Esophageal Neoplasms, Gastric Cancer
Conditions
Keywords
Gastroesophageal cancer, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
Brief summary
This study is for people with advanced gastric or gastroesophageal cancer. This study is being done to find out how long it takes tumors to grow after receiving treatment with the drugs irinotecan (also known as CPT-11) and docetaxel (also known as Taxotere). Irinotecan is a drug that has been approved by the Food and Drug Administration (FDA). Irinotecan has been approved for treatment of cancer of the colon and rectum. Docetaxel is another drug approved by the FDA. Docetaxel is approved for treatment of breast, prostate and lung cancer. However, the FDA has authorized the use of irinotecan and docetaxel in this study. This study will evaluate the effects of these drugs on participant's tumors. The side effects of the combination of irinotecan and docetaxel will also be evaluated. This study will also measure the levels of certain substances in participant's tumors. These substances, called genes (which are the cell's blueprint), affect how people's bodies react to the cancer drugs. Genes will also be measured in participant's blood. The researchers want to see if these substances can predict response to the study drugs.
Interventions
DRUGirinotecan, docetaxel
docetaxel 30 mg/m2 IV infusion days 1 and 8, with irinotecan 65 mg/m2 IV infusion on days 1 and 8.
Sponsors
Sanofi
University of Southern California
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have clinically documented unresectable or metastatic gastric cancer or gastroesophageal adenocarcinoma and histologic confirmation of the diagnosis with tumor. * Patients must have received one prior chemotherapeutic regimen for metastatic or unresectable disease. Patients may not have received prior therapy with irinotecan or a taxane. * Tissue from tumor must be available. This may be paraffin embedded tissue from previous biopsy/resection or if it is not available, a repeat biopsy must be performed. * Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy. * Patients must have measurable disease by clinical exam or radiologic studies, that is at least one lesion measurable in at least one dimension, measuring 10 mm or more on a spiral CT scan, or at least 20 mm by an exam or a non-spiral scan. If prior radiation therapy was administered, measurable disease must be outside the radiation field. * Patients must have a Zubrod performance status of 0-2. * Patients must have a predicted life expectancy of at least 12 weeks. * Patients must have: * a pre-treatment granulocyte count (i.e., segmented neutrophils + bands) of \>1,500/mm3, * a hemoglobin level of greater than or equal to 9.0 gm/dl, and * a platelet count of \>100,000/mm3. * Patients must have adequate renal function as documented by a calculated creatinine clearance \> 60. * Patients must have adequate hepatic function as documented by a serum bilirubin less than or equal to the institutional upper limit of normal, regardless of whether patients have liver involvement secondary to tumor. * No major surgery within 1 month of starting study drug. * Women of childbearing potential must have a negative pregnancy test. * Peripheral neuropathy: must be \< grade 1
Exclusion criteria
* Patients may not have a history of an allergy to irinotecan. * Patients with any active or uncontrolled infection, including known HIV infection. * Patients with psychiatric disorders that would interfere with consent or follow-up. * Patients with a history of myocardial infarction within the previous six months or congestive heart failure requiring therapy. * Pregnant or lactating women. Men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on treatment and for at least 3 months thereafter. * Presence of clinically apparent central nervous system metastases or carcinomatous meningitis. * Patients with a history of seizures are ineligible. Patients receiving phenytoin, phenobarbital, or other anti-epileptic prophylaxis are ineligible. * Patients with any other severe concurrent disease, which in the judgment of the investigator would make the patient inappropriate for entry into this study. * Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (Complete, Partial, Stable and Progression) | every 2 cycles | Objective response was defined using standard RECIST criteria. CR (complete response) = disappearance of all target lesions; PR (partial response) = 30% decrease in the sum of the longest diameter or target lesions; PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions SD (stable disease) = small changes that do not meet criteria of CR, PR, and PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | every 2 cycles | Progression free survival is measured from the start of treatment until the time the participant is first recorded as having disease progression, or death due to any cause. If a participant has not progressed or died, progression free survival is censored at the time of the last follow up. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the University of Southern California cancer center facilities between April 14, 2005 and January 11, 2012.
Pre-assignment details
There are no pre-assignment requirements for this study.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 - Irinotecan and Docetaxel Irinotecan given day 1 and 8 every 21 days Docetaxel given day 1 and 8 every 21 days
irinotecan, docetaxel: docetaxel 30 mg/m2 IV infusion days 1 and 8, with irinotecan 65 mg/m2 IV infusion on days 1 and 8. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Death | 3 |
| Overall Study | Drug delayed more than 28 days | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Arm 1 - Irinotecan and Docetaxel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 40 |
| other Total, other adverse events | 38 / 40 |
| serious Total, serious adverse events | 29 / 40 |
Outcome results
Primary
Objective Response (Complete, Partial, Stable and Progression)
Objective response was defined using standard RECIST criteria. CR (complete response) = disappearance of all target lesions; PR (partial response) = 30% decrease in the sum of the longest diameter or target lesions; PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions SD (stable disease) = small changes that do not meet criteria of CR, PR, and PD.
Time frame: every 2 cycles
Population: Population analyzed included all participants who received at least 6 weeks of treatment (or who were discontinued due to progressive disease or for reason of toxicity within the first 6 weeks of study). Two subjects had no tumor evaluation and follow up data available. Analysis was per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - Irinotecan and Docetaxel | Objective Response (Complete, Partial, Stable and Progression) | PR | 7 participants |
| Arm 1 - Irinotecan and Docetaxel | Objective Response (Complete, Partial, Stable and Progression) | CR | 0 participants |
| Arm 1 - Irinotecan and Docetaxel | Objective Response (Complete, Partial, Stable and Progression) | SD | 22 participants |
| Arm 1 - Irinotecan and Docetaxel | Objective Response (Complete, Partial, Stable and Progression) | PD | 9 participants |
Secondary
Progression Free Survival
Progression free survival is measured from the start of treatment until the time the participant is first recorded as having disease progression, or death due to any cause. If a participant has not progressed or died, progression free survival is censored at the time of the last follow up.
Time frame: every 2 cycles
Population: Population analyzed included all participants who received at least 6 weeks of treatment (or who were discontinued due to progressive disease or for reason of toxicity within the first 6 weeks of study). Two subjects had no tumor evaluation and follow up data available. Analysis was per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 - Irinotecan and Docetaxel | Progression Free Survival | 4.1 Months |