Imatinib for Gastrointestinal Stromal Cancer

Overseen By Yvonne A Taul, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Reema A. Patel

Must be taking: Imatinib

Must not be taking: Warfarin, CYP3A drugs

Disqualifiers: PDGFRA D842V mutation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

28 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{6 7 8 9 10}

What 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. ^{5 11 12 13 14}

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.

Research Team

Reema Patel, MD

Principal Investigator

University of Kentucky

Eligibility 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

My organs are functioning normally.

My GIST tumor has a KIT or PDGFRA mutation, but not D842V.

I am fully active or can carry out light work.

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.

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

Treatment Details

Interventions

• Imatinib

Trial Overview 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.

Participant Groups

Group I: Imatinib TDM Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Reema A. Patel

Lead Sponsor

Trials

2

Recruited

210+

Findings from Research

In a study of 84 patients with imatinib-resistant gastrointestinal stromal tumors, surgical resection was found to significantly improve progression-free survival, with a hazard ratio of 0.50, indicating a 50% reduction in the risk of disease progression after surgery.

Although resection did not show a significant impact on overall survival (hazard ratio 0.62), the findings suggest that surgery may still be beneficial for selected patients, especially considering the median overall survival after developing resistance was 51 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role? Sutton, TL., Walker, BS., Billingsley, KG., et al.[2021]

In a study of 62 patients with gastrointestinal stromal tumors (GIST) treated with imatinib mesylate for a median of 26 months, four distinct patterns of disease progression were identified, which have different implications for patient outcomes.

Patients with new cystic lesions (NCL) showed a significantly higher response to increased doses of imatinib and had better overall survival compared to those with new solid lesions (NSL) or general progression (GP), highlighting the importance of recognizing progression patterns for treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of progression in gastrointestinal stromal tumor treated with imatinib mesylate. Ryu, MH., Lee, JL., Chang, HM., et al.[2022]

In a study of 12 cases of gastric mesenchymal tumors, 67% were identified as GISTs, with gastrointestinal bleeding being the most common symptom and a significant number presenting with palpable abdominal masses.

Imatinib Mesylate showed a good response in a case of metastatic GIST, highlighting its potential as a palliative treatment option, especially when combined with surgical resection for advanced lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric GISTs. Personal experience. Mingolla, GP., Riccio, PA., Linguerri, R., et al.[2015]

STI571 (imatinib mesylate) has shown significant therapeutic effects in reducing tumor size in patients with advanced gastrointestinal stromal tumors (GISTs) who had previously failed other treatments, based on a retrospective analysis of 5 cases.

The treatment was well-tolerated, with no serious drug-related side effects reported, highlighting its potential as a safe and effective alternative to conventional chemotherapy for advanced GISTs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Imatinib mesylate STI571 therapy for five patients with advanced gastrointestinal stromal tumors]. Shen, KT., Hou, YY., Qin, XY., et al.[2015]

Gastrointestinal stromal tumors (GISTs) are often resistant to traditional chemotherapy, leading to low survival rates in advanced cases, but they originate from cells with a specific growth factor receptor anomaly that causes uncontrolled growth.

Imatinib, a targeted therapy that inhibits the abnormal tyrosine kinase activity in GISTs, has shown to significantly improve survival outcomes, as demonstrated in two case studies and supported by phase-III clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib and gastrointestinal stromal tumor (GIST): a selective targeted therapy. Fernández, A., Aparicio, J.[2019]

Imatinib mesylate is the standard first-line treatment for chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST), effectively targeting specific tyrosine kinases and significantly improving patient prognosis.

The treatment is generally well tolerated with a low risk of severe side effects, and long-term use shows excellent tolerability, with concerns like cardiotoxicity being largely exaggerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of imatinib in CML and GIST: long-term considerations. Thanopoulou, E., Judson, I.[2015]

In a study of 16 patients with advanced gastrointestinal stromal tumors (GISTs) treated with imatinib mesylate, FDG PET imaging effectively identified treatment responders within just one week, showing a 65% reduction in SUV for responders compared to a 16% increase for non-responders.

FDG PET not only predicted treatment outcomes with a high sensitivity of 93% but also provided better early response evaluation than traditional imaging methods, indicating its potential as a valuable tool for monitoring treatment efficacy and managing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib mesylate for the treatment of gastrointestinal stromal tumours: best monitored with FDG PET. Jager, PL., Gietema, JA., van der Graaf, WT.[2022]

Imatinib mesylate has shown a high clinical response rate of 81.6% in patients with gastrointestinal stromal tumors (GIST), with 53.7% achieving a partial response and 27.9% having stable disease.

While most patients experienced only mild toxicities (grade 1 or 2), 21.1% had more severe side effects (grade 3 or higher), indicating that imatinib is relatively safe but can still cause significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. Mizunuma, N.[2015]

Imatinib, a tyrosine kinase inhibitor, has significantly improved the prognosis for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST), showing high rates of cytogenetic and molecular responses across all phases of CML.

The drug is well tolerated, with only mild adverse effects such as joint pain and gastrointestinal symptoms, primarily occurring in the first two years of treatment, making it a safe and effective oral option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. Wolf, D., Rumpold, H.[2021]

In a study of 39 patients with gastrointestinal stromal tumors (GISTs) treated with imatinib mesylate, 59% achieved a partial response and 18% had stable disease, demonstrating effectiveness consistent with published data.

Imatinib mesylate was well tolerated, with only mild side effects reported, such as peri-orbital edema and skin rash, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of imatinib mesylate in gastrointestinal stromal tumours: Pan-Birmingham Cancer Network experience. Wong, DW., Lupton, SC., Bhatt, L., et al.[2015]

In a randomized phase III trial involving 713 patients, adjuvant treatment with imatinib significantly improved recurrence-free survival after surgical resection of localized gastrointestinal stromal tumors, with only 8% recurrence in the imatinib group compared to 20% in the placebo group.

Imatinib was well tolerated, with manageable side effects, indicating it is a safe option for patients following surgery for gastrointestinal stromal tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Dematteo, RP., Ballman, KV., Antonescu, CR., et al.[2022]

In a study of 46 patients with metastatic gastrointestinal stromal tumors (GIST), those who received investigational multi-kinase inhibitors (MKIs) as first-line treatment followed by imatinib as second-line therapy had a median time to second relapse of 48.7 months, which is longer than historical data for imatinib as first-line treatment.

The findings suggest that using MKIs other than imatinib in the first line does not compromise the efficacy of imatinib in subsequent treatment lines, indicating a potential benefit in treatment strategy for GIST patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of patients with metastatic gastrointestinal stromal tumors (GIST) treated with multi-kinase inhibitors other than imatinib as first-line treatment. Boilève, A., Dufresne, A., Chamseddine, A., et al.[2022]

Imatinib mesylate (Gleevec/Glivec) is a targeted therapy that effectively treats gastrointestinal stromal tumors (GISTs) by inhibiting the mutated KIT gene, which is responsible for tumor growth.

While complete responses are rare, imatinib has shown significant efficacy in patients with unresectable or metastatic GISTs, leading to increased apoptosis in tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of imatinib mesylate (Gleevec/Glivec) in gastrointestinal stromal tumors. de Jong, FA., Verweij, J.[2015]

In a phase I study involving 40 patients (36 with GISTs), imatinib at a dose of 400 mg twice daily was found to be well tolerated and effective, with significant tumor growth inhibition observed in most patients.

The study demonstrated that imatinib led to 19 confirmed partial responses and improvements in symptoms for 24 out of 27 symptomatic patients, highlighting its potential as a targeted treatment for GISTs based on the inhibition of the KIT tyrosine kinase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. van Oosterom, AT., Judson, I., Verweij, J., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role? [2021]

2. England pubmed.ncbi.nlm.nih.gov

Patterns of progression in gastrointestinal stromal tumor treated with imatinib mesylate. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Gastric GISTs. Personal experience. [2015]

4. China pubmed.ncbi.nlm.nih.gov

[Imatinib mesylate STI571 therapy for five patients with advanced gastrointestinal stromal tumors]. [2015]

5. Spain pubmed.ncbi.nlm.nih.gov

Imatinib and gastrointestinal stromal tumor (GIST): a selective targeted therapy. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

The safety profile of imatinib in CML and GIST: long-term considerations. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Imatinib mesylate for the treatment of gastrointestinal stromal tumours: best monitored with FDG PET. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. [2015]

9. New Zealand pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Use of imatinib mesylate in gastrointestinal stromal tumours: Pan-Birmingham Cancer Network experience. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Outcomes of patients with metastatic gastrointestinal stromal tumors (GIST) treated with multi-kinase inhibitors other than imatinib as first-line treatment. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Role of imatinib mesylate (Gleevec/Glivec) in gastrointestinal stromal tumors. [2015]

14. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. [2022]