Genius Study Study to Compare Efficacy and Safety of Gefitinib/ Pemetrexed With Pemetrexed Alone as Maintenance Therapy in Patients With Stage IV EGFR Mutation Negative or T790M Single Mutation Who Respond to Pemetrexed/ Platinum as First-line Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Taiwan University Hospital
Taichung Veterans General Hospital
China Medical University Hospital
Dalin Tzu Chi General Hospital
Tri-Service General Hospital
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov Identifier:
NCT01579630
First received: April 12, 2012
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

The study aims to randomize 52 patients with advanced (Stage IV) EGFR mutation negative nonsquamous non-small cell lung cancer (NSCLC) who respond (CR/PR/SD) to 4 cycles of pemetrexed / cisplatin or pemetrexed/carboplatin as first-line therapy. In order to achieve that, approximately 144 treatment naïve patients with advanced nonsquamous NSCLC need to be enrolled from around 6 investigational sites in Taiwan that have expertise in lung cancer diagnosis.


Condition Intervention Phase
NSCLC
Drug: Pemetrexed 500mg/m2 iv
Drug: Pemetrexed 500mg/m2 iv and Gefitinib 250 mg
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Randomized, Multicenter, Phase II Study to Compare Efficacy and Safety of Gefitinib/ Pemetrexed With Pemetrexed Alone as Maintenance Therapy in Patients With Advanced (Stage IV) EGFR Mutation Negative or T790M Single Mutation Nonsquamous NSCLC Who Respond to 4 Cycles of Pemetrexed/ Platinum as First-line Therapy

Resource links provided by NLM:


Further study details as provided by Taipei Veterans General Hospital, Taiwan:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: up to 4 months ] [ Designated as safety issue: No ]
    Progression of disease will be calculated from the tumour measurements collected at each tumour assessment per the RECIST (V1.1) criteria and/or the date of patient death.


Secondary Outcome Measures:
  • Overall objective tumour response [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    The RECIST (V1.1) criteria will be used to assess objective tumour response. Details of target and non-target lesions will be collected on the appropriate CRF pages and used to calculate tumour response. Post-baseline tumour evaluations should use the same modality (CT scan or magnetic resonance imaging [MRI]) as used at baseline and should preferably be undertaken at the same institution.


Enrollment: 52
Study Start Date: March 2011
Estimated Study Completion Date: June 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pemetrexed 500mg/m2 iv Drug: Pemetrexed 500mg/m2 iv
EGFR mutation negative patients who continuously respond (CR, PR or SD) to the 4th cycle of pemetrexed/ cisplatin or pemetrexed/carboplatin will be randomized in a 1:1 ratio to receive either gefitinib/ pemetrexed, or pemetrexed alone as maintenance therapy until progression of disease (PD) or discontinuation of treatment for other reasons.
Experimental: Pemetrexed 500 mg/m2 i.v. and Gefitinib 250 mg Drug: Pemetrexed 500mg/m2 iv and Gefitinib 250 mg
EGFR mutation negative patients who continuously respond (CR, PR or SD) to the 4th cycle of pemetrexed/ cisplatin or pemetrexed/carboplatin will be randomized in a 1:1 ratio to receive either gefitinib/ pemetrexed, or pemetrexed alone as maintenance therapy until progression of disease (PD) or discontinuation of treatment for other reasons.

Detailed Description:

The hypothesis tested in this study is that gefitinib / pemetrexed as maintenance therapy in patients with advanced (stage IV) EGFR mutation negative nonsquamous NSCLC who respond to 4 cycles of pemetrexed / cisplatin or pemetrexed/carboplatin as first-line therapy will achieve longer PFS than pemetrexed alone. We assume a median PFS of 4 months for patients receiving pemetrexed alone and the hazard ratio of pemetrexed alone compared to gefitinib/pemetrexed would be 0.42. It also indicates that the median PFS in gefitinib/pemetrexed group will be approximately 9.52 months. This is a 2-arm study in a 1:1 randomisation. Assuming an uniform accrual of 12-month with an addition of 12-month follow-up period, the total evaluable number of patients will be 52 to achieve a power of 80% and one-sided significance level of 0.025 to detect such difference between gefitinib/pemetrexed and pemetrexed alone.

Assuming 60% of patients respond (CR/PR/SD) to 4 cycles of pemetrexed/gefitinib, and among them 60% are EGFR mutation negative, 144 patients need to be enrolled to receive 4 cycles of pemetrexed/cisplatin or pemetrexed/carboplatin as first-line therapy.

Besides, the result of anaplastic lymphoma kinase gene (ALK) mutation will be retrospectively collected if the mutation is available for study patients during the study period.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria summary

  1. Provision of written informed consent
  2. Patients age 20 years or older
  3. Histological or cytological confirmed advanced (stageIV) nonsquamous NSCLC
  4. NSCLC treatment naïve(except patients who have pre- and post-operative non-platinum based adjuvant chemotherapy greater than 6 months prior to enrolment can be enrolled.)
  5. Measurable disease according to RECIST (Version 1.1) criteria
  6. World Health Organization (WHO) performance status (PS) of 0 to 1
  7. Provision of cancer tissue sample for mutation testing or the result of EGFR mutation test is negative (single T790M mutation positive patients can also be enrolled)

Exclusion Criteria summary

  1. Newly diagnosed Central Nervous System (CNS) metastases that have not yet been definitively treated with surgery and/or radiation.
  2. Known severe hypersensitivity to gefitinib, pemetrexed, cisplatin and carboplatin or any of the excipients of these products
  3. Known severe hypersensitivity to pre-medications required for treatment with pemetrexed / cisplatin or pemetrexed/carboplatin doublet chemotherapy
  4. Absolute neutrophil counts (ANC) less than 2.0 x 109/L (2,000/mm3), platelets less than 100 x 109/L (100,000/mm3) or haemoglobin less than 10 g/dl
  5. Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline
  6. Serum bilirubin is greater than 1.5 times the upper limit of reference range
  7. Serum creatinine is greater than 1.5 times the ULRR
  8. Unable to tolerate pemetrexed/ cisplatin or pemetrexed/carboplatin doublet chemotherapy, as judged by the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01579630

Locations
Taiwan
Veterans General Hospital -Taipei
Taipei, Taiwan, 112
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
National Taiwan University Hospital
Taichung Veterans General Hospital
China Medical University Hospital
Dalin Tzu Chi General Hospital
Tri-Service General Hospital
  More Information

No publications provided

Responsible Party: vghtpe user, Principal Investigator; Chief of Section of Thoracic Oncology of the Chest Department, Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov Identifier: NCT01579630     History of Changes
Other Study ID Numbers: D7913L00077
Study First Received: April 12, 2012
Last Updated: April 3, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by Taipei Veterans General Hospital, Taiwan:
NSCLC
Nonsquamous
Maintenance therapy

Additional relevant MeSH terms:
Gefitinib
Pemetrexed
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014