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

• ClinicalTrials.gov Identifier: NCT01502202
• Recruitment Status: Unknown
• First Posted: December 30, 2011
• Last Update Posted: June 20, 2012
• Sponsor: National Cancer Center, Korea
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Jin Soo Lee, National Cancer Center, Korea

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer; Adenocarcinoma	Drug: Gefitinib; Drug: Placebo; Drug: Pemetrexed plusCIsplatin	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 162 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: March 2012
• Estimated Primary Completion Date: August 2014
• Estimated Study Completion Date: February 2015

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

1. To compare progression-free survival [ Time Frame: minimum 1-year follow-up ]

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

   Assessed minimum 1 years.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Jin Soo Lee, Principal Investigator, National Cancer Center, Korea
• ClinicalTrials.gov Identifier: NCT01502202
• Other Study ID Numbers: NCCCTS-11-581
• First Posted: December 30, 2011
• Last Update Posted: June 20, 2012
• Last Verified: June 2012

Keywords provided by Jin Soo Lee, National Cancer Center, Korea:

lung adenocarcinoma; never smoker; 1st line treatment; Intercalation administration; Gefitinib; never smokers

Additional relevant MeSH terms:

Adenocarcinoma; Adenocarcinoma of Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pemetrexed; Gefitinib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors