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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests imatinib, a medication for individuals with gastrointestinal stromal tumors (GIST), to determine if monitoring drug levels improves quality of life and manages side effects. Researchers aim to discover whether this approach keeps patients symptom-free longer while maintaining the appropriate drug levels in the body. Individuals with a confirmed GIST diagnosis who are currently taking imatinib or will start soon may be suitable for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that imatinib is likely to be safe for humans?

Research has shown that imatinib is generally safe for many patients with gastrointestinal stromal tumors (GIST). More than half of patients with advanced GIST respond well to imatinib. However, side effects such as swelling, muscle cramps, and tiredness can occur.

One study found that patients who took imatinib for three years had better survival rates than those who took it for only one year. This finding suggests that longer use of imatinib can be beneficial, but managing side effects remains important.

Overall, imatinib is well-tolerated, but monitoring and managing side effects is necessary to maintain a good quality of life. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Imatinib is unique because it targets specific proteins that play a key role in the growth of gastrointestinal stromal tumors (GIST). Unlike traditional chemotherapy, which attacks all rapidly dividing cells, imatinib specifically inhibits the activity of the proteins produced by the mutated KIT or PDGFRA genes that drive the cancer. This targeted approach not only increases the effectiveness of the treatment but also reduces side effects, making it a promising option for patients with GIST. Researchers are excited because it represents a more precise and potentially more tolerable treatment option compared to conventional therapies.

What is the effectiveness track record for Imatinib in treating gastrointestinal stromal tumors?

Research has shown that imatinib, the treatment under study in this trial, effectively treats gastrointestinal stromal tumors (GIST). Studies indicate that imatinib improves health outcomes, with more than half of patients experiencing long-lasting benefits. Specifically, one study found that imatinib helped more than 10% of patients with advanced GIST live for 20 years. Additionally, taking imatinib for three years reduced the chances of cancer recurrence and improved overall survival. These findings support imatinib's potential to effectively manage GIST. ^{2 5 6 7 8}

Who Is on the Research Team?

Reema Patel, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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 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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425007410

Twenty-year survival of advanced gastrointestinal stromal ... With >18 years of median follow-up, imatinib provides 20-year survival for >10% of patients with advanced GIST. •. GIST with KIT exon 11 mutations, ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa020461

Efficacy and Safety of Imatinib Mesylate in Advanced ... Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00116935

NCT00116935 | Study Comparing 12 Months Versus 36 ... In this study, patients who have been diagnosed with gastrointestinal stromal tumor (GIST) will be randomly allocated in a 1:1 ratio to receive imatinib ( ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2711891

Efficacy and Tolerability of 5-Year Adjuvant Imatinib ... Importance Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37079223/

Improved Efficacy of First-Line Imatinib in Advanced ... This study provides an update on outcomes of imatinib in the treatment of advanced GIST patients and demonstrates improved clinical outcomes

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11064882/

Safety outcomes of low versus high dose imatinib mesylate in ... Safety outcomes of low versus high dose imatinib mesylate in patients with advanced, metastatic, or nonresectable gastrointestinal stromal tumors: A systematic ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01172548

Safety and Efficacy Evaluation of Two Year Imatinib ... In summary, clinical trials have shown that imatinib produces clinical benefit in most patients with unresectable or metastatic GIST and extends median survival ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7260691/

Survival Outcomes Associated With 3 Years vs 1 Year of ... Three years of treatment with adjuvant imatinib was associated with improved OS compared with 1 year of imatinib in patients with high-risk GIST.