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

An Open-Labeled, Multicenter Phase II Study of Cabazitaxel in Refractory Metastatic Gastric or Gastroesophageal Adenocarcinoma

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

Study Overview

• Status: Completed
• Conditions: Gastric Adenocarcinoma; Gastroesophageal Adenocarcinoma; Distal Esophageal Adenocarcinoma
• Intervention / Treatment: Drug: Cabazitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (taxane naïve); No prior Taxane treatment. Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks	Drug: Cabazitaxel; 20mg IV over 1 hour every 3 weeks
Experimental: Arm B (prior taxane therapy); Subject previously treated with taxane. Cabazitaxel will be administered 20 mg/m2 IV over 1 hour every 3 weeks	Drug: Cabazitaxel; 20mg IV over 1 hour every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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
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	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
Percent of Participants Treated With Cabazitaxel With Event Free Survival	To examine other measures of efficacy such as overall survival in all evaluable patients	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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 20, 2012
• First Posted (Estimate): December 28, 2012

Study Record Updates

• Last Update Posted (Actual): April 3, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Gastric Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: 1208012946

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No