Irinotecan/Cisplatin, Potentially Curative Surgery With or Without Floxuridine, Followed by Capecitabine for Stomach and Gastro-esophageal Junction (GEJ) Cancers
Study Details
Study Description
Brief Summary
This study is to determine whether intraperitoneal (IP) Floxuridine is effective in the patients with advanced stomach or gastro-esophageal junction cancers in the treatment consisting of pre- and post-surgery chemotherapies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
A previous Phase-II trial conducted by the same principle investigator(s), utilizing preoperative chemotherapy and intraperitoneal consolidation, was conducted in patients with locally advanced, potentially resectable gastric cancer or cancer of the gastro-esophageal junction (GEJ), both staged as T3N0, T4N0, any TN1 or TN2 disease. The data suggest that for patients with locally advanced gastric or GEJ cancer, systemic induction therapy, curative surgery with high Ro resection rates, and IP adjuvant therapy, has acceptable toxicity and encouraging survival outcome. The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial has also shown that perioperative chemotherapy - chemotherapy given both before and after surgery - can provide a significant survival benefit.
The investigators hypothesize that adjuvant intraperitoneal salvage of cancer micrometastatic residues after surgery contributes to disease-free survival. The goal of this trial is to determine whether IP Floxuridine, added to adjuvant postoperative chemotherapy, prolongs patient's survival. This will be tested during the randomized open-label trial.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A-with IP Floxuridine Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral |
Drug: Irinotecan
Other Names:
Drug: Cisplatin
Procedure: Surgery
Drug: Floxuridine
Other Names:
Drug: Capecitabine
Other Names:
|
| Experimental: B-Without IP Floxuridine Same as Arm A except no postoperative IP treatment. |
Drug: Irinotecan
Other Names:
Drug: Cisplatin
Procedure: Surgery
Drug: Capecitabine
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With One-year Recurrence-free Survival [1 year]
This is defined as the patients who did not have recurrence of cancer at 1 year since the start of induction chemotherapy.
Secondary Outcome Measures
- Overall Survival Rate; Toxicity; Evaluation of Sites of Relapse of Failing Patients [every 4 months for the first 2 years, every 6 months for years 3 and 4, then every 12 months for up to 10 years]
Secondary outcome measure was not analyzed as study was terminated
Eligibility Criteria
Criteria
-
Only untreated patients with histologically documented gastric/GEJ adenocarcinoma, clinical American Joint Committee on Cancer (AJCC) stage grouping (11) IB-IV (Mo) by CT scan and laparoscopy/endoscopic ultrasound, are eligible. Excluded are patients in need of urgent surgery for gastro-intestinal obstruction, perforation or hemorrhage.
-
Both men and women >= 18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status 0-2, members of any ethnic group and minorities.
-
Patients without another invasive malignancy, with adequately treated basal cell or squamous cell skin cancer, free for 5 years or more of in-situ cervix cancer or other in-situ cancer.
-
Since immune deficiency increases the risk of terminal infections when aggravated by bone marrow suppressive therapy, patients must be without active or uncontrolled infection including HIV.
-
Patients without psychiatric disorders that may interfere with their consent and/or with protocol follow-up.
-
An adequate bone-marrow reserve (absolute neutrophil count >= 1,500/ mmL, thrombocytes
= 100,000 mmL, hemoglobin >= 9 gm/dL).
-
Preserved liver and renal function (total serum bilirubin <2 mg/dL, SGOT/SGPT =< 3x the upper limit of normal, alkaline phosphatase =< 3x the upper limit of normal, blood urea nitrogen (BUN) =< 30 mg/dL, serum creatinine concentration <1.5 mg/dL and creatinine clearance >= 50 mL/min) are required. Creatinine clearance should be normalized for 1.73 M^2 BSA. The prothrombin time, activated partial thromboplastin time, and thrombin time should be within the range of normal values.
-
Since chemotherapeutic agents to be used are known or suspected to be teratogenic or with other adverse effects, women must not be pregnant or breast-feeding. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. All patients of reproductive age may not participate unless they agree to use an effective medically acceptable contraceptive method.
-
Patients without diagnosed Gilbert's disease and bilirubin level >= 2.0 mg/dL, as these patients may have excessive CPT-11 toxicity.
-
No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil. Capecitabine (Xeloda) is contraindicated in patients with severe renal impairment, i.e., creatinine clearance below 30 mL/min, determined by Cockcroft-Gault equation shown on page 15 under (i) Renal impairment. In patients with moderate renal impairment (creatinine clearance 30-50 mL/min), which develops during the course of adjuvant treatment with Capecitabine, the drug is decreased to 75% of the starting dose.
-
Patients should be without any severe concurrent disease, such as cardiac condition not responding to medication, myocardial infarction within the last 12 months, active infection or uncontrolled pulmonary disease, or any other disease which in judgment of the investigator would make the patient inappropriate for entry into this study.
-
Patients who signed written informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Norris Cancer Center | Los Angeles | California | United States | 90033 |
| 2 | Bellevue Hospital | New York | New York | United States | 10016 |
| 3 | NYU Cancer Center | New York | New York | United States | 10016 |
Sponsors and Collaborators
- NYU Langone Health
Investigators
- Principal Investigator: Franco Muggia, MD, NYU Langone Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 07-837
- NYU 05-20
Study Results
Participant Flow
| Recruitment Details | Between March 2008 and May 2010 eight patient were enrolled to the study from New York University Langone Medical Center and University of South California Cancer Center. |
|---|---|
| Pre-assignment Detail | Patients were randomized to Arm A or Arm B after the response evaluation of the induction treatment. One patient was not randomized due to progression of disease before surgery and was taken off the protocol treatment. |
| Arm/Group Title | A-with IP Floxuridine | B-Without IP Floxuridine | Induction Treartment Only |
|---|---|---|---|
| Arm/Group Description | Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral | Same as Arm A except no postoperative IP treatment. | This is not a treatment cohort specified in the protocol. The patient in this group was not randomized to Arm A or Arm B due to disease progression before surgery and was taken off the study. |
| Period Title: Overall Study | |||
| STARTED | 4 | 3 | 1 |
| COMPLETED | 1 | 1 | 1 |
| NOT COMPLETED | 3 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | A-with IP Floxuridine | B-Without IP Floxuridine | Induction Treatment Only | Total |
|---|---|---|---|---|
| Arm/Group Description | Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral | Same as Arm A except no postoperative IP treatment. | This is not a treatment cohort specified in the protocol. The patient in this group was not randomized to Arm A or Arm B due to disease progression before surgery and was taken off the study. | Total of all reporting groups |
| Overall Participants | 4 | 3 | 1 | 8 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
4
100%
|
3
100%
|
1
100%
|
8
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
53.8
(12.8)
|
54.3
(3.2)
|
60
(0)
|
54.8
(8.8)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
25%
|
0
0%
|
0
0%
|
1
12.5%
|
| Male |
3
75%
|
3
100%
|
1
100%
|
7
87.5%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
4
100%
|
3
100%
|
1
100%
|
8
100%
|
Outcome Measures
| Title | Number of Patients With One-year Recurrence-free Survival |
|---|---|
| Description | This is defined as the patients who did not have recurrence of cancer at 1 year since the start of induction chemotherapy. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Based on intent-to-treat population. |
| Arm/Group Title | A-with IP Floxuridine | B-Without IP Floxuridine |
|---|---|---|
| Arm/Group Description | Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral | Same as Arm A except no postoperative IP treatment. |
| Measure Participants | 4 | 3 |
| Number [participants] |
3
75%
|
2
66.7%
|
| Title | Overall Survival Rate; Toxicity; Evaluation of Sites of Relapse of Failing Patients |
|---|---|
| Description | Secondary outcome measure was not analyzed as study was terminated |
| Time Frame | every 4 months for the first 2 years, every 6 months for years 3 and 4, then every 12 months for up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Secondary outcome measure was not analyzed as study was terminated |
| Arm/Group Title | A-with IP Floxuridine | B-Without IP Floxuridine | Induction Treatment Only |
|---|---|---|---|
| Arm/Group Description | Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral | Same as Arm A except no postoperative IP treatment. | This is not a treatment cohort specified in the protocol. The patient in this group was not randomized to Arm A or Arm B due to disease progression before surgery and was taken off the study. |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | The adverse events were followed during the whole treatment phase, about 1 year. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | A-with IP Floxuridine | B-Without IP Floxuridine | ||
| Arm/Group Description | Induction treatment: Cisplatin 25 mg/m^2 and Irinotecan 75 mg/m^2 once a week for 4 weeks, both intravenous; Two weeks without treatment; Repeat the course once. Re-evaluation, surgery if complete response, partial response or stable disease, or off the protocol if progression of disease. Randomization Surgery. Postoperative IP treatment: Day 1,2,3: Floxuridine 3 gm/day, IP; Day 3: Cisplatin 60 mg/m^2, IP; 2 weeks without treatment; repeat the course once Postoperative systemic treatment: courses 1-9: Capecitabine 2,000 mg/m^2/day x14 every 3 weeks/course, Oral | Same as Arm A except no postoperative IP treatment. | ||
All Cause Mortality |
||||
| A-with IP Floxuridine | B-Without IP Floxuridine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| A-with IP Floxuridine | B-Without IP Floxuridine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 2/3 (66.7%) | ||
| Blood and lymphatic system disorders | ||||
| Neutrophils/Granulocytes (Anc/Agc) | 0/4 (0%) | 1/3 (33.3%) | ||
| Infections and infestations | ||||
| Infection With Normal Anc Or Grade 1 Or 2 Neutrophils | 0/4 (0%) | 1/3 (33.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| A-with IP Floxuridine | B-Without IP Floxuridine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 3/3 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Blood/Bone Marrow - Other (Specify, __) | 1/4 (25%) | 0/3 (0%) | ||
| Hemoglobin | 4/4 (100%) | 1/3 (33.3%) | ||
| Neutrophils/Granulocytes (Anc/Agc) | 3/4 (75%) | 1/3 (33.3%) | ||
| Platelets | 1/4 (25%) | 0/3 (0%) | ||
| Cardiac disorders | ||||
| Palpitations | 1/4 (25%) | 0/3 (0%) | ||
| Gastrointestinal disorders | ||||
| Anorexia | 2/4 (50%) | 1/3 (33.3%) | ||
| Constipation | 2/4 (50%) | 0/3 (0%) | ||
| Diarrhea | 4/4 (100%) | 2/3 (66.7%) | ||
| Distension/Bloating, Abdominal | 2/4 (50%) | 0/3 (0%) | ||
| Dysphagia (Difficulty Swallowing) | 1/4 (25%) | 0/3 (0%) | ||
| Heartburn/Dyspepsia | 1/4 (25%) | 1/3 (33.3%) | ||
| Taste Alteration (Dysgeusia) | 1/4 (25%) | 0/3 (0%) | ||
| Vomiting | 3/4 (75%) | 1/3 (33.3%) | ||
| General disorders | ||||
| Fatigue (Asthenia, Lethargy, Malaise) | 4/4 (100%) | 1/3 (33.3%) | ||
| Insomnia | 2/4 (50%) | 0/3 (0%) | ||
| Weight Loss | 2/4 (50%) | 0/3 (0%) | ||
| Nausea | 4/4 (100%) | 1/3 (33.3%) | ||
| Pain | 3/4 (75%) | 0/3 (0%) | ||
| Investigations | ||||
| Alt, Sgpt (Serum Glutamic Pyruvic Transaminase) | 1/4 (25%) | 0/3 (0%) | ||
| Ast, Sgot(Serum Glutamic Oxaloacetic Transaminase) | 1/4 (25%) | 0/3 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Glucose, Serum-High (Hyperglycemia) | 2/4 (50%) | 0/3 (0%) | ||
| Nervous system disorders | ||||
| Dizziness | 2/4 (50%) | 0/3 (0%) | ||
| Mood Alteration | 1/4 (25%) | 0/3 (0%) | ||
| Neurology - Other (Specify, __) | 2/4 (50%) | 0/3 (0%) | ||
| Neuropathy: Sensory | 1/4 (25%) | 1/3 (33.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Hair Loss/Alopecia (Scalp Or Body) | 2/4 (50%) | 0/3 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Franco Muggia, MD |
|---|---|
| Organization | NYU Cancer Institute |
| Phone | 212-263-6485 |
| franco.muggia@nyumc.org |
- 07-837
- NYU 05-20