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Chemotherapy for Patients With Gastroesophageal Cancers Who Have Progressed After One Prior Chemo Regimen

This study has been terminated.
(As of 12/12/12 study closed to enrollment because study was determined to be ineffective.)
Sponsor:
Collaborators:
Roger Williams Medical Center
Rhode Island Hospital
The Miriam Hospital
Information provided by (Responsible Party):
howard safran, Brown University
ClinicalTrials.gov Identifier:
NCT01365130
First received: May 11, 2011
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Esophageal
Gastrooesophageal Cancer
Gastric Cancer
Drug: jevtana
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Cabazitaxel For Metastatic Gastroesophageal Adenocarcinomas That Have Relapsed After At Least One Line Of Chemotherapy

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Number of Patients Without Progression at 3 Months [ Time Frame: every three cycles approx every 63 days ] [ Designated as safety issue: Yes ]
    Response will be assessed via RECIST 1.1 criteria


Secondary Outcome Measures:
  • To Assess the Toxicity Associated With Cabazitaxel for Patients With Metastatic Gastroesophageal Adenocarcinomas That Have Progressed After at Least One Line of Therapy for Metastatic Disease. [ Time Frame: at approx 6, 12 and 18 months ] [ Designated as safety issue: Yes ]
    We will look at the number of patients who have Hematologic Toxicity as well as non-hematologic toxicity


Enrollment: 15
Study Start Date: June 2011
Study Completion Date: August 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: real drug
patients will receive Jevtana 25mg/m2, IV every 21 days until disease progression or unacceptable toxicity
Drug: jevtana
Cabazitaxel 25mg/m2, IV every 21 days until progression
Other Name: Cabazitaxel

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01365130

Locations
United States, Rhode Island
Memorial Hospital
Pawtucket, Rhode Island, United States
Brown University Oncology Research Group
Providence, Rhode Island, United States, 02903
Roger Williams
Providence, Rhode Island, United States, 02906
Sponsors and Collaborators
howard safran
Roger Williams Medical Center
Rhode Island Hospital
The Miriam Hospital
Investigators
Principal Investigator: Howard safran, MD Brown University
  More Information

Additional Information:
No publications provided

Responsible Party: howard safran, Priniciple Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01365130     History of Changes
Other Study ID Numbers: BrUOG 243
Study First Received: May 11, 2011
Results First Received: February 20, 2014
Last Updated: June 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Brown University:
esophageal cancer
gastroesophageal cancer
gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Site
Stomach Diseases

ClinicalTrials.gov processed this record on November 20, 2014