Nilotinib 800 Mg And Imatinib 800 Mg For The Treatment Of Patients With Gastrointestinal Stromal Tumors (Gist) Refractory To Imatinib 400 Mg

NCT00751036 | Terminated Phase 3 Results

• 2 other identifiers: CAMN107DBR012010-019806-18
• Study Type: interventional
• Target: 94
• Locations: 9 countries
• Sites: 32

Brief Summary

The study will investigate the comparative efficacy and safety of two oral inhibitors of Kit and PDGFR: nilotinib 400 mg bid, a novel agent, and imatinib 400 mg bid, an approved agent with an established efficacy.

Conditions

Gastrointestinal Stromal Tumors

Keywords

GIST

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.

  24 months

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  every 2 months until 24 months (end of study)

• Time to Treatment Failure

  Time from date of radomization to the earliest date of the first objective tumor, death or discontinuation, assesed until 24 months.

• Overall Survival (OS)

  time from the date of randomization to the date of death due to any cause or the date of last contact prior to or on the date of data cutoff, assesed until 24 months.

Study Arms (2)

Nilotinib

EXPERIMENTAL

Patients who were assigned to this treatment group received 400 mg. nilotinib bid.

Drug: Nilotinib

Imatinib

ACTIVE COMPARATOR

Patients who were assigned to this treatment group received 400 mg. imatinib bid.

Drug: Imatinib

Interventions

Nilotinib DRUG

Nilotinib hard gel capsules were supplied to the Investigators at dose strengths of 200 mg. Nilotinib is a novel agent, which has been approved for the treatment of chronic phase and accelerated phase Philadelphia-chromosome-positive CML in adult patients resistant to or intolerant to prior therapy that included imatinib.

Also known as: Tasigna

Nilotinib

Imatinib DRUG

Imatinib tablets were supplied at 100 mg and/or 400 mg dose strength. Imatinib is an approved agent for GIST. Efficacy of imatinib at a dose of 400 mg bid has been established in the setting of disease progression after the use of the conventional dose (400 mg qd).

Imatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide a written informed consent.
• Male or female patients ≥ 18 years of age.
• Histologically confirmed diagnosis of GIST of any anatomical location, which is unresectable and/ or metastatic or recurrent.
• Documented disease progression according to RECIST 1.0. Documentation of progression required by either 2 CT scans or 2 MRI scans within 6 months prior to randomization (one image will document the lesion and the other will document the progression by lesion(s) growth or the presence of new lesion(s)). The interval between the 2 images should be no greater than 6 months apart. Scans will be provided to the selected imaging CRO.
• Documented disease progression must occur while on imatinib 400 mg PO q.d. Imatinib therapy could be for (1) unresectable GIST; (2) metastatic GIST; or (3) recurrent GIST while on imatinib adjuvant therapy or recurrent GIST post adjuvant imatinib therapy.
• Positive immunohistochemical staining for c-KIT (CD117) or negative staining for KIT, but with either positive staining for DOG1 or an identified mutation on KIT or PDGFR genes.
• Presence of at least one measurable lesion according to RECIST 1.0, defined as a lesion that can be accurately measured in at least one dimension (longest diameter) as ≥ 20 mm with conventional techniques (conventional CT or MRI scan) or as ≥ 10 mm with spiral CT scan. Lesions in previously irradiated areas can be considered measurable only if they have demonstrated clear evidence of progression since the radiotherapy.
• A performance status of 0, 1 or 2 according to the Eastern Cooperative Oncology Group (ECOG) scale (Oken et al 1982)(Appendix A).
• Adequate organ function, as indicated by all of the following:
• White blood cell (WBC) count ≥ 3500/mm3;
• Absolute neutrophil count (ANC) ≥1500/mm3;
• Hemoglobin ≥ 9.0 g/dL;
• Platelet count ≥ 100 x 109/L;
• Total bilirubin ≤ 1.5 X ULN (\< 3.0 X ULN if related to disease);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the ULN, unless liver metastases present, in which case AST and ALT have to be ≤ 5 times the ULN;

You may not qualify if:

• Prior use of imatinib doses higher than 400 mg q.d. or prior use of any other tyrosine-kinase inhibitor.
• Tumor progression after stopping imatinib 400 mg q.d.
• No investigational cytotoxic drug ≤ 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to the Screening Visit (V100) is allowed with the exception of imatinib therapy.
• Cytotoxic, or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response modifiers, or radiotherapy.
• If the only measurable lesion was previously irradiated and has not shown clear evidence of progression since the radiotherapy, the patient cannot be included.
• Serious uncontrolled concomitant medical or psychiatric illness.
• Impaired cardiac function including any one of the following:
• LVEF \< 45% or below the institutional lower limit of the normal range (whichever is higher) confirmed by ECHO or Muga
• Inability to determine the QT interval on ECG
• Complete left bundle branch block
• Right bundle branch block plus left anterior or posterior hemiblock
• Use of a ventricular-paced pacemaker
• Congenital long QT syndrome or a known family history of long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (\<50 bpm);

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (32)

Novartis Investigative Site

Buenos Aires, Buenos Aires, C1264AAA, Argentina

Location

Novartis Investigative Site

Caba, Buenos Aires, C1426ANZ, Argentina

Location

Novartis Investigative Site

Fortaleza, Ceará, 60430-230, Brazil

Location

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Novartis Investigative Site

Divinópolis, Minas Gerais, 35500-000, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

Location

Novartis Investigative Site

Natal, Rio Grande do Norte, 59040-000, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Novartis Investigative Site

Barretos, São Paulo, 14784-400, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01221-020, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Montreal, Quebec, H2L 4M1, Canada

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Guangzhou, 510080, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Shanghai, 200433, China

Location

Novartis Investigative Site

Mexico City, Mexico City, 06720, Mexico

Location

Novartis Investigative Site

Moscow, 115478, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620036, Russia

Location

Novartis Investigative Site

Hwasun-gun, Jeollanam-do, 519-809, South Korea

Location

Novartis Investigative Site

Daegu, 705-717, South Korea

Location

Novartis Investigative Site

Seoul, 138-736, South Korea

Location

Novartis Investigative Site

Seoul, 139-706, South Korea

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Khon Kaen, 40002, Thailand

Location

Novartis Investigative Site

Songkhla, 90110, Thailand

Location

Novartis Investigative Site

Caracas, Distrito Federal, 1010, Venezuela

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

nilotinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Limitations and Caveats

Patients were limited (planned 300, Actual 94). Early termination of study; not sufficient power to test the original primary hypothesis with respect to PFS. Only descriptive analyses were carried out for this study.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2008
• First Posted: September 11, 2008
• Study Start: June 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: March 26, 2014
• Results First Posted: March 26, 2014

Record last verified: 2014-02

Locations

AR (2); TH (4); KR (4); CA (1); CN (6); VE (1); ME (1); RU (3); BR (10)