Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib

• ClinicalTrials.gov Identifier: NCT00756509
• Recruitment Status: Active, not recruiting
• First Posted: September 22, 2008
• Last Update Posted: March 20, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: September 19, 2008
• First Posted Date: September 22, 2008
• Last Update Posted Date: March 20, 2024
• Actual Study Start Date: August 29, 2008
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 16, 2009): To evaluate the efficacy of Nilotinib in patients with unresectable or metastatic gastrointestinal stromal tumors. Efficacy is defined as the proportion of patients showing stable disease (SD), partial response (PR) or complete response (CR) during the [ Time Frame: 6 months ]
• Original Primary Outcome Measures (submitted: September 19, 2008): To evaluate the efficacy of Nilotinib in patients with unresectable or metastatic gastrointestinal stromal tumors. Efficacy is defined as the proportion of patients showing stable disease (SD), partial response (PR) or complete response (CR) during the

Current Secondary Outcome Measures (submitted: October 16, 2009)

• objective tumor response rate based on RECIST criteria (complete response (CR) and partial response PR) [ Time Frame: 6 months ]
• time to overall response (PR or CR) [ Time Frame: 6 months ]
• duration of response [ Time Frame: 6 months ]
• progression free survival (PFS) during the first 6 months using RECIST criteria [ Time Frame: 6 months ]
• overall survival (OS) [ Time Frame: 6 months ]
• safety and tolerability [ Time Frame: 6 months ]
• population pharmacokinetics of Nilotinib [ Time Frame: 6 months ]

Original Secondary Outcome Measures (submitted: September 19, 2008)

• objective tumor response rate based on RECIST criteria (complete response (CR) and partial response PR)
• time to overall response (PR or CR)
• duration of response
• progression free survival (PFS) during the first 6 months using RECIST criteria
• overall survival (OS)
• safety and tolerability
• population pharmacokinetics of Nilotinib

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
• Official Title: An Open-label, Multi-center, Single-arm Study to Evaluate the Efficacy of Nilotinib in Adult Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line Treatment
• Brief Summary: The purpose of this multicenter, single-arm, exact binomial single-stage, phase II trial is to evaluate the efficacy of Nilotinib in patients with unresectable or metastatic gastrointestinal stromal tumors
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastrointestinal Stromal Tumors

Intervention

Drug: Nilotinib

800 mg/d orally

Study Arms

Experimental: nilotinib

nilotinib

Intervention: Drug: Nilotinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 8, 2019): 34
• Original Estimated Enrollment (submitted: September 19, 2008): 40
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years
• Histologically confirmed diagnosis of GIST that is unresectable and/or metastatic and therefore not amenable to surgery or combined modality with curative intent prior to or at Visit 1
• At least one measurable site of disease on CT/MRI scan at Visit 1, as defined by RECIST criteria (see Post Text Suppl 3 for details) The scans should be at maximum 2 weeks old. New scans are only required as baseline scans if they are older then approx. 2 weeks.
• WHO Performance Status of 0, 1 or 2

• Patients must have the following laboratory values (≥ LLN (lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of study medication.):

  1. Potassium ≥ LLN,
  2. Magnesium ≥ LLN,
  3. Phosphorus ≥ LLN,
  4. Total calcium (corrected for serum albumin) ≥ LLN

• Patients must have normal organ, electrolyte, and marrow function as defined below:

  1. Absolute Neutrophil Count (ANC) ≥ 1.5x 109/L;
  2. Platelets ≥ 100 x 109/L;
  3. ALT and AST ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if considered due to tumor;
  4. Alkaline phosphatase ≤ 2.5 x ULN unless considered due to tumor;
  5. Serum bilirubin ≤ 1.5 x ULN;
  6. Serum lipase and amylase ≤ 1.5 x ULN;
  7. Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min. (calculated creatinine clearance using Cockroft formula is acceptable)
• Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

• Prior treatment with nilotinib
• Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1 with the exception of imatinib targeted therapy as an adjuvant therapy
• Prior or concomitant malignancies requiring active treatment other than GIST with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ

• Impaired cardiac function at including any one of the following:

  1. LVEF < 45% or below the institutional LLN range (whichever is higher) as determined by echocardiogram at Visit 1
  2. Complete left bundle branch block
  3. Use of a ventricular paced cardiac pacemaker
  4. Congenital long QT syndrome or family history of long QT syndrome
  5. History of or presence of significant ventricular or atrial tachyarrhythmias
  6. Clinically significant resting bradycardia (< 50 beats per minute)
  7. QTc > 450 msec on screening ECG (using the QTcF formula). If QTc > 450 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc.
  8. Right bundle branch block plus left anterior hemiblock, bifascicular block
  9. Myocardial infarction within 12 months prior to Visit 1
  10. Other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension,)
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland, France, Germany, Italy
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT00756509
• Other Study ID Numbers: CAMN107DDE06; 2008-000358-11 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• URL: https://www.clinicalstudydatarequest.com

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: External Affairs, Novartis
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: March 2024