Pemetrexed vs Pemetrexed Plus Cisplatin in EGFR-mutant NSCLC Patients After First Line EGFR-TKIs Failure

NCT02725918 | Unknown Phase 2

• 1 other identifier: CTONG1510
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a prospective, multi-center, open-label, randomized, and controlled phase II clinical trial. The investigators hope to figure out the better chemotherapy regimen for the post-EGFR-TKI failure setting. The primary objective of this trial is to compare progression-free survival without grade 4 (G4PFS) toxicities between pemetrexed-cisplatin and single-agent pemetrexed treatment arms. The trial will include stage IIIB/IV EGFR mutation positive NSCLC patients who got disease progression after front-line EGFR TKI treatment.Eligible patients will be randomized to 2 arms. Patients in arm A will receive 4 cycles of cisplatin (75 mg/m2, d1) and pemetrexed (500 mg/m2, d1) every 3 weeks, those without disease progression (PD) and being tolerable judged by investigator will continue single-agent pemetrexed (500 mg/m2, d1) every 3 weeks as maintenance until progression or intolerable toxicities. Patients in arm B will receive pemetrexed (500 mg/m2, d1) every 3 weeks until PD or intolerable toxicities.

Conditions

Non-small Cell Lung Cancer

Keywords

NSCLC; EGFR-TKI failure; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival without grade 4 (G4PFS)

  From the date of randomization to the earliest occurrence of the first of grade 4 adverse events (AEs), disease progression, or death from any cause, regardless of whether or not the event leads to discontinuation,assessed up to 4 months.

Secondary Outcomes (3)

• Progression free survival (PFS)

  From the date of randomization to the first date of documented objective progression disease or of death from any cause,assessed up to 6 months.

• Overall survival (OS)

  From the date of randomization to the date of death from any cause,assessed up to 12 months.

• Overall response rate (ORR)

  From randomization to date of objective disease progression,assessed up to 6 months.

Study Arms (2)

Pem mono

EXPERIMENTAL

Patients in arm B will receive pemetrexed (500 mg/m2, d1) every 3 weeks until PD or intolerable toxicities.

Drug: Pemetrexed

Pem+Cis

ACTIVE COMPARATOR

Patients in arm A will receive 4 cycles of cisplatin (75 mg/m2, d1) and pemetrexed (500 mg/m2, d1) every 3 weeks, those without disease progression (PD) and being tolerable judged by investigator will continue single-agent pemetrexed (500 mg/m2, d1) every 3 weeks as maintenance until progression or intolerable toxicities.

Drug: Pemetrexed; Drug: Cisplatin

Interventions

Pemetrexed DRUG

500 mg/m2,iv,d1,q3w,until PD

Also known as: Alimta，pemetrexed disodium

Pem mono; Pem+Cis

Cisplatin DRUG

75 mg/m2,iv,d1,q3w,×4 cycles

Also known as: DDP，platinol

Pem+Cis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent must be signed.
• Age of ≥18 and \< 75 years old.
• Performance status (PS) 0 - 2 on the Eastern Cooperative Oncology Group (ECOG) Scale.
• Histologically confirmed stage IIIB/IV advanced NSCLC harboring activating EGFR mutation.
• Chemotherapy-naïve for advanced disease.
• Acquired resistance is measured according to the Jackman criteria. Achieved complete remission (CR)/partial remission (PR)≥4 months or stable disease (SD)\>6 months with first-line EGFR TKIs (Gefitinib or Erlotinib or Icotinib) for advanced NSCLC.
• Disease progression(RECIST) \<4 weeks prior to study randomization.
• Adequate organ function including the following:
• Bone marrow: absolute neutrophil count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L hemoglobin ≥9 g/dL.
• Hepatic: total bilirubin ≤1.5 times the upper limit of normal (ULN), liver transaminases: aspartate transaminase (AST or SGOT) and alanine transaminase (ALT or SGPT) ≤2.5 times ULN. AST and ALT ≤ 5 x ULN may be included only if Patient has liver metastasis.
• Renal: calculated creatinine clearance ≥45 mL/min (using the standard Cockcroft-Gault formula).
• Patients have resolution to \<Grade 2 by the CTCAE (Version 4.0), of all clinically significant toxic effects of prior anti-cancer therapy (with the exception of rash and alopecia).
• Patients with stable central nervous system (CNS) metastasis successfully treated with local therapy, or with asymptomatic CNS metastasis are eligible. Treated stable CNS metastases are allowed; the patient must be stable after radiotherapy for ≥2 weeks and off of corticosteroids for ≥1 week.
• At least one measurable lesion as defined by RECIST 1.1 criteria.
• Previous palliative radiation therapy is allowed, but limited in \<25% of the bone marrow and must not have included whole pelvis radiation. Patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed one month before study entry. Radiotherapy should not be administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented.

