Clinical Trial: Cabozantinib-S-Malate in Treating Patients With Recurrent or Progressive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Trial of Cabozantinib (XL-184) (NSC #761968) in Women With Recurrent, Clear Cell Carcinoma of the Ovary, Fallopian Tube, or Peritoneum

Brief Summary: This phase II trial studies how well cabozantinib-s-malate works in treating patients with ovarian, fallopian tube, or primary peritoneal cavity cancer that has come back or is growing, spreading, or getting worse. Cabozantinib-s-malate may stop the growth of tumor cells by blocking the growth of new blood vessels necessary for tumor growth and also by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the anti-tumor activity of cabozantinib (XL184) (cabozantinib-s-malate) in women with persistent or recurrent clear cell ovarian cancer, based on the proportion of patients who survive progression-free for at least 6 months and the proportion who have objective tumor response (complete or partial).

SECONDARY OBJECTIVES:

I. To determine the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4 for cabozantinib (XL184).

II. To determine the progression free survival (PFS) and overall survival (OS) for patients with persistent or recurrent clear cell ovarian cancer treated with cabozantinib (XL184).

TERTIARY OBJECTIVES:

I. To examine the expression of phosphatase and tensin homolog gene (PTEN), phosphorylated v-akt murine thymoma viral oncogene homolog 1 (pAKT), cyclin E, and met proto-oncogene (MET) in formalin-fixed, paraffin-embedded tumor.

II. To examine MET amplification (fluorescence in situ hybridization) in tumor specimens and the relationship to response.

OUTLINE:

Patients receive cabozantinib-s-malate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Complete or partial objective tumor response, evaluated using the RECIST v1.1 [ Time Frame: Up to 28 days ]
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months ]
    A modification of the bivariate two-stage design of Sill, et al, which uses the numbers of patients progression-free at 6 months and the number with objective responses to make inferences about the efficacy of the study drug will be used. Will be characterized graphically and using descriptive statistics such as median survival based on Kaplan-Meier estimates.


Original Primary Outcome:

  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months ]
    A modification of the bivariate two-stage design of Sill, et al, which uses the numbers of patients progression-free at 6 months and the number with objective responses to make inferences about the efficacy of the study drug will be used. Will be characterized graphically and using descriptive statistics such as median survival based on Kaplan-Meier estimates.
  • Complete or partial objective tumor response, evaluated using the RECIST v1.1 [ Time Frame: Up to 28 days ]


Current Secondary Outcome:

  • Incidence of toxicity as assessed by CTCAE v4 [ Time Frame: Up to 5 years ]
    The nature, frequency and maximum degree of toxicity will be determined. Events will be tabulated using maximum grade for each adverse event term regardless of attribution to study drug.
  • Overall survival [ Time Frame: Time from start of treatment to time of death or the date of last contact, assessed up to 5 years ]
    Will be characterized graphically and using descriptive statistics such as median survival based on Kaplan-Meier estimates.
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ]
    Will be characterized graphically and using descriptive statistics such as median survival based on Kaplan-Meier estimates.


Original Secondary Outcome:

  • Incidence of toxicity as assessed by CTCAE v4 [ Time Frame: Up to 5 years ]
    The nature, frequency and maximum degree of toxicity will be determined. Events will be tabulated using maximum grade for each adverse event term regardless of attribution to study drug.
  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ]
    Will be characterized graphically and using descriptive statistics such as median survival based on Kaplan-Meier estimates.
  • Overall survival [ Time Frame: Time from start of treatment to time of death or the date of last contact, assessed up to 5 years ]
    Will be characterized graphically and using descriptive statistics such as median survival based on Kaplan-Meier estimates.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 9, 2014
Date Started: April 2015
Date Completion:
Last Updated: May 26, 2017
Last Verified: May 2017