Clinical Trial: Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer

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

Official Title: A PHASE II EVALUATION OF DALANTERCEPT, A NOVEL SOLUBLE RECOMBINANT ACTIVIN RECEPTOR-LIKE KINASE 1 (ALK-1) INHIBITOR RECEPTOR-FUSION PROTEIN, IN THE TREATMENT OF RECURRENT OR PERSISTENT ENDOMETRIAL CAR

Brief Summary: This phase II trial studies how well dalantercept works in treating patients with recurrent or persistent endometrial cancer. Dalantercept may stop the growth of endometrial cancer by blocking blood flow to the tumor.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with persistent or recurrent endometrial cancer who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial) when treated with dalantercept.

II. To determine the nature and degree of toxicity of dalantercept in this cohort of patients.

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent endometrial cancer treated with dalantercept.

TERTIARY OBJECTIVES:

I. To measure the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), activin receptor-like kinase 1 (ALK1), endoglin (CD105), and other markers via immunohistochemistry (IHC) and determine if there is correlation between expression and clinical response to treatment.

II. To determine the correlation between ALK1 gene expression, other markers, and clinical response to treatment.

III. To determine the correlation between concentration of VEGF, bone morphogenetic protein 9 (BMP9), bone morphogenetic protein 10 (BMP10), and ALK1 in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay (ELISA), and clinical response to treatment.

IV. To correlate somatic mutations in candidate genes with response to therapy.

OUTLINE: This is a multicenter
Sponsor: Gynecologic Oncology Group

Current Primary Outcome:

  • Response [ Time Frame: Scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease. Responses must be confirmed. ]
    Response was defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and based on imaging done every other cycle. Responses can be either partial or complete. Per RECIST v1.1 target and non-target lesions are assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target and non-target lesions and all lymph nodes must be < 10 mm in short axis; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD.
  • Treatment and Progression-free Survival at 6 Months [ Time Frame: CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease ]

    Treatment and Progression-free Survival is defined as the duration alive from study entry until progression is documented, death or non-protocol treatment is initiated; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

    Non-protocol treatment initiation prior to disease pro

    Original Primary Outcome:

    • PFS until subsequent therapy for at least 6 months as measured by RECIST
    • Objective tumor response (complete or partial response) as measured by RECIST, assessed up to 5 years


    Current Secondary Outcome:

    • Progression-free Survival at 6 Months [ Time Frame: : CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease. ]

      Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

      Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for progression-free survival at 6 months.

    • Duration of Progression-free Survival [ Time Frame: CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease. ]
      Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.
    • Duration of Survival [ Time Frame: Patients are followed every three months for the first two years and then every six months for the next three years. ]
      Duration of survival is defined as the duration alive from study entry until death or last contact.
    • Adverse Events (Primary Serious and All Other AEs) [ Time Frame: Every cycle of study treatment and after treatment for a maximum of 5 years from study entry ]
      The frequencies of the maximum grade of any serious adverse event or all other adverse events by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported.


    Original Secondary Outcome:

    • PFS characterized graphically and using descriptive statistics such as median survival, assessed up to 5 years
    • OS characterized graphically and using descriptive statistics such as median survival, assessed up to 5 years
    • Adverse events, as assessed by CTCAE, for up to 21 days


    Information By: Gynecologic Oncology Group

    Dates:
    Date Received: July 15, 2012
    Date Started: September 2012
    Date Completion:
    Last Updated: January 7, 2016
    Last Verified: January 2016