Regorafenib for GIST

Overseen By Neeta Somaiah, M D

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: TKI other than imatinib

Disqualifiers: Uncontrolled hypertension, Cardiac disease, Bleeding disorders, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether regorafenib (also known as Stivarga, BAY 73-4506, or Regonix) can help control gastrointestinal stromal tumors (GIST), a type of cancer affecting the digestive system. It targets individuals whose GIST has spread or cannot be surgically removed and whose disease has progressed despite imatinib treatment. Eligible participants must have a specific mutation in the tumor and have experienced disease progression despite treatment. Participants must stop taking imatinib at least 5 days before starting the trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants stop taking imatinib at least 5 days before starting the study drug. The protocol does not specify about other medications, so it's best to discuss your current medications with the trial team.

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

Research has shown that regorafenib is generally safe for people with gastrointestinal stromal tumors (GIST). The FDA has approved this medication for treating advanced colorectal cancer and GIST when other treatments have failed. Studies have found that side effects are common but usually occur early in the treatment and typically do not worsen over time. Monitoring for side effects is crucial, especially in the first two months.

Some patients experience strong side effects that may require dose adjustments. However, healthcare providers can manage these side effects with careful monitoring and support. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Regorafenib is unique because it targets multiple pathways crucial for tumor growth and survival, including angiogenesis, which is the formation of new blood vessels that supply the tumor. Unlike existing treatments for gastrointestinal stromal tumors (GIST) that primarily target specific mutations, Regorafenib acts on a broader range of targets, potentially offering a solution for tumors that have developed resistance to standard treatments like imatinib and sunitinib. This multi-target approach could provide a new option for patients whose cancers have stopped responding to current therapies, making researchers eager to explore its full potential.

What evidence suggests that regorafenib might be an effective treatment for GIST?

Research shows that regorafenib, the treatment under study in this trial, effectively treats gastrointestinal stromal tumors (GIST) when other treatments, such as imatinib and sunitinib, stop working. Studies have found that regorafenib helps control the disease by targeting several proteins that promote tumor growth. Evidence suggests that regorafenib serves as an approved third-choice treatment for advanced GIST, used after other treatments fail. This treatment has shown promise in managing the disease, providing another option for patients when other therapies are ineffective. ^{1 6 7 8 9}

Who Is on the Research Team?

Neeta Somaiah, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with specific types of Gastrointestinal Stromal Tumors (GIST) that have worsened on imatinib treatment. They must have certain mutations or a deficiency in SDHB, measurable disease, and their major organs need to function well. Pregnant women, those with severe heart conditions, uncontrolled hypertension, recent bleeding events or surgeries are excluded.

Inclusion Criteria

I have a tumor that can be measured and is at least 1 cm in size.

My GIST tumor has a specific mutation or lacks SDHB as confirmed by a biopsy.

I agree to use effective birth control or abstain from sex during the study.

Exclusion Criteria

Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.

My high blood pressure is not controlled even with medication.

I do not have serious heart conditions such as severe heart failure, recent heart attacks, or unstable chest pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive regorafenib as a second-line treatment for GIST with specific mutations

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Regorafenib

Trial Overview The trial is testing Regorafenib's effectiveness for controlling GIST after the first-line treatment fails. It's for patients who've seen their cancer progress despite taking imatinib and focuses on particular genetic variations of the tumor.

How Is the Trial Designed?

Group I: Regorafenib Experimental Treatment 1 Intervention

Regorafenib is already approved in United States, European Union for the following indications:

Approved in United States as Stivarga for:

• Metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma (HCC)

Approved in European Union as Stivarga for:

• Metastatic colorectal cancer
• Gastrointestinal stromal tumors (GIST)
• Hepatocellular carcinoma (HCC)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

In a phase II trial involving 34 patients with advanced GIST who had previously failed imatinib and sunitinib, regorafenib demonstrated a clinical benefit rate of 79%, indicating significant efficacy in managing this challenging condition.

The median progression-free survival for patients on regorafenib was 10.0 months, with common side effects including hypertension and hand-foot-skin reactions, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. George, S., Wang, Q., Heinrich, MC., et al.[2022]

Regorafenib is an effective treatment for advanced gastrointestinal stromal tumors (GISTs) after patients have not responded to imatinib and sunitinib, showing significant improvement in progression-free survival and disease control rates compared to placebo in the phase III GRID trial.

The drug has a manageable safety profile, with common side effects including hand-foot skin reactions, hypertension, diarrhea, and fatigue, which can often be addressed with dose adjustments or supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib: A Review of Its Use in Patients with Advanced Gastrointestinal Stromal Tumours. Shirley, M., Keating, GM.[2018]

Regorafenib has been established as the standard treatment for advanced gastrointestinal stromal tumors (GIST) that do not respond to imatinib and sunitinib, providing a crucial option for patients with refractory disease.

The development of small molecule tyrosine kinase inhibitors like imatinib has significantly improved survival rates for patients with metastatic GIST, but challenges remain for those whose disease does not respond to these initial therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting gastrointestinal stromal tumors: the role of regorafenib. Schroeder, B., Li, Z., Cranmer, LD., et al.[2020]

In a phase III trial, regorafenib significantly improved median progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST), increasing it by more than five times compared to best supportive care alone.

While regorafenib is linked to some adverse events, it is generally well tolerated when proper dose modifications and precautions are implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib: a guide to its use in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib and sunitinib. Lyseng-Williamson, KA.[2018]

Regorafenib is an effective treatment for advanced gastrointestinal stromal tumors (GIST) in patients who have not responded to previous therapies like imatinib and sunitinib, as demonstrated in a pivotal Phase III trial.

The US FDA approved regorafenib in February 2013 based on evidence showing significant improvement in progression-free survival for patients taking the drug compared to those on a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib in gastrointestinal stromal tumors. Sirohi, B., Philip, DS., Shrikhande, SV.[2014]

In a 5-year study involving 341 patients treated with apremilast for psoriasis or psoriatic arthritis, no new safety concerns were identified, with no cases of serious adverse events like vasculitis or malignancies reported.

The incidence rates of opportunistic and serious infections in patients taking apremilast were comparable to those receiving other oral treatments, suggesting that apremilast has a similar long-term safety profile to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Apremilast in Patients with Psoriasis and Psoriatic Arthritis: Findings from the UK Clinical Practice Research Datalink. Persson, R., Cordey, M., Paris, M., et al.[2022]

Tofacitinib, a selective Janus kinase inhibitor, shows promising efficacy in treating various dermatological conditions such as psoriasis, alopecia areata, vitiligo, and atopic dermatitis, based on a review of 43 studies.

Despite its potential benefits, there are safety concerns regarding tofacitinib's overall profile, indicating that further research is needed to establish a favorable risk-to-benefit ratio for its use in dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib, an Oral Janus Kinase Inhibitor: Perspectives in Dermatology. Kostovic, K., Gulin, SJ., Mokos, ZB., et al.[2018]

Tofacitinib at doses of 3 mg or higher taken twice daily showed significant efficacy in treating active rheumatoid arthritis, with ACR20 response rates reaching up to 71.9% by week 12, compared to 22.0% for placebo.

The treatment was generally well-tolerated, with manageable side effects, the most common being urinary tract infections and diarrhea, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Fleischmann, R., Cutolo, M., Genovese, MC., et al.[2022]

Tofacitinib is an orally active immunosuppressant developed for various conditions, including rheumatoid arthritis and inflammatory bowel disease, by specifically inhibiting JAK3, a key player in immune cell signaling.

The drug's mechanism of action involves blocking cytokine signal transduction, which is crucial for lymphocyte survival and function, making it a promising treatment option for autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib. [2023]

A 62-year-old woman with psoriasis experienced a flare-up of her condition after starting treatment with imatinib for a metastatic gastrointestinal stromal tumor, indicating a potential adverse effect of the medication on pre-existing skin conditions.

The psoriasis improved after stopping imatinib and recurred upon resuming treatment, but it was effectively managed with a combination of imatinib and low-dose methotrexate, suggesting a possible strategy for patients with similar issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of imatinib-related exacerbation of psoriasis in a patient with a gastrointestinal stromal tumour. Cheng, H., Geist, DE., Piperdi, M., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4206614/

Regorafenib in gastrointestinal stromal tumors: clinical ... Regorafenib, an orally available multitargeted tyrosine kinase inhibitor with antiangiogenic activity, has also demonstrated preclinical evidence of activity.

2. gisttrials.org gisttrials.org/iLRG/details.php?Trial=283

trial detail - GIST clinical trials Regorafenib Effective for Gastrointestinal Stromal Tumor When Other Treatments Stop Working · IJC Dec. 2010: REGORAFENIB (BAY 73-4506): A NEW ORAL MULTIKINASE ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5573380/

Treatment patterns, efficacy and toxicity of regorafenib in ... Regorafenib was approved as third-line therapy for advanced Gastrointestinal Stromal Tumour (GIST) at a starting dose of 160 mg daily 3 weeks on, 1 week off.

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140673612618571/abstract

Efficacy and safety of regorafenib for advanced ... Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2011.39.9394

Efficacy and Safety of Regorafenib in Patients With ... Metastatic GI stromal tumor (GIST) is a life-threatening disease with no therapy of proven efficacy after failure of imatinib and sunitinib.

6. stivarga.com stivarga.com/gist/safety

Safety Data in Gastrointestinal Stromal Tumor Monitor AEs frequently during the first 8 weeks1. STIVARGA® (regorafenib) treatment-emergent AEs most frequently occur early and do not increase over time1.

7. clinicalsarcomaresearch.biomedcentral.com clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/s13569-019-0123-4

Toxicity management of regorafenib in patients with gastro ... Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02439723

Study Details | NCT02439723 | Effects of LBM and PPIs on ... The FDA and Health Canada have approved regorafenib at a daily dose of 160mg for the treatment of metastatic colorectal cancer and gastrointestinal stromal ...

9. gisttrials.org gisttrials.org/iLRG/drug_detail.php?drug=54

Drug Details - GIST clinical trials Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable GI Stromal Tumor After Failure of Imatinib and Sunitinib: A Multicenter Phase ...