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

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:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium Gefitinib

U.S. FDA Resources

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:

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.
Stage IIIB (not amenable for radical loco-regional therapy) or stage IV (metastatic) patients according to the 7th TNM staging system
Age 18-75
Never-smoking defined as not more than 100 cigarettes during the lifetime
ECOG performance status of 0-2
Good organ function
The presence of CNS metastases is not considered as an exclusion criterion, provided that there is good control of the symptoms with corticosteroids
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:

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

Contacts and Locations

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:

Adenocarcinoma
Adenocarcinoma, Mucinous
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases

Respiratory Tract Diseases
Pemetrexed
Gefitinib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013