Afatinib, Paclitaxel, 2nd Line, Advanced Gastric Cancer

Study Overview
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Brief Summary
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For the gastric cancer, paclitaxel is recommended as salvage standard treatment. Afatinib is a novel, potent, small ErbB family blocker that covalently binds and irreversibly blocks signaling through activated EGFR, HER2 and ErbB4 receptors, as well as the transphosphorylation of ErbB3. The investigators suggest a randomized phase II trial of afatinib plus weekly taxol(paclitaxel) for previously treated EGFR positive gastric cancer patients. The aim of current trial is to evaluate the antitumor efficacy of afatinib for target enriched patients in gastric cancer.

Official Title
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An Open-label, Multicenter Phase II Study of Afatinib Plus Weekly Taxol as Second Line Treatment for Advanced/Recurrent Gastric and Gastroesophageal Junction Cancer

Conditions
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Gastric Cancer, Gastroesophageal Junction Cancer

Intervention / Treatment
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* Drug: afatinib
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced or metastatic gastric cancer and gastroesophageal junction cancer EGFR 2+ or 3+ expression (immunohistochemistry) ECOG performance status of 0 to 1 Male or female; ≥ 19 years of age Documented disease progression after one prior therapy, in locally advanced or metastatic setting patients received last adjuvant chemotherapy less than six months can be enrolled into this study Her2 positive patients must be progressed after prior trastuzumab based chemotherapy Subjects with measurable lesion (using RECIST 1.1 criteria) Subjects who meet the following criteria: Absolute neutrophil count (ANC) ≥ 1000 /µL (*ANC = Neutrophil segs ＋ Neutrophil bands) Platelet count ≥ 80,000/ µL Serum creatinine < 1.5 x upper limit of normal (ULN) or Creatinine clearance ≥50 mL/min using Cockcroft, Gault method AST (SGOT) and ALT (SGPT) : 3 x upper limit of normal (ULN) (If there is Liver Metastasis : 5 x upper limit of normal (ULN)) Total bilirubin : 1.5 x upper limit of normal (ULN) Provision of written informed consent prior to any study procedure Exclusion Criteria: Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy. Any previous chemotherapy or immunotherapy within 2 weeks Any major operation or irradiation within 4 weeks of baseline disease assessment Two or more previous systemic cytotoxic chemotherapy (adjuvant chemotherapy is not counted) Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug Previously taxol(paclitaxel)-exposed patients Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma, thyroid cancer or cervical cancer in situ. Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension) Pregnant or lactating female Patients with contraindicated medication History of interstitial lung disease (ILD) or presence of ILD on chest X-ray Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: afatinib plus paclitaxel<br>afatinib plus paclitaxel | Drug: afatinib<br>* Afatinib 40mg daily oral administration<br>Drug: paclitaxel<br>* Paclitaxel 80mg/m2 IV weekly (day 1,8,15)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare progression free survival as measured by RECIST 1.1 | To identify antitumor activity of afatinib plus weekly taxol(paclitaxel) and explore predictive biomarker | Every 6 weeks until progression, an expected average of 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| antitumor efficacy as measured by RECIST 1.1 |  | every 6 weeks until progression, an expected average of 10 months | 
| safety as measured by CTCAE |  | every 3 weeks until progression, an expected average of 10 months |