Clinical Trial: Study of the Efficacy and Safety of Pasireotide s.c. +/- Cabergoline in Patients With Cushing's Disease

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

Official Title: A Phase II Trial to Assess the Efficacy and Safety of Pasireotide s.c. Alone or in Combination With Cabergoline in Patients With Cushing's Disease

Brief Summary: This study is to assess whether pasireotide alone and combined with cabergoline will give reliefs on patients with recurrent, persistent and newly diagnosed Cushing's disease. The study will also assess study drug safety, the changes in Quality of Life and on clinical signs and symptoms of Cushing's disease.

Detailed Summary: This study is to assess whether pasireotide alone and combined with cabergoline will give reliefs on patients with recurrent, persistent and newly diagnosed Cushing's disease. The study will also assess study drug safety, the changes in Quality of Life and on clinical signs and symptoms of Cushing's disease. The study consists pasireotide-untreated patients at screening and patients currently treated with maximal tolerated doses of pasireotide. Core phase will consist of pasireotide-untreated patients at screening - this includes patients who have never received pasireotide or patients who have received pasireotide sometime in the past but it was not discontinued because of safety. These patients will start pasireotide at 0.6mg twice a day for 8 weeks. Should biochemical control not be achieved the dose will be increased to 0.9mg twice a day. If biochemical control is still not achieved, cabergoline at increasing dose will be added. Patients currently treated with maximal tolerated doses of pasireotide monotherapy for at least 8 weeks at 0.3mg twice a day, 0.6mg twice a day or 0.9mg twice a day, but still did not achieve biochemical control will add cabergoline at increasing dose. After 35 weeks of treatment at core phase, patients will have the option to continue study treatment in extension phase if pasireotide is not yet approved for commercial use and/or reimbursed - if country reimbursement is applicable.
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Proportion of patients who attain mUFC ≤1.0 ULN at week 35 with pasireotide alone or in combination with cabergoline [ Time Frame: at week 35 ]

Proportion of patients who attain mUFC ≤ 1.0 x ULN at week 35 with pasireotide alone or in combination with cabergoline


Original Primary Outcome:

  • mUFC [ Time Frame: at week 35 ]
    Proportion of patients who attain mUFC ≤ 1.0 x ULN at week 35 with pasireotide alone or in combination with cabergoline in Group 1
  • mUFC [ Time Frame: at week 17 ]
    Proportion of patients who attain a mUFC ≤ 1.0 x ULN at week 17 with pasireotide with combination of cabergoline in Group 2


Current Secondary Outcome:

  • Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured [ Time Frame: at weeks 4, 8, 13, 17, 22, 26, 31, 35 ]
    Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured
  • Proportion of patients attain mUFC ≤ 1.0 x ULN as assessed at each scheduled visit when UFC is measured [ Time Frame: at weeks 4, 8, 13, 17, 22, 26, 31 ]
    Proportion of patients that attain mUFC ≤ 1.0 x ULN as assessed at each scheduled visit when UFC is measured
  • Proportion of patients who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured [ Time Frame: at weeks 4, 8, 13, 17, 22, 26, 31, 35 ]
    Proportion of patients who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured
  • Duration of controlled or partially controlled response [ Time Frame: from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN ]
    Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC ≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN and the reduction from baseline falls to less than 50% from the first time
  • Change from baseline in plasma ACTH and serum cortisol over time [ Time Frame: at 4, 8, 13, 17, 22, 26, 31 and 35 ]
    Change from baseline in plasma ACTH and serum cortisol over time
  • Toxicity will be assessed using NCI-CTCAE v.4 and for laboratory assessments [ Time Frame: at baseline visits, and at weeks 4, 8, 13, 17, 22, 26, 31, 35 and study completion visit ]
    Shift tables using CTC grades to compare baseline to the worst post-baseline value


Original Secondary Outcome:

  • Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured [ Time Frame: at weeks 0, 4, 8, 13, 17, 22, 26, 31, 35 for group 1 ]
    Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured for Group 1 patients
  • Proportion of patients attain mUFC ≤ 1.0 x ULN as assessed at each scheduled visit when UFC is measured [ Time Frame: at weeks 0, 4, 8, 13, 17, 22, 26, 31, 35 for group 1 ]
    Proportion of patients that attain mUFC ≤ 1.0 x ULN as assessed at each scheduled visit when UFC is measured for Group 1 patients
  • Proportion of patients who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured [ Time Frame: at weeks 0, 4, 8, 13, 17, 22, 26, 31, 35 for group 1 ]
    Proportion of patients who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured for Group 1 patients
  • Duration of controlled or partially controlled response [ Time Frame: from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN ]
    Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC ≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN and the reduction from baseline falls to less than 50% from the first time for Group 1 and Group 2 patients, separately
  • Change from baseline in plasma ACTH and serum cortisol over time [ Time Frame: at baseline visit and weeks 0, 4, 8, 13, 17, 22, 26, 31 and 35 for group 1 ]
    Change from baseline in plasma ACTH and serum cortisol over time for Group 1 patients
  • Ctrough at baseline [ Time Frame: at baseline ]
    Ctrough at baseline for Group 2 patients only
  • Ctrough at week 8 [ Time Frame: at week 8 ]
    Ctrough at week 8 for Group 2 patients only
  • Ctrough [ Time Frame: at week 17 ]
    Ctrough at week 17 for Group 2 patients only
  • Cmax at baseline [ Time Frame: at baseline ]
    Cmax at baseline for Group 2 patients only
  • Cmax at week 8 [ Time Frame: at week 8 ]
    Cmax at week 8 for Group 2 patients only
  • Cmax [ Time Frame: at week 17 ]
    Cmax at week 17 for Group 2 patients only
  • Toxicity will be assessed using NCI-CTCAE v.4 and for laboratory assessments [ Time Frame: at screening, baseline visits, and at weeks 4, 8, 13, 17, 22, 26, 31, 35 and study completion visit ]
    Toxicity will be assessed using NCI-CTCAE v.4 and for laboratory assessments that include biochemistry, hematology, urinalysis; special safety assessments that include the regular monitoring and recording of blood glucose insulin, HbA1c, GH and IGF-1, thyroid and liver function tests, gallbaldder examinizations and ECGs. Concomitant medications/signficant non-drug therapies will be assessed too for group 1 patients
  • Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured [ Time Frame: at weeks 0, 4, 8, 13, 17 for group 2 ]
    Percentage change in mUFC from baseline to study end at each scheduled visit when UFC is measured for Group 1 patients
  • Proportion of patients attain mUFC ≤ 1.0 x ULN as assessed at each scheduled visit when UFC is measured [ Time Frame: at weeks 0, 4, 8, 13, 17 for group 2 ]
    Proportion of patients attain mUFC ≤ 1.0 x ULN as assessed at each scheduled visit when UFC is measured for group 2 patients
  • Proportion of patients who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured [ Time Frame: at weeks 0, 4, 8, 13, 17 for group 2 ]
    Proportion of patients who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC as assessed at each scheduled visit when UFC is measured for group 2 patients
  • Change from baseline in plasma ACTH and serum cortisol over time [ Time Frame: at baseline visit and weeks 0, 4, 8, 13, 17 ]
    Change from baseline in plasma ACTH and serum cortisol over time for group 2 patients
  • Toxicity will be assessed using NCI-CTCAE v.4 and for laboratory

    Information By: Novartis

    Dates:
    Date Received: June 10, 2013
    Date Started: March 6, 2014
    Date Completion: December 31, 2017
    Last Updated: March 6, 2017
    Last Verified: March 2017