Phase II Study of Cabazitaxel in Refractory Metastatic Gastric or Gastroesophageal Adenocarcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Weill Medical College of Cornell University
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01757171
First received: December 6, 2012
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

Cabazitaxel will be administered 25 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


Condition Intervention Phase
Gastric Adenocarcinoma
Gastroesophageal Adenocarcinoma
Distal Esophageal Adenocarcinoma
Drug: Cabazitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Labeled, Multicenter Phase II Study of Cabazitaxel in Refractory Metastatic Gastric or Gastroesophageal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Response to cabazitaxel [ Time Frame: estimation of 4 years to determine response on all subjects ] [ Designated as safety issue: No ]
    To demonstrate the antitumor activity as assessed by the rate of progression free survival at three months of the sanofi-aventis product cabazitaxel 25mg/m2 IV over 1 hour every 3 weeks in subjects with previously treated metastatic gastroesophageal adenocarcinoma who are either taxane naïve, or taxane previously treated.


Secondary Outcome Measures:
  • Event free survival of subjects treated with cabazitaxel [ Time Frame: Approximately 4 years to assess response on all subjects accrued to the study ] [ Designated as safety issue: No ]
    To examine other measures of efficacy including overall progression free and overall survival in all evaluable patients, and the objective response rate in patients with measurable disease.

  • Toxicity profile of cabazitaxel. [ Time Frame: Approximated 4 years to obtain safety data for all subjects. ] [ Designated as safety issue: Yes ]
    The frequency of subjects experiencing toxicities will be tabulated. Toxicities will be assessed and graded according to CTCAE v. 4.0. Exact 95% confidence intervals around the toxicity proportions will be calculated to assess the precision of the obtained estimate

  • Response to cabazitaxel across gastric cancer subtypes. [ Time Frame: Approximately 4 years to obtain efficacy data on all subjects. ] [ Designated as safety issue: No ]
    Response will be measured by the disappearance of the sum of the diameters of all target lesions observed on CT/MRI scan.


Estimated Enrollment: 86
Study Start Date: December 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (taxane naïve)
No prior Taxane treatment. Cabazitaxel will be administered 25 mg/m2 IV over 1 hour every 3 weeks
Drug: Cabazitaxel
25mg IV over 1 hour every 3 weeks
Experimental: Arm B (prior taxane therapy)
Subject previously treated with taxane. Cabazitaxel will be administered 25 mg/m2 IV over 1 hour every 3 weeks
Drug: Cabazitaxel
25mg IV over 1 hour every 3 weeks

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 25 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.

  Eligibility

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

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.
  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: NCT01757171

Contacts
Contact: Alice Mercado, RN 212-746-5430 alm2051@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Manish Shah, MD    646-962-6200      
Sponsors and Collaborators
Weill Medical College of Cornell University
Sanofi
Investigators
Principal Investigator: Manish Shah, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01757171     History of Changes
Other Study ID Numbers: 1208012946
Study First Received: December 6, 2012
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
Gastric Cancer

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 22, 2014