusion criteria (wt-EGFR)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02326285
Sponsor's protocol ID
AIO-TRK-0214
Other IDs
2014-005595-28, IISR ESR-14-10598, 2014
Acronym
NeoIntercal
Status last verified
Jan 2018
First submitted
18 Dec 2014
Last updated
23 Jan 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Gefitinib, docetaxel and cisplatin in people with Non-squamous Non-small Cell Lung Cancer Stage II and Non-squamous Non-small Cell Lung Cancer Stage IIIA, run by AIO-Studien-gGmbH at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to low patient enrollment was stopped. Only one patient could be enrolled. 37 patients were pre-screened, but not into the inclusion criteria (wt-EGFR)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

pathologic complete remission rate (pCR rate) (time frame: 12 weeks (after 3 cycles and surgery) after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02326285.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.

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