Pemetrexed Plus Cisplatin as First-Line Treatment in Stage IV or Recurrence of Gastric Cancer

Study Overview
=================
Brief Summary
-----------------
Study H3E-MW- S108 is a multicenter, single arm, open-label Phase 2 study to determine the response rate of pemetrexed plus cisplatin in patients with Stage IV gastric cancer, not amenable to curative surgery, or recurrence after prior surgery, who have had no prior chemotherapy. It was planned to enroll approximately 50 patients who qualified for tumor response population.

Official Title
-----------------
Phase 2 Study of ALIMTA® (Pemetrexed) Plus Cisplatin as First-Line Treatment of Gastric Cancer

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Drug: pemetrexed
* Drug: cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of adenocarcinoma of the gastric. Stage IV disease, not amenable to curative surgery, or disease recurrence after prior surgery. Disease status must be that of measurable disease with presence of at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. In bidimensionally measurable lesions the longest diameter should be selected for measurement. Tumor lesions in areas of prior radiation therapy may be included only if they were clearly progressing. If only a single lesion is present in a patient who had prior therapy for gastric adenocarcinoma, the neoplastic nature of the lesion should be confirmed by cytology and/or histology. Ultrasound and clinical examination are not allowed for assessment of measurable disease. Elevation of tumor markers, pleural or pericardial effusion, ascites, bone lesions, cystic lesions, or carcinomatous lymphangitis pulmonis/cutis is defined as not being measurable. Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Scale. Estimated life expectancy of at least 12 weeks. No prior chemotherapy or radiotherapy. Patient compliance and geographic proximity that allow adequate follow-up. Adequate organ function including the following: Bone marrow: absolute neutrophil count 1.5 x 10 to the ninth power/liter (L), platelets 100 x 10 to the ninth power/L, hemoglobin >=9 grams per deciliter (g/dL). Hepatic: bilirubin <=1.5 x upper limit of normal (ULN); alkaline phosphatase, aspartate transaminase and alanine transaminase <=3.0 x ULN. Renal: Calculated creatinine clearance >=45 milliliters (ml)/minute. Men or women, age 18 to 70 years. For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment and must not be breast-feeding. For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after the treatment period. Signed informed consent from patient. Exclusion Criteria: Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Concurrent administration of any other tumor therapy. Active infection. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator. Pregnancy. Breast-feeding. History of significant neurological or mental disorder, including seizures or dementia. Have had a prior malignancy other than gastric cancer, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence. Patients with a history of low grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years previously. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs 2 days before, the day of, and 2 days after the dose of pemetrexed plus cisplatin. If a patient is taking a nonsteroidal anti-inflammatory drug (NSAID) or salicylate with a long half-life it should not be taken 5 days before, the day of, and 2 days after the dose of pemetrexed plus cisplatin. Clinically significant ascites or pleural effusion that is apparent at clinical examination and cannot be controlled by drainage or other procedures prior to study enrollment. NOTE: Small effusions noted on computed tomography (CT) scan do not exclude the patient from study enrollment. Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone. Known or suspected brain metastasis. Patients who have clinical signs or symptoms that are suspicious of brain metastasis must have a pretreatment CT or magnetic resonance imaging (MRI) of the brain. A patient with documented brain metastasis, at the time of consideration for study entry or in the past, will be excluded from entering in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed + Cisplatin<br> | Drug: pemetrexed<br>* 700 milligrams/meters squared (mg/m2), intravenous (IV), every 21 days x 6 cycles<br>* Other names: Alimta;Drug: cisplatin<br>* 75 mg/m2, IV, every 21 days x 6 cycles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (Objective Response Rate) | Tumor responder is defined as participants exhibiting a best overall study response of complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in sum of longest diameter of target lesions). Non-responders are those who did not meet the above criteria. | Baseline to time of response up to six or eight 21-day cycles of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Measured from the time of first documentation of CR or PR (whichever status is first recorded) until the date of time to disease progression. | Time of response to progressive disease up to six or eight 21-day cycles of treatment; maximum duration of study follow-up was 17.4 months | 
| Progression Free Survival (PFS) | Defined as time from baseline to the date of disease progression or death on study, whichever occurs first. The PFS 1 definition from the United States Food and Drug Administration (FDA) draft guidance on clinical endpoints was used (FDA 2005). | Baseline to measured progressive disease or death up to six or eight 21-day cycles of treatment; maximum duration of study follow-up was 17.4 months | 
| Overall Survival | Defined as the time from baseline to date of death due to any cause. Survival time is censored at the date of last contact for patients who are still alive or lost to follow up. | Baseline to date of death from any cause up to six or eight 21-day cycles of treatment; maximum duration of study follow-up was 17.4 months | 
| Number of Participants With Pharmacology Toxicity - Grade 3 or 4 Laboratory Toxicity Possibly Related to Study Therapy | Common toxicity criteria (CTC) Grade 3 (severe) or 4 (life-threatening or disabling) laboratory toxicity possibly related to study therapy. A grading (severity) scale is provided for each event term. Grades range from 0 (none) to 5 (death). | Baseline through six or eight 21-day cycles of treatment, up to 30 days after study drug discontinuation | 
| Number of Participants With Pharmacology Toxicity - Grade 3 or 4 Non-Laboratory Toxicity Possibly Related to Study Therapy | Common toxicity criteria (CTC) Grade 3 (severe) or 4 (life-threatening or disabling) non-laboratory toxicity possibly related to study therapy. A grading (severity) scale is provided for each event term. Grades range from 0 (none) to 5 (death). | Baseline through six or eight 21-day cycles of treatment, up to 30 days after study drug discontinuation | 
| Number of Participants Who Died During the Study |  | During study drug therapy up to six or eight 21-day cycles or treatment; maximum duration of study follow-up was 17.4 months |