Rogaratinib for Sarcoma and Gastrointestinal Stromal Tumors

Not currently recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 drugs, QT prolonging

Disqualifiers: Pregnancy, Uncontrolled illness, Allergies, 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

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the effectiveness of the drug rogaratinib for patients with sarcoma or a gastrointestinal stromal tumor (GIST) lacking a specific enzyme (SDH-deficient). The researchers aim to determine if rogaratinib can halt tumor growth by blocking proteins involved in cell growth. Individuals with sarcoma who have changes in fibroblast growth factor receptors (FGFRs) or those with SDH-deficient GIST who have not responded to chemotherapy may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention avoiding certain drugs that interact with rogaratinib. You should discuss your current medications with the study team to ensure there are no interactions.

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

Research shows that rogaratinib is being tested for safety and effectiveness in treating certain cancers, such as sarcoma and gastrointestinal stromal tumors (GIST). Earlier studies found that most patients tolerate rogaratinib well. Common side effects include fatigue, nausea, and diarrhea, but these are usually mild to moderate.

Since this trial is in phase 2, the drug has already been shown to be safe in humans. Previous studies have not identified any serious or unexpected side effects that would cause major concern. Rogaratinib works by blocking certain proteins that help cancer cells grow. This targeted approach might reduce the risk of serious side effects compared to some other cancer treatments.

Overall, while no treatment is completely without risk, current evidence suggests that rogaratinib is relatively safe for further testing in this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sarcoma and gastrointestinal stromal tumors, which often involve surgery, radiation, and chemotherapy, rogaratinib offers a new approach by targeting the fibroblast growth factor receptor (FGFR). This is a unique mechanism of action that could provide a more tailored treatment option. Researchers are excited because rogaratinib might offer increased effectiveness with potentially fewer side effects, making it a promising alternative to existing therapies.

What evidence suggests that rogaratinib might be an effective treatment for sarcoma and gastrointestinal stromal tumors?

Research has shown that rogaratinib might help treat certain types of sarcoma and gastrointestinal stromal tumors (GIST). It blocks proteins called fibroblast growth factor receptors (FGFRs), which aid tumor growth. By blocking these proteins, rogaratinib could slow or stop tumor growth. Early results suggest that rogaratinib can shrink tumors with specific FGFR changes. Although information on its effectiveness in people remains limited, its mechanism offers hope for patients with FGFR-related tumors. The drug aims to provide a new option for those with few effective treatments. Participants in this trial will receive rogaratinib as the sole treatment. ^{1 5 6 7 8}

Who Is on the Research Team?

Suzanne George

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with advanced sarcoma showing FGFR alterations or SDH-deficient GIST, not suitable for surgery. Must have measurable disease, acceptable organ function, and be willing to undergo a biopsy if safe. Excludes those with certain viral infections unless treated, pregnant women, and individuals on medications that interact with Rogaratinib.

Inclusion Criteria

Participant is willing to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Absolute neutrophil count >= 1,000/mcL

Platelets >= 100,000/mcL

Exclusion Criteria

Patients with uncontrolled intercurrent illness

You are not currently taking any experimental drugs or treatments.

I am not taking any medications that affect my heart's electrical cycle.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rogaratinib orally twice daily on days 1-28 of each cycle, repeating every 28 days for up to 24 cycles

24 months

Biopsies at baseline and progression, CT, MRI, and PET-CT throughout the study

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person) at 30 days post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Rogaratinib

Trial Overview The trial is testing Rogaratinib's effectiveness in halting tumor growth by blocking enzymes needed for cell growth in patients with specific protein changes in their sarcomas or who have a particular type of GIST.

How Is the Trial Designed?

Group I: Treatment (rogaratinib) Experimental Treatment 6 Interventions

Patients receive rogaratinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and CT, MRI, and PET-CT throughout the study. Patients may also undergo blood sample collection on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

In a subgroup analysis of 17 Japanese patients with advanced gastrointestinal stromal tumors (GIST), regorafenib significantly improved progression