ocalized gastrointestinal stromal tumors (GIST): an exploratory open-label, multicenter, single-arm phase II study to evaluate the efficacy of 2 years of adjuvant nilotinib treatment following at least 1 year of adjuvant imatinib mesylate

Phase 1

• Conditions: localized gastrointestinal stromal tumors (GIST); MedDRA version: 13.1Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2010-022713-26-DE
• Lead Sponsor: ovartis Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-03-30
• Study Completion: 2011-05-02
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

1.Age = 18 yrs.
2.Histologically documented diagnosis of GIST. KIT-negative tumors morphologically compatible with GIST may be entered provided that the tumors contain either KIT or PDGFRa mutation(s).
3.Local disease (i.e. disease without distant metastases and/or peritoneal/intra-abdominal spread), completely excised through adequate surgery (R0 or R1 resection).
4.WHO Performance status 0, 1 or 2.
5.Patients with >20% of risk of recurrence, according to Miettinen classification (low and very low risk GIST are not eligible):
a.The final patient selection criteria will be based on anatomical site, size, mitotic index and tumor rupture. Eligible patients will have:
b.tumors > 5 cm with > 5 mitoses/50 high power fields
c.tumors > 10 cm
d.tumors with > 10 mitoses/50 high power fields
e.non-gastric tumors of 2-5 cm with > 5mitoses/50 high power fields
f.tumors of 5-10 cm of non-gastric origin
g.tumor rupture.
6.Patients have received imatinib (400 mg) for at least 12 months (a maximum 3 months time interval is allowed between the last date of imatinib administration and the first date of nilotinib administration). Imatinib dosing up to 600 mg/d, based on individual imatinib plasma levels, are allowed and/or patients have received imatinib at lower doses (300-400 mg) and showed intolerance to the drug.
7.Multiple surgical interventions are allowed, as long as the disease was inadequately excised before definitive surgery or there was a true local relapse.
8.Adequate end organ function as defined by:
a.Total bilirubin < 1.5 x ULN (upper limit of normal)
b.SGOT(AST) and SGPT(ALT) < 2.5 x ULN
c.Serum amylase and lipase = 1.5 x ULN
d.Alkaline phosphatase = 2.5 x ULN
e.Serum creatinine < 1.5 x ULN.
9.Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication:
a.Potassium
b.Magnesium
c.Phosphate
d.Total calcium (corrected for serum albumin).
10.Patients must have normal marrow function as defined below:
a.Absolute Neutrophil Count (ANC) = 1.5 x 109/L
b.Hemoglobin = 9.0 g/dL
c.Platelets = 100 x 109/L.
11.Negative pregnancy test for female patients; consent not to generate during treatment period for all patients.
12.Free, voluntary written informed consent obtained prior to any screening procedures.
13.Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Previous radiation therapy for GIST, chemotherapy for GIST or molecular treatment for GIST other than imatinib.
2.Impaired cardiac function including any one of the following:
a.LVEF < 45% or below the institutional lower limit of the normal range (whichever is higher).
b.Inability to determine the QT interval on echocardiogram (ECG).
c.Complete left bundle branch block.
d.Right bundle branch block plus left anterior or posterior hemiblock.
e.Use of a ventricular-paced pacemaker.
f.Congenital long QT syndrome or a known family history of long QT syndrome.
g.History of or presence of clinically significant ventricular or atrial tachyarrhythmias.
h.Clinically significant resting bradycardia (< 50 beats per minute).
i.QTc > 450 msec at baseline ECG (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
j.History or clinical signs of myocardial infarction within 1 year of study entry.
k.History of unstable angina within 1 year of study entry.
l.Other clinically significant heart disease (e.g. congestive heart failure or uncontrolled hypertension).
3.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. uncontrolled diabetes, uncontrolled infection).
4.History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
5.Acute or chronic liver, pancreatic, or severe renal disease considered unrelated to study disease.
6.History of significant congenital or acquired bleeding disorder unrelated to cancer.
7.History of other active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ.
8.Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
9.Patients actively receiving therapy with herbal medicines that are CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John’s Wort, and Ginkgo.
10.Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug. (Please see http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents that prolong the QT interval.)
11.Impairment of Gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
12.Women who are pregnant, breast feeding or adults of reproductive potential not employing an effective method of birth control. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of contraception during the study and for up to three months follo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified