Imatinib for Gastrointestinal Stromal Cancer
Recruiting in Palo Alto (17 mi)
Overseen byReema Patel, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Reema A. Patel
Must be taking: Imatinib
Must not be taking: Warfarin, CYP3A drugs
Disqualifiers: PDGFRA D842V mutation, others
No Placebo Group
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?Imatinib can lead to long recurrence free survival in patients diagnosed with gastrointestinal stromal tumors (GIST); however side effects can significantly hinder quality of life for our patients. This study will use therapeutic drug monitoring to improve quality of life and symptoms and assess how many patients maintain therapeutic levels. Free drug levels and pharmokinetics of imatinib will also be monitored.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain drugs that affect liver enzymes (CYP3A or CYP3A4) or are on oral warfarin. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Imatinib for treating gastrointestinal stromal cancer?
Imatinib, a drug that targets specific cancer cell growth signals, has been shown to improve survival in patients with gastrointestinal stromal tumors (GISTs), especially when traditional chemotherapy is ineffective. Studies have reported good responses in cases of advanced GISTs, with many patients experiencing remission or disease stabilization.
12345Is imatinib safe for treating gastrointestinal stromal tumors?
Imatinib is generally considered safe for treating gastrointestinal stromal tumors, with most side effects being mild and occurring early in treatment. Serious side effects are rare, and the drug is well tolerated over long-term use.
678910What makes the drug imatinib unique for treating gastrointestinal stromal cancer?
Imatinib is unique because it specifically targets and inhibits the KIT protein, which is often mutated and overactive in gastrointestinal stromal tumors, leading to uncontrolled cell growth. This targeted approach is more effective than traditional chemotherapy, which generally has poor results for this type of cancer.
511121314Eligibility Criteria
Adults over 18 with a specific type of tumor called GIST and certain genetic mutations can join. They should be starting or have recently started taking Imatinib, have good performance status, and normal organ function. Those with uncontrolled illnesses, on warfarin, other cancer treatments within 6 months without disease evidence, or allergies to Imatinib cannot participate.Inclusion Criteria
I am 18 years old or older.
My organs are functioning normally.
My GIST tumor has a KIT or PDGFRA mutation, but not D842V.
+3 more
Exclusion Criteria
I have another type of cancer besides the one being treated.
I am not taking medication that strongly affects certain liver enzymes.
I am allergic to imatinib or similar drugs.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive imatinib with therapeutic drug monitoring to improve quality of life and symptoms
6 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing if monitoring the levels of the drug Imatinib in the blood can improve life quality for patients with gastrointestinal stromal tumors (GIST) while maintaining its effectiveness. It involves checking free drug levels and how the body processes the drug.
1Treatment groups
Experimental Treatment
Group I: Imatinib TDMExperimental Treatment1 Intervention
Patients with diagnosed gastrointestinal stromal tumor (GIST) who are currently being treated with imatinib.
Imatinib is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:
🇪🇺 Approved in European Union as Gleevec for:
- Chronic myeloid leukemia
- Gastrointestinal stromal tumors
- Dermatofibrosarcoma protuberans
- Systemic mastocytosis
- Hypereosinophilic syndrome
🇺🇸 Approved in United States as Gleevec for:
- Chronic myeloid leukemia
- Gastrointestinal stromal tumors
- Dermatofibrosarcoma protuberans
- Systemic mastocytosis
- Hypereosinophilic syndrome
🇨🇦 Approved in Canada as Glivec for:
- Chronic myeloid leukemia
- Gastrointestinal stromal tumors
- Dermatofibrosarcoma protuberans
- Systemic mastocytosis
- Hypereosinophilic syndrome
🇯🇵 Approved in Japan as Glivec for:
- Chronic myeloid leukemia
- Gastrointestinal stromal tumors
- Dermatofibrosarcoma protuberans
- Systemic mastocytosis
- Hypereosinophilic syndrome
🇨🇭 Approved in Switzerland as Gleevec for:
- Chronic myeloid leukemia
- Gastrointestinal stromal tumors
- Dermatofibrosarcoma protuberans
- Systemic mastocytosis
- Hypereosinophilic syndrome
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Markey Cancer CenterLexington, KY
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Who Is Running the Clinical Trial?
Reema A. PatelLead Sponsor
References
Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role? [2021]Imatinib resistance is associated with a poor prognosis in patients with gastrointestinal stromal tumors. Although novel tyrosine kinase inhibitors have improved outcomes in imatinib-resistant gastrointestinal stromal tumors, the role of resection remains unclear. We sought to investigate factors predictive of overall and progression-free survival in patients with imatinib-resistant gastrointestinal stromal tumors.
Patterns of progression in gastrointestinal stromal tumor treated with imatinib mesylate. [2022]Although most patients with gastrointestinal stromal tumor (GIST) treated with imatinib mesylate achieve remission or disease stabilization, a significant proportion show progressive disease (PD) with or without initial favorable responses. We evaluated and categorized the patterns of progression of metastatic or unresectable GIST treated with imatinib to identify the prognostic significance and contribution to further treatment decision-making.
Gastric GISTs. Personal experience. [2015]With term GIST is now defined a group of mesenchimal tumours of the gastrointestinal tract expressing immunopositivity for kit protein kinase (CD117). Surgical therapy remains the gold standard for these rare tumours. Imatinib Mesylate (STI-571) is a potent inhibitor of Kit Kinase activity and different reports demonstrated its efficacy in unresectable or metastatic Gists.
[Imatinib mesylate STI571 therapy for five patients with advanced gastrointestinal stromal tumors]. [2015]To explore the therapeutic effect of STI571(imatinib mesylate) on advanced gastrointestinal stromal tumors (GISTs).
