Clinical trial NCT00154388: Phase II Study of Imatinib Mesylate in Patients With Life Threatening Malignant Rare Diseases
Official title: Phase II Study of Imatinib Mesylate in Patients With Life Threatening Malignant Rare Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Life Threatening Diseases
Keywords: adenocarcinoma
leiomyosarcoma
angiosarcoma
synovial sarcoma
myelodysplastic syndrome/HES
CMML
multiple myeloma
embryonal rhabdomyosarcoma
endometrial sarcoma
adenoid cystic carcinoma
fibromatosis
ductal invasive breast carcinoma
chondrosarcoma
pleural tumor
brenner tumor
ewing sarcoma
round cell tumor
seminoma
thymic carcinoma
malignant melanoma
fibrosarcoma breast
dermatofibrosarcoma protuberans
DFSP
ovarian stromal tumor
osteosarcoma
chorioideal melanoma
hemangiopericytoma
myelofibrosis
liposarcoma
SCLC
small cell lung carcinoma
hypereosinophilic syndrome
chronic myelo-monocytic leukemia
neurofibrosarcoma
mesothelioma
malignant mesenchymoma
malignant schwannoma
mast cell leukemia / mastocytosis
renal cell carcinoma
malignant histocytoma
chordoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 185
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Exploratory study to examine the effect(s) of Imatinib mesylate treatment on life threatening rare diseases with known associations to one or more Imatinib mesylate -sensitive tyrosine kinases, and to identify the contribution of specific protein tyrosine kinases (PTKs) of that specific disease.


Eligibility criteria: Inclusion Criteria:

* Patients ≥ 15 years of age
* Life threatening disease documented by conventional criteria to be resistant to standard, approved therapy.
* Experimental documentation of functional significance of either Abl, Kit (CD117), or PDGF-R in the relevant target tissue (preferably on a sample taken within 6 weeks of study entry).
* ECOG Performance status of 0, 1, or 2.
* Adequate end organ function defined as: total bilirubin \< 1.5 x ULN, SGOT and SGPT \< 2.5 x UNL (or \< 5 x ULN for patients with hepatic disease), creatinine \< 1.5 x ULN, ANC \> 1.5 x 109/L, platelets \> 100 x 109/L.
* Negative serum or urine pregnancy test for women of child bearing potential (WOCBP) within 7 days of study initiation. Post menopausal women must have experienced amenorrhea for at least 12 months. Male and female patients must use effective birth control methods throughout the study and for up to 3 months after study discontinuation.
* Life expectancy of more than 3 months.
* Written, voluntary, informed consent for retrieval, evaluation and investigational use of tissue samples.

Exclusion Criteria:

* Patients who have received any other investigational agent within 28 days of study initiation.
* Patients with another primary malignancy except if other primary malignancy is neither currently clinically significant nor requiring active intervention.
* Patients with Grade III/IV cardiac problems defined by the New York Heart Association Criteria (e.g. congestive heart failure, myocardial infarction within 6 months of study).
* Female patients who are pregnant or breast-feeding.
* Patients who have another severe and/or life threatening medical disease.
* Patients with acute or known chronic liver disease (e.g. chronic active hepatitis, cirrhosis).
* Patients with a known diagnosis of the human immunodeficiency virus ((HIV) infection.
* Patients who have received chemotherapy within 4 weeks (6 weeks allowed for nitrosourea, mitomycin-C or any antibody therapy) prior to study entry.
* Patients who have had major surgery within 2 weeks prior to study entry.
* Patients with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: To examine the effect(s) of Imatinib mesylate treatment on life threatening rare diseases with known associations to one or more Imatinib mesylate-sensitive tyrosine kinases
measure: To identify the contribution of specific protein tyrosine kinases (PTKs) of that specific disease
Secondary outcomes:
measure: To assess the safety and tolerability of Imatinib mesylate
measure: To evaluate the pharmacokinetic profile of Imatinib mesylate
measure: To assess, where feasible, the functional significance of relevant signal-transduction components in target tissues
Other outcomes:
Locations:
Study officials:
affiliation: Oregon Health and Science University
name: Michael Heinrich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chugh R, Wathen JK, Maki RG, Benjamin RS, Patel SR, Meyers PA, Priebat DA, Reinke DK, Thomas DG, Keohan ML, Samuels BL, Baker LH. Phase II multicenter trial of imatinib in 10 histologic subtypes of sarcoma using a bayesian hierarchical statistical model. J Clin Oncol. 2009 Jul 1;27(19):3148-53. doi: 10.1200/JCO.2008.20.5054. Epub 2009 May 18.