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

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01502202
• Other study ID #: NCCCTS-11-581
• Status: Recruiting
• Phase: Phase 2
• First received: December 22, 2011
• Last updated: June 19, 2012
• Start date: March 2012
• Est. completion date: February 2015

Study information

• Verified date: June 2012
• Source: National Cancer Center, Korea
• Contact: Jin Soo Lee, M.D. PhD.
• Phone: +82-31-920-1501
• Email: jslee[@]ncc.re.kr
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: February 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Gefitinib
Gefitinib 250mg, per PO. daily, D 5-18 (during 14 days)
• Placebo
Placebo 1 tablet, per PO, Daily on D 5-18 (during 14 days)
• Pemetrexed plusCIsplatin
Pemetrexed 500mg/m2 on D1 plus Cisplatin 75mg/m2 on D1 every 3 weeks maximum 9 cycles

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si	Gyenggido

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Center, Korea	AstraZeneca

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	To compare objective response rate (CR+PR)	every 9 weeks until PD	minimum 1-year follow-up	No
Secondary	To compare duration of response.		minimum 1-year follow-up	No
Secondary	To compare non progression rate (CR+PR+SD) at 16 weeks.		at 16 weeks	No
Secondary	To compare overall survival.		minimum 1-year follow-up	No
Secondary	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	Yes
Secondary	To assess biomarker		minimum 1-year follow-up	No