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A Phase II Study Of Cabazitaxel For Metastatic Gastroesophageal Adenocarcinomas That Have Relapsed After At Least One Line Of Chemotherapy

Phase 2
18 Years
Not Enrolling
Esophageal, Gastrooesophageal Cancer, Gastric Cancer

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Trial Information

A Phase II Study Of Cabazitaxel For Metastatic Gastroesophageal Adenocarcinomas That Have Relapsed After At Least One Line Of Chemotherapy

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

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the response rate of Cabazitaxel in patients with metastatic gastroesophageal adenocarcinoma that have progressed after at least one line of therapy for metastatic disease

Outcome Time Frame:

every three cycles approx every 63 days

Safety Issue:


Principal Investigator

Howard safran, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brown University


United States: Institutional Review Board

Study ID:

BrUOG 243



Start Date:

June 2011

Completion Date:

March 2013

Related Keywords:

  • Esophageal
  • Gastrooesophageal Cancer
  • Gastric Cancer
  • esophageal cancer
  • gastroesophageal cancer
  • gastric cancer
  • Esophageal Diseases
  • Stomach Neoplasms



Brown University Oncology Group Providence, Rhode Island  02912
Memorial Hospital Pawtucket, Rhode Island  02860
Roger Williams Providence, Rhode Island  02906