You may not qualify if:

• Patient got disease relapsed within 12 months after post-operative adjuvant chemotherapy, thereafter got failure from subsequent EGFR-TKI treatment cannot be enrolled.
• History of another malignancy within the last 5 years except cured carcinoma in-situ of uterine cervix, cured basal cell carcinoma of skin and superficial bladder tumors \[Ta, Tis \& T1\].
• Any unstable systemic disease (including active infection, hepatic, renal or metabolic disease) or serious concomitant disorders that will compromise the safety of the patient, or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Significant cardiovascular event: congestive heart failure \>New York Heart Association (NYHA) class 2; unstable angina, active coronary artery disease (myocardial infarction more than 1 year prior to study entry is allowed); serious cardiac arrhythmia requiring anti-arrythmic therapy ( beta blockers or digoxin are permitted) or uncontrolled hypertension.
• History of significant neurological or mental disorder, including seizures or dementia.
• Incision from operation has not healed before the start of study treatment (Small incision for biopsy is eligible.)
• Presence of clinically uncontrollable third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
• Inability or unwillingness to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) from 2 days before to 2 days after administration of pemetrexed. If a patient is taking an NSAID (including Cox-2 inhibitors) or salicylate with a long half-life (e.g. naproxen, piroxicam, diflusinal, nabumetone, rofecoxib, or celecoxib), it should not be taken from 5 days before to 2 days after the administration of pemetrexed.
• Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone.
• Inability to comply with protocol or study procedures.
• Concurrent use of any other anti-tumor therapy during study.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead

Study Sites (1)

Guangdong Lung cancer institute

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (4)

• Zeng Z, Yan HH, Zhang XC, Zhong WZ, He YY, Guan JL, Niu FY, Xie Z, Huang YS, Xu CR, Dong S, Wu YL. Reduced chemotherapy sensitivity in EGFR-mutant lung cancer patient with frontline EGFR tyrosine kinase inhibitor. Lung Cancer. 2014 Nov;86(2):219-24. doi: 10.1016/j.lungcan.2014.09.008. Epub 2014 Sep 18.

  PMID: 25263853 RESULT

• Tseng JS, Yang TY, Chen KC, Hsu KH, Yu CJ, Liao WY, Tsai CR, Tsai MH, Yu SL, Su KY, Chen JJ, Chen HY, Chang GC. Prior EGFR tyrosine-kinase inhibitor therapy did not influence the efficacy of subsequent pemetrexed plus platinum in advanced chemonaive patients with EGFR-mutant lung adenocarcinoma. Onco Targets Ther. 2014 May 23;7:799-805. doi: 10.2147/OTT.S62639. eCollection 2014.

  PMID: 24920920 RESULT

• Yang JJ, Chen HJ, Yan HH, Zhang XC, Zhou Q, Su J, Wang Z, Xu CR, Huang YS, Wang BC, Yang XN, Zhong WZ, Nie Q, Liao RQ, Jiang BY, Dong S, Wu YL. Clinical modes of EGFR tyrosine kinase inhibitor failure and subsequent management in advanced non-small cell lung cancer. Lung Cancer. 2013 Jan;79(1):33-9. doi: 10.1016/j.lungcan.2012.09.016. Epub 2012 Oct 15.

  PMID: 23079155 RESULT

• Zinner RG, Obasaju CK, Spigel DR, Weaver RW, Beck JT, Waterhouse DM, Modiano MR, Hrinczenko B, Nikolinakos PG, Liu J, Koustenis AG, Winfree KB, Melemed SA, Guba SC, Ortuzar WI, Desaiah D, Treat JA, Govindan R, Ross HJ. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2015 Jan;10(1):134-42. doi: 10.1097/JTO.0000000000000366.

  PMID: 25371077 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yi long Wu

  Guangzhou lung cancer institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qing Zhou, MD

CONTACT

86 13544561166; gzzhouqing@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: April 1, 2016
• Study Start: April 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: February 1, 2021
• Last Updated: February 12, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)