Intercalated Administration of PamCis With Gefitinib or Placebo as First Line Lung Adenocarcinoma in Never Smokers

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by National Cancer Center, Korea
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Jin Soo Lee, National Cancer Center, Korea
ClinicalTrials.gov Identifier:
NCT01502202
First received: December 22, 2011
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

Intercalated administration of Iressa® (gefitinib) on days 5-18 of chemotherapy cycle improve the efficacy of Pemetrexed/platinum regimen given as first-line treatment for never-smokers with advanced (stage IIIB/IV) lung adenocarcinoma.


Condition Intervention Phase
Non Small Cell Lung Cancer
Adenocarcinoma
Drug: Gefitinib
Drug: Placebo
Drug: Pemetrexed plusCIsplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Placebo-controlled Phase II Study of Intercalated Administration of Pemetrexed/Cisplatin With Iressa® (Gefitinib) or Placebo as First-line Treatment of Stage IIIB/IV Lung Adenocarcinoma in Never-smokers

Resource links provided by NLM:


Further study details as provided by National Cancer Center, Korea:

Primary Outcome Measures:
  • To compare progression-free survival [ Time Frame: minimum 1-year follow-up ] [ Designated as safety issue: No ]

    from date of randomization until the date of first documented progression or death from any case.

    Assessed minimum 1 years.



Secondary Outcome Measures:
  • To compare objective response rate (CR+PR) [ Time Frame: minimum 1-year follow-up ] [ Designated as safety issue: No ]
    every 9 weeks until PD

  • To compare duration of response. [ Time Frame: minimum 1-year follow-up ] [ Designated as safety issue: No ]
  • To compare non progression rate (CR+PR+SD) at 16 weeks. [ Time Frame: at 16 weeks ] [ Designated as safety issue: No ]
  • To compare overall survival. [ Time Frame: minimum 1-year follow-up ] [ Designated as safety issue: No ]
  • To compare number of Grade 3/4 Adverse Events [ Time Frame: average up to 1 year ] [ Designated as safety issue: Yes ]
    Participants will be followed for the duration of chemotherapy. CTCAE version 4.0

  • To assess biomarker [ Time Frame: minimum 1-year follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment: 162
Study Start Date: March 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Study arm
Pemetrexed plus Cisplatin plus Gefitinib
Drug: Gefitinib
Gefitinib 250mg, per PO. daily, D 5-18 (during 14 days)
Other Name: AP-G
Drug: Pemetrexed plusCIsplatin
Pemetrexed 500mg/m2 on D1 plus Cisplatin 75mg/m2 on D1 every 3 weeks maximum 9 cycles
Other Name: Standard chemotherapy
Placebo Comparator: Placebo arm
Pemetrexed plus Cisplatin plus Placebo
Drug: Placebo
Placebo 1 tablet, per PO, Daily on D 5-18 (during 14 days)
Other Name: AP-P
Drug: Pemetrexed plusCIsplatin
Pemetrexed 500mg/m2 on D1 plus Cisplatin 75mg/m2 on D1 every 3 weeks maximum 9 cycles
Other Name: Standard chemotherapy

Detailed Description:

Investigators believe this PFS curve crossing-over in both IPASS and First-SIGNAL study is mainly due to early progression of EGFR mutation-negative tumors after gefitinib alone. Taken together with the FASTACT trial results, this PFS curve crossing-over may well be averted if effective chemotherapy is given together with gefitinib in a most optimum timing and sequence. Apparently, timing of EGFR-TKI administration within chemotherapy cycles is very critical, as shown in OSI 9774 trial.

In this placebo-controlled randomized phase II, Investigators propose to give gefitinib on days 5-18 of a 3-weekly chemotherapy cycle of pemetrexed/cisplatin to avoid any potential overlap of EGFR-TKI effects on chemotherapy or vice versa. Investigators would like to generate promising pilot data, which warrants a large phase III trial. Investigators hope to show that intercalated administration of Iressa® (gefitinib) and Pemetrexed/platinum regimen improves the outcome of never-smokers with advanced (stage IIIB/IV) lung adenocarcinoma.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of lung with or without BAC features; however, adenocarcinoma combined with other histology, such as small cell carcinoma or squamous carcinoma, is not allowed.
  2. Stage IIIB (not amenable for radical loco-regional therapy) or stage IV (metastatic) patients according to the 7th TNM staging system
  3. Age 18-75
  4. Never-smoking defined as not more than 100 cigarettes during the lifetime
  5. ECOG performance status of 0-2
  6. Good organ function
  7. The presence of CNS metastases is not considered as an exclusion criterion, provided that there is good control of the symptoms with corticosteroids
  8. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of the hospital. The only approved consent form is attached to this protocol

Exclusion Criteria:

  1. Patients with prior exposure to agents directed at the HER
  2. Patients with prior chemotherapy or therapy with systemic anti-tumour therapy for advanced disease.
  3. Lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome, or inability to take oral medication, or have active peptic ulcer disease.
  4. Known severe hypersensitivity to gefitinib or to any of the study drugs.
  5. Any evidence of clinically active interstitial lung disease
  6. Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort
  7. Prior invasive malignancies 3 years prior to study entry except adequately treated cutaneous basal cell carcinoma or uterine cervix in situ cancer
  8. As judged by the investigator, any evidence of severe or uncontrolled systemic disease
  9. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the study
  10. Treatment with a non-approved or investigational drug within 30 days before Day 1 of study treatment.
  11. Pregnancy or breast-feeding (women of child-bearing potential).
  12. Sexually active males and females (of childbearing potential) unwilling to practice acceptable methods of birth control
  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: NCT01502202

Contacts
Contact: Jin Soo Lee, M.D. PhD. +82-31-920-1501 jslee@ncc.re.kr
Contact: SUNG JIN YOON, RN +82-31-920-0405 jinijiniya@ncc.re.kr

Locations
Korea, Republic of
National Cancer Center Recruiting
Goyang-si, Gyenggido, Korea, Republic of, 410-769
Contact: Sung Jin Yoon, RN    +82-31-920-0405    jinijiniya@ncc.re.kr   
Contact: Jin Soo Lee, MD. Ph.D.    +82-31-920-1501    jslee@ncc.re.kr   
Sponsors and Collaborators
National Cancer Center, Korea
AstraZeneca
Investigators
Principal Investigator: Jin Soo Lee, M.D. PhD. National Cancer Center
  More Information

No publications provided

Responsible Party: Jin Soo Lee, Principal Investigator, National Cancer Center, Korea
ClinicalTrials.gov Identifier: NCT01502202     History of Changes
Other Study ID Numbers: NCCCTS-11-581
Study First Received: December 22, 2011
Last Updated: June 19, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by National Cancer Center, Korea:
lung adenocarcinoma
never smoker
1st line treatment
Intercalation administration
Gefitinib
never smokers

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pemetrexed
Gefitinib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014