Imatinib and gastrointestinal stromal tumor (GIST): a selective targeted therapy. [2019]Gastrointestinal stromal tumors are the most frequent mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by an anomalous receptor for a growth factor with tyrosine-kinase activity (c-kit). This anomaly causes a permanent activation of the receptor and uncontrolled cell growth. These tumors show a poor response to traditional chemotherapy drugs, and are thus associated with low survival in cases of advanced disease. Imatinib, a tyrosine kinase inhibitor, is an example of selective targeted oncologic therapy that induces improved survival in these patients. We discuss two cases of metastatic gastrointestinal stromal tumors with a good response to imatinib, and also review the pathophysiology and treatment-related outcome of this type of tumors. We include results from clinical phase-III studies.
The safety profile of imatinib in CML and GIST: long-term considerations. [2015]Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST) by targeting BCR-ABL and c-KIT tyrosine kinases, respectively. Indeed, imatinib has substantially changed the clinical management and improved the prognosis of both diseases. Treatment with imatinib is generally well tolerated, and the risk for severe adverse effects is low, generally occurring during the early phase of treatment and correlating with imatinib dose, phase of disease and patient's characteristics. This article summarises recent data on safety profile of imatinib for the treatment of CML and GIST, including long-term side effects. Prolonged treatment with imatinib in both diseases demonstrates excellent tolerability. There are few significant concerns and those that have emerged, like cardiotoxicity, have far turned out to be exaggerated.
Imatinib mesylate for the treatment of gastrointestinal stromal tumours: best monitored with FDG PET. [2022]The new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor, c-KIT, and has shown spectacular activity in patients with gastrointestinal stromal tumours (GISTs).
[The effect of imatinib for gastrointestinal tumor]. [2015]Long-term survival in patients with gastrointestinal stromal tumors (GIST) was very rare. Recently treatment with imatinib mesylate, a molecular targeted agent that inhibits the KIT tyrosine kinase receptor showed 81.6% of outstanding clinical response (PR 53.7%, SD 27.9%). Toxicities with daily dose of 400 mg and 600 mg, all patients had grade 1 or 2 toxicity. Grade 3 or higher toxicities occurred in 21.1% including edema, neutropenia, nausea, dermatitis, hepatitis and gastrointestinal hemorrhage. The drug was relatively safe overall.
A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. [2021]Targeting constitutively activated tyrosine kinases, such as BCR-ABL, in chronic myeloid leukaemia (CML) and c-KIT in gastrointestinal stromal tumours (GIST) has substantially changed the clinical management of both diseases. The introduction of imatinib, a tyrosine kinase inhibitor mainly targeting BCR-ABL, c-KIT and PDGFR, has profoundly improved the prognosis of both entities, while being surprisingly well tolerated. This article summarizes recent data on clinical efficacy as well as safety aspects of imatinib for treatment of CML and GIST, including a final benefit-risk assessment. Imatinib induces high rates of cytogenetic and molecular responses in all phases of CML and also has substantial activity in GIST patients. In both diseases, only a few adverse effects, such as musculoskeletal and joint pain, muscle cramps, oedema and gastrointestinal symptoms, occur. Most of these are grade I or II toxicities and generally occur during the early phase of treatment (i.e. within the first 2 years). Thus, in view of the low rates of severe toxicities and the extraordinary efficacy of the drug in both diseases, imatinib represents an oral drug with a high benefit-risk ratio for the treatment of CML and GIST.
Use of imatinib mesylate in gastrointestinal stromal tumours: Pan-Birmingham Cancer Network experience. [2015]Imatinib mesylate, a selective tyrosine kinase receptor inhibitor of KIT and PDGFRalpha, is currently licensed for the treatment of unresectable or metastatic gastrointestinal stromal tumours (GISTs), which are KIT positive. Partial response rates in 65% of patients and stable disease in 20% of patients are typically seen. The aim of this study was to assess the effectiveness and toxicity of an unselected cohort of patients treated with imatinib mesylate and to compare these results with published data.
Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. [2022]Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour.
Outcomes of patients with metastatic gastrointestinal stromal tumors (GIST) treated with multi-kinase inhibitors other than imatinib as first-line treatment. [2022]Imatinib is the standard first-line therapy in metastatic gastrointestinal stromal tumours (GIST). Investigational multi-kinase inhibitors (MKIs) such as nilotinib, dasatinib or masitinib have been tested as first-line therapies in phase II/III studies. This might theoretically result either in increased survival or in early emergence of resistance to approved MKIs.
Role of imatinib mesylate (Gleevec/Glivec) in gastrointestinal stromal tumors. [2015]Gastrointestinal stromal tumors are soft tissue sarcomas of the gastrointestinal tract that originate from mesenchymal cells. Advances in the systemic therapy of gastrointestinal stromal tumors are highlighted by the rapid development and approval of the molecularly targeted therapy imatinib mesylate (Gleevec/Glivec). Mutations of the KIT gene are known to be present in most gastrointestinal stromal tumors and result in gain of function, with permanent activation of the expressed KIT receptor in the absence of binding of the stem cell factor ligand. Imatinib is the first rationally designed selective inhibitor of specific protein tyrosine kinases, including KIT. Inhibiting the downstream signaling of KIT switches the cell balance into apoptosis. Although complete responses have seldom been seen up until now, imatinib has proven to be extremely effective in the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumors.
Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. [2022]Gastrointestinal stromal tumours (GISTs) are rare tumours of the gastrointestinal tract characterised by cell-surface expression of the tyrosine kinase KIT (CD117). No effective systemic treatment is available. Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. We did a phase I study to identify the dose-limiting toxic effects of imatinib in patients with advanced soft tissue sarcomas including GISTs.