Esophageal, Gastric Cancer, Gastrooesophageal Cancer
Conditions
Keywords
esophageal cancer, gastroesophageal cancer, gastric cancer
Brief summary
The purpose of this study is to evaluate the effectiveness of Cabazitaxel, as well as safety and side effects for patients with advanced gastroesophageal cancer
Detailed description
Gastric cancer is the second most frequent cancer-related cause of death after lung cancer worldwide with approximately 900,000 cases per year. The incidence of gastric cancer is highest in East Asia, China and Japan. In the last two decades there has been a dramatic increase in North America and Europe of adenocarcinoma of the distal esophagus and GE junction which are indistinguishable from proximal gastric cancer. Cabazitaxel (XRP6258) is a semi-synthetic novel taxoid. Like traditional taxane drugs, it binds to and stabilizes tubilin structures resulting in inhibition of cold-induced microtubule depolymerization and cell division with subsequent inhibition of tumor cell proliferation. This novel agent, however, has poor affinity for P-glycoprotein--the protein product of multidrug resistance gene ABCB1. P-glycoprotein is a membrane-associated drug efflux pump and is thought to be a potential cause of taxane resistance in tumors. Also unlike traditional taxanes, Cabazitaxel has exhibited penetration through the blood-brain barrier (BBB.) Preclinical studies have demonstrated that Cabazitaxel was cytotoxic for cell lines with acquired resistance to doxorubicin, vincristine, vinblastine, paclitaxel or docetaxel. Taxanes have demonstrated statistically significant antitumor activity as both monotherapy and as part of combination triplet regimens in gastroesophageal carcinoma.Cabazitaxel has emerged as a novel investigational semi-synthetic taxoid that has established activity in cell lines refractory to traditional taxanes in preclinical studies and now in a phase III study in patients with metastatic prostate cancer. Cabazitaxel, with its low affinity for the P-glycoprotein drug efflux pump, may demonstrate superior response rates to docetaxel. Furthermore, as demonstrated in prostate cancer, cabazitaxel appears to have substantial activity in patients who have previously been treated with docetaxel. Phase I and II trials have been conducted demonstrating safety and efficacy of Cabazitaxel (XRP6258) in metastatic breast and prostate cancer. Neutropenia was the primary dose-limiting toxicity with the recommended dose established at 20 and 25mg/m2. The latter dose was used in the TROPIC trial, the pivotal phase III trial demonstrating improved overall survival and median progression free survival in patients with hormone resistant prostate cancer refractory to docetaxel who had received Cabazitaxel plus prednisone versus those who received mitaxantrone plus prednisone. Cabazitaxel given at IV doses of 25mg/m2 has demonstrated both safety and anti-tumor efficacy in phase I, II and now phase III trials The primary goal is to evaluate the activity of Cabazitaxel for the treatment of advanced gastroesophageal cancer that has progressed after at least one line of treatment for metastatic disease. Activity will be defined as a complete or partial response. The investigators will differentiate between a 10% level of activity and a 30% level of activity.
Interventions
DRUGjevtana
Cabazitaxel 25mg/m2, IV every 21 days until progression
Sponsors
Roger Williams Medical Center
Rhode Island Hospital
The Miriam Hospital
howard safran
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 are required to have histologically or pathologically confirmed metastatic gastric or esophageal adenocarcinoma. * Patients must demonstrate relapse or progression after at least one prior line of chemotherapy for metastatic disease. * Patients must have measurable disease by CT scan or MRI * Absolute neutrophil count ≥ 1,500/uL, platelet ≥ 100,000/uL and Hgb \> 8.0 g/dl. * Total bilirubin ≤ upper institutional limit of normal (ULN), and AST or ALT ≤ 3x ULN; if liver metastases then AST or ALT \< 5x ULN * Peripheral neuropathy must be ≤ Grade 1 * Creatinine \< 2 x ULN * ECOG performance status 0 to 2 * Minimum life expectancy of 12 weeks. * Age older than 18 years. * Voluntary, signed written informed consent. * Women of childbearing potential must have a negative pregnancy test Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
Exclusion criteria
* History of severe hypersensitivity reaction to Cabazitaxel or other drugs formulated with polysorbate 80. * Patients with known, untreated brain metastasis * Any uncontrolled severe, intercurrent illness. * Women who are breast-feeding. * Patients who have undergone major surgery, chemotherapy, or radiotherapy within the last 3 weeks. * Patients on concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Without Progression at 3 Months | every three cycles approx every 63 days | Response will be assessed via RECIST 1.1 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experienced a Toxicity Associated With Cabazitaxel for Patients With Metastatic Gastroesophageal Adenocarcinomas That Have Progressed After at Least One Line of Therapy for Metastatic Disease. | During treatment and through 30 days post treatment, approximately 7 months | CTCAE version 4. It is noted that the time frame was approximately 7 months, taking into account the total amount of treatment patients received on this trial. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Real Drug patients will receive Jevtana 25mg/m2, IV every 21 days until disease progression or unacceptable toxicity
jevtana: Cabazitaxel 25mg/m2, IV every 21 days until progression | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progression/worsening of Dx prior to txt | 2 |
Baseline characteristics
| Characteristic | Real Drug |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 67 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 5 / 13 |
Outcome results
Primary
Number of Patients Without Progression at 3 Months
Response will be assessed via RECIST 1.1 criteria
Time frame: every three cycles approx every 63 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Real Drug | Number of Patients Without Progression at 3 Months | 11 participants |
Secondary
Number of Patients Experienced a Toxicity Associated With Cabazitaxel for Patients With Metastatic Gastroesophageal Adenocarcinomas That Have Progressed After at Least One Line of Therapy for Metastatic Disease.
CTCAE version 4. It is noted that the time frame was approximately 7 months, taking into account the total amount of treatment patients received on this trial.
Time frame: During treatment and through 30 days post treatment, approximately 7 months
Population: Number of patients who experienced a toxicity on the trial. Not all toxicities may be related to study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Real Drug | Number of Patients Experienced a Toxicity Associated With Cabazitaxel for Patients With Metastatic Gastroesophageal Adenocarcinomas That Have Progressed After at Least One Line of Therapy for Metastatic Disease. | 13 Participants |