Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00084617
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Arm: 1
• Duration (Months): 57
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Drugs used in chemotherapy, such as oxaliplatin, irinotecan, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one chemotherapy drug may kill more tumor cells. This phase II trial is studying how well giving oxaliplatin together with irinotecan and capecitabine works in treating patients with metastatic or inoperable locally advanced gastric cancer or gastroesophageal junction adenocarcinoma (cancer).

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer	Drug: oxaliplatin; Drug: irinotecan hydrochloride; Drug: capecitabine	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the total response rate of the oxaliplatin, irinotecan and capecitabine drug combination in advanced gastric/esophageal junction carcinoma.

2. To assess the duration of total responses of the oxaliplatin, irinotecan and capecitabine drug combination in advanced gastric/esophageal junction carcinoma.

OUTLINE: This is a multicenter study.

Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Patients are followed annually.

PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study within 18 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Oxaliplatin, Irinotecan, and Capecitabine in Advanced Gastric/Gastroesophageal Junction Carcinoma
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (oxaliplatin, irinotecan, capecitabine) Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.	Drug: oxaliplatin; Given IV; Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP ; Drug: irinotecan hydrochloride; Given IV; Other Names: Campto Camptosar CPT-11 irinotecan U-101440E ; Drug: capecitabine; Given orally; Other Names: CAPE Ro 09-1978/000 Xeloda

Outcome Measures

Primary Outcome Measures

1. Response Rates (RR) in Metastatic Gastric/GE Junction Tumors [at 12 weeks (after 2 cycles of treatment)]

   Response is defined as the number of patients with a CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of the target lesions or appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage or increase of target lesions.

Secondary Outcome Measures

1. Complete Response (CR) and Partial Response (PR) Duration [at 40 months from study activation]

   The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

2. Overall Survival [at 40 months from study activation]

   Length of time patients survived after treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. Patients must have metastatic or inoperable locally advanced disease; GE Junction tumor location should be documented in the patient's medical record chart using the Siewert classification below:

• Type I: Adenocarcinoma of the distal esophagus which usually arises from an area with specialized intestinal metaplasia of the esophagus and which may infiltrate the GE junction from above Type II: True carcinoma of the cardia arising from the cardiac epithelium or short segments with intestinal metaplasia at the GE junction Type III: Subcardial gastric carcinoma which infiltrates the GE junction and distal esophagus from below

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• No prior chemotherapy for metastatic or recurrent disease is allowed; one course of neoadjuvant chemotherapy and/or adjuvant chemotherapy with or without radiation therapy as primary treatment is acceptable; at least 4 weeks must have elapsed since prior radiation therapy; patients must have been off previous anti-cancer therapy for at least 4 weeks

• Life expectancy of >= 12 weeks

• ECOG performance status 0-2

• Hemoglobin >= 9.5 g/dL

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin =< 1.5 mg/dL

• Creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• The effects of oxaliplatin, irinotecan, and capecitabine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because these drugs are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients may not be receiving any other investigational agents

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients should have no greater than grade 2 neuropathy

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, irinotecan and capecitabine

• Patients with NYHA classification III or IV heart disease are ineligible

• Patients must not have a known hypersensitivity to 5-fluorouracil

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because the study drugs have the potential to cause teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued if the mother is treated with oxaliplatin, irinotecan or capecitabine

• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

• Patients who are unable to take oral medications are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Case Western Reserve University	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Joanna Brell, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00084617
• Other Study ID Numbers: NCI-2012-03010; CASE 1203; CDR0000365464; U01CA062502
• First Posted: Jun 11, 2004
• Last Update Posted: May 1, 2015
• Last Verified: Jul 1, 2013

• Additional relevant MeSH terms: Adenocarcinoma; Stomach Neoplasms; Capecitabine; Oxaliplatin; Irinotecan

Study Results

Participant Flow

Recruitment Details	This was a multi-center single treatment arm study involving four sites. Patients were recruited February 2004 through February 2007.

Arm/Group Title	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	39
COMPLETED	30
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57.8
Sex: Female, Male (Count of Participants)
Female	10 25.6%
Male	29 74.4%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Response Rates (RR) in Metastatic Gastric/GE Junction Tumors
Description	Response is defined as the number of patients with a CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of the target lesions or appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage or increase of target lesions.
Time Frame	at 12 weeks (after 2 cycles of treatment)

Outcome Measure Data

Analysis Population Description

Patients that completed at least 2 cycles of treatment

Arm/Group Title	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	30
Complete Response (CR)	2 5.1%
Partial Response (PR)	9 23.1%
Progressive Disease (PD)	3 7.7%
Stable Disease (SD)	16 41%

2. Secondary Outcome

Title	Complete Response (CR) and Partial Response (PR) Duration
Description	The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time Frame	at 40 months from study activation

Outcome Measure Data

Analysis Population Description

Patients that achieved either a CR or PR.

