Distal Esophageal Adenocarcinoma, Gastric Adenocarcinoma, Gastroesophageal Adenocarcinoma
Conditions
Keywords
Gastric Cancer
Brief summary
Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks, as is the standard administration dose and schedule. This application is a non-labeled indication for cabazitaxel and will inform future drug development in gastroesophageal malignancies, where docetaxel remains an approved first line agent, but is not routinely used due to excessive toxicity and marginal efficacy. At the conclusion of this study, we hope to demonstrate activity of single agent cabazitaxel in refractory gastric cancer, with preferential activity in one or more gastric cancer subtypes
Detailed description
Prior to initiating protocol therapy, patients will undergo screening evaluations, to be done within 30 days of protocol initiation unless otherwise noted. Patients who are taxane naïve will be assigned to arm A and patients who have had prior taxane therapy will be assigned to Arm B. Each arm will be analyzed separately for the primary study endpoint of 3 month progression free survival rate (PFS), as defined as the time from the start of treatment to the date of disease progression or death. Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks. In the absence of treatment delays due to adverse event(s), treatment may continue until disease progression; intercurrent illness that prevents further administration of treatment; unacceptable adverse event(s); patient decides to withdraw; general or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator. Patients will be followed for 6 months after removal from study or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
Interventions
DRUGCabazitaxel
20mg IV over 1 hour every 3 weeks
Sponsors
Sanofi
Weill Medical College of Cornell University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must have histologically or cytologically confirmed gastric, or gastroesophageal adenocarcinoma, or distal esophageal adenocarcinoma. 2. Subject must have unresectable or metastatic gastroesophageal adenocarcinoma. 3. Subject must have evaluable disease as per RECIST criteria. 4. Subject must have had at least one prior cytotoxic chemotherapy regimen for unresectable or metastatic disease. Prior taxane therapy is allowed. 5. Age \>/=18 years old. 6. ECOG performance status status \>/= 2 7. Subject must have normal organ and marrow function as defined below: * WBC \>/= 3,000/uL * Total Bilirubin ≤ 1.5 x upper limits of normal * AST (SGOT) ≤ 2.5 x upper limits of normal * ALT (SGPT) ≤ 2.5 x upper limits of normal * Hgb \> 7.5 g/dl (without transfusion within 7 days) * ANC \> 1000 /ml * Plt \> 75 K/ml (without transfusion) * Creatinine\* \< 2.0 g/dl \*or a calculated creatinine clearance \> 45/cc (using Cockroft-Gault formula) 9\. 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. 10. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. Subject with previously untreated unresectable or metastatic gastroesophageal adenocarcinoma. 2. Subject with more than 2 prior cytotoxic therapies (not including treatment administered for locally curable disease) for unresectable or metastatic gastroesophageal adenocarcinoma. 3. Subject with CNS metastases with active neurologic dysfunction. These patients are excluded because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse event. 4. Significant medical co-morbidity that would preclude safe administration of cytotoxic therapy, including but not limited to: a.Cardiac disease i. Unstable angina ii. Myocardial infarction \< 3 months prior to study initiation b. Ongoing serious infection i. Bacteremia or sepsis requiring intravenous antibiotics ii. HIV with AIDS defining illness c.Inadequate oral nutritional intake i. Requirement for daily intravenous fluids or total parenteral nutrition. d. Psychiatric illness/social situations that would limit compliance with study requirement 5. Subject who has had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from prior treatment related toxicity with persistent symptoms \>/= grade 2 due to agents administered more than 4 weeks earlier. 6. Subject may not receive another investigational agent. 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Cabazitaxel, or to drugs formulated with polysorbate 80. 8. Pregnant (positive pregnancy test) and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression at the 3 Month Follow up Visit | 3 months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Results below list the number of participants who progressed at the 3 month follow up visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Event Free Survival of Subjects Treated With Cabazitaxel | From date of first subject treated until the date of last subject documented progression or date of death from any cause, whichever came first, assessed up to 6 months | To examine other measures of efficacy such as overall progression free in all evaluable patients |
| Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | From date of first subject treated until the date of last subject documented progression or date of death from any cause, whichever came first, assessed up to 6 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
| Percent of Participants Treated With Cabazitaxel With Event Free Survival | From date of first subject treated until the date of last subject documented progression or date of death from any cause, whichever came first, assessed up to 6 months | To examine other measures of efficacy such as overall survival in all evaluable patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (Taxane naïve) No prior Taxane treatment. Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks
Cabazitaxel: 20mg IV over 1 hour every 3 weeks | 53 |
| Arm B (Prior Taxane Therapy) Subject previously treated with taxane. Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks
Cabazitaxel: 20mg IV over 1 hour every 3 weeks | 23 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 1 |
| Overall Study | Disease Progression | 1 | 0 |
| Overall Study | ECOG decline | 1 | 0 |
| Overall Study | Hospitalization | 1 | 0 |
Baseline characteristics
| Characteristic | Arm A (Taxane naïve) | Total | Arm B (Prior Taxane Therapy) |
|---|---|---|---|
| Age, Continuous | 62.1 years | 61.67 years | 57.34 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 50 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 17 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 17 Participants | 8 Participants |
| Race (NIH/OMB) White | 36 Participants | 50 Participants | 14 Participants |
| Region of Enrollment United States | 53 Participants | 76 Participants | 23 Participants |
| Sex: Female, Male Female | 20 Participants | 26 Participants | 6 Participants |
| Sex: Female, Male Male | 33 Participants | 50 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 53 | 27 / 27 |
| serious Total, serious adverse events | 27 / 53 | 15 / 23 |
Outcome results
Primary
Number of Participants With Progression at the 3 Month Follow up Visit
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Results below list the number of participants who progressed at the 3 month follow up visit
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Taxane naïve) | Number of Participants With Progression at the 3 Month Follow up Visit | 15 participants |
| Arm B (Prior Taxane Therapy) | Number of Participants With Progression at the 3 Month Follow up Visit | 7 participants |
Secondary
Duration of Event Free Survival of Subjects Treated With Cabazitaxel
To examine other measures of efficacy such as overall progression free in all evaluable patients
Time frame: From date of first subject treated until the date of last subject documented progression or date of death from any cause, whichever came first, assessed up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (Taxane naïve) | Duration of Event Free Survival of Subjects Treated With Cabazitaxel | 2.17 months |
| Arm B (Prior Taxane Therapy) | Duration of Event Free Survival of Subjects Treated With Cabazitaxel | 1.31 months |
Secondary
Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: From date of first subject treated until the date of last subject documented progression or date of death from any cause, whichever came first, assessed up to 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (Taxane naïve) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Partial Response | 5 participants |
| Arm A (Taxane naïve) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Progression Disease | 34 participants |
| Arm A (Taxane naïve) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Complete Response | 1 participants |
| Arm A (Taxane naïve) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Death | 1 participants |
| Arm A (Taxane naïve) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Stable Disease | 12 participants |
| Arm B (Prior Taxane Therapy) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Death | 0 participants |
| Arm B (Prior Taxane Therapy) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Stable Disease | 5 participants |
| Arm B (Prior Taxane Therapy) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Partial Response | 3 participants |
| Arm B (Prior Taxane Therapy) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Complete Response | 0 participants |
| Arm B (Prior Taxane Therapy) | Number of Participants With Response to Cabazitaxel Across Gastric Cancer Subtypes | Progression Disease | 14 participants |
Secondary
Percent of Participants Treated With Cabazitaxel With Event Free Survival
To examine other measures of efficacy such as overall survival in all evaluable patients
Time frame: From date of first subject treated until the date of last subject documented progression or date of death from any cause, whichever came first, assessed up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Taxane naïve) | Percent of Participants Treated With Cabazitaxel With Event Free Survival | 11.32 percentage of participants |
| Arm B (Prior Taxane Therapy) | Percent of Participants Treated With Cabazitaxel With Event Free Survival | 13 percentage of participants |