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

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

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.

Study Overview

• Status: Unknown
• Conditions: Adenocarcinoma; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Gefitinib; Drug: Pemetrexed plusCIsplatin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 162
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jin Soo Lee, M.D. PhD.; Phone Number: +82-31-920-1501; Email: jslee@ncc.re.kr

Study Locations

• Korea, Republic of
  • Gyenggido
    • Goyang-si, Gyenggido, Korea, Republic of, 410-769
      • Recruiting
      • National Cancer Center
      • Contact: Jin Soo Lee, MD. Ph.D.; Phone Number: +82-31-920-1501; Email: jslee@ncc.re.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study arm; Pemetrexed plus Cisplatin plus Gefitinib	Drug: Gefitinib; Gefitinib 250mg, per PO. daily, D 5-18 (during 14 days); Other Names: AP-G; Drug: Pemetrexed plusCIsplatin; Pemetrexed 500mg/m2 on D1 plus Cisplatin 75mg/m2 on D1 every 3 weeks maximum 9 cycles; Other Names: Standard chemotherapy
Placebo Comparator: Placebo arm; Pemetrexed plus Cisplatin plus Placebo	Drug: Pemetrexed plusCIsplatin; Pemetrexed 500mg/m2 on D1 plus Cisplatin 75mg/m2 on D1 every 3 weeks maximum 9 cycles; Other Names: Standard chemotherapy; Drug: Placebo; Placebo 1 tablet, per PO, Daily on D 5-18 (during 14 days); Other Names: AP-P

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare progression-free survival	from date of randomization until the date of first documented progression or death from any case. Assessed minimum 1 years.	minimum 1-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare objective response rate (CR+PR)	every 9 weeks until PD	minimum 1-year follow-up
To compare duration of response.		minimum 1-year follow-up
To compare non progression rate (CR+PR+SD) at 16 weeks.		at 16 weeks
To compare overall survival.		minimum 1-year follow-up
To compare number of Grade 3/4 Adverse Events	Participants will be followed for the duration of chemotherapy. CTCAE version 4.0	average up to 1 year
To assess biomarker		minimum 1-year follow-up

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Jin Soo Lee, M.D. PhD., National Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: December 22, 2011
• First Submitted That Met QC Criteria: December 29, 2011
• First Posted (Estimate): December 30, 2011

Study Record Updates

• Last Update Posted (Estimate): June 20, 2012
• Last Update Submitted That Met QC Criteria: June 19, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: lung adenocarcinoma; Gefitinib; never smoker; 1st line treatment; never smokers; Intercalation administration
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Gefitinib; Pemetrexed
• Other Study ID Numbers: NCCCTS-11-581