Arm/Group Title	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	11
Median (95% Confidence Interval) [months]	5.95

3. Secondary Outcome

Title	Overall Survival
Description	Length of time patients survived after treatment
Time Frame	at 40 months from study activation

Outcome Measure Data

Analysis Population Description

All patients enrolled in study

Arm/Group Title	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	39
Median (95% Confidence Interval) [months]	8.98

Adverse Events

Time Frame	Adverse events were assessed while patients were on study for up to 4 years
Arm/Group Title	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on days 1, 8, 15, and 22 and oral capecitabine twice daily on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
	Affected / at Risk (%)	# Events
Total	7/39 (17.9%)
Gastrointestinal disorders
Perforation, GI - Esophagus	1/39 (2.6%)
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/39 (2.6%)
Hemorrhage, GI - Esophagus	1/39 (2.6%)
General disorders
Death not associated with CTCAE term - Disease progression NOS	1/39 (2.6%)
Metabolism and nutrition disorders
Dehydration	1/39 (2.6%)
Nervous system disorders
Seizure	1/39 (2.6%)
Renal and urinary disorders
Renal failure	1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory	1/39 (2.6%)
Pleural effusion (non-malignant)	1/39 (2.6%)
Vascular disorders
Thrombosis/thrombus/embolism	1/39 (2.6%)
Hypotension	1/39 (2.6%)
Other (Not Including Serious) Adverse Events
	Treatment (Oxaliplatin, Irinotecan, Capecitabine)
	Affected / at Risk (%)	# Events
Total	35/39 (89.7%)
Blood and lymphatic system disorders
Albumin, serum-low (hypoalbuminemia)	24/39 (61.5%)
INR (International Normalized Ratio of prothrombin time)	2/39 (5.1%)
Leukocytes (total WBC)	18/39 (46.2%)
Lymphopenia	15/39 (38.5%)
Neutrophils/granulocytes (ANC/AGC)	14/39 (35.9%)
Platelets	14/39 (35.9%)
PTT (Partial Thromboplastin Time)	3/39 (7.7%)
Cardiac disorders
Palpitations	2/39 (5.1%)
Supraventricular and nodal arrhythmia	5/39 (12.8%)
Eye disorders
Vision-blurred vision	2/39 (5.1%)
Gastrointestinal disorders
Constipation	12/39 (30.8%)
Diarrhea	29/39 (74.4%)
Distension/bloating, abdominal	4/39 (10.3%)
Dysphagia (difficulty swallowing)	10/39 (25.6%)
Esophagitis	2/39 (5.1%)
Flatulence	5/39 (12.8%)
Heartburn/dyspepsia	4/39 (10.3%)
Mucositis/stomatitis	7/39 (17.9%)
Nausea	20/39 (51.3%)
Pain - Abdomen NOS	19/39 (48.7%)
Vomiting	12/39 (30.8%)
General disorders
Edema: limb	6/39 (15.4%)
Fatigue (asthenia, lethargy, malaise)	29/39 (74.4%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	3/39 (7.7%)
Pain - Pain NOS	4/39 (10.3%)
Rigors/chills	2/39 (5.1%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Neck NOS	4/39 (10.3%)
Infection with unknown ANC	4/39 (10.3%)
Investigations
Alkaline phosphatase	18/39 (46.2%)
ALT, SGPT (serum glutamic pyruvic transaminase)	4/39 (10.3%)
AST, SGOT(serum glutamic oxaloacetic transaminase)	6/39 (15.4%)
GGT (gamma-Glutamyl transpeptidase)	4/39 (10.3%)
Hemoglobin	25/39 (64.1%)
Weight gain	3/39 (7.7%)
Weight loss	19/39 (48.7%)
Metabolism and nutrition disorders
Anorexia	21/39 (53.8%)
Bicarbonate, serum-low	4/39 (10.3%)
Calcium, serum-high (hypercalcemia)	2/39 (5.1%)
Calcium, serum-low (hypocalcemia)	17/39 (43.6%)
Dehydration	12/39 (30.8%)
Glucose, serum-high (hyperglycemia)	21/39 (53.8%)
Glucose, serum-low (hypoglycemia)	5/39 (12.8%)
Magnesium, serum-high (hypermagnesemia)	2/39 (5.1%)
Magnesium, serum-low (hypomagnesemia)	7/39 (17.9%)
Phosphate, serum-low (hypophosphatemia)	3/39 (7.7%)
Potassium, serum-high (hyperkalemia)	6/39 (15.4%)
Potassium, serum-low (hypokalemia)	16/39 (41%)
Sodium, serum-high (hypernatremia)	3/39 (7.7%)
Sodium, serum-low (hyponatremia)	11/39 (28.2%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)	10/39 (25.6%)
Pain - Back	9/39 (23.1%)
Pain - Chest wall	5/39 (12.8%)
Pain - Chest/thorax NOS	3/39 (7.7%)
Pain - Extremity-limb	2/39 (5.1%)
Nervous system disorders
Dizziness	10/39 (25.6%)
Neuropathy: sensory	21/39 (53.8%)
Pain - Head/headache	3/39 (7.7%)
Taste alteration (dysgeusia)	4/39 (10.3%)
Psychiatric disorders
Insomnia	11/39 (28.2%)
Mood alteration - Agitation	2/39 (5.1%)
Mood alteration - Depression	4/39 (10.3%)
Renal and urinary disorders
Proteinuria	3/39 (7.7%)
Urinary frequency/urgency	3/39 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	8/39 (20.5%)
Dyspnea (shortness of breath)	9/39 (23.1%)
Hiccoughs (hiccups, singultus)	2/39 (5.1%)
Pneumonitis/pulmonary infiltrates	3/39 (7.7%)
Skin and subcutaneous tissue disorders
Dry skin	2/39 (5.1%)
Hair loss/alopecia (scalp or body)	4/39 (10.3%)
Rash/desquamation	2/39 (5.1%)
Rash: hand-foot skin reaction	2/39 (5.1%)
Vascular disorders
Flushing	3/39 (7.7%)
Hot flashes/flushes	6/39 (15.4%)
Hypertension	2/39 (5.1%)
Hypotension	3/39 (7.7%)
Sweating (diaphoresis)	3/39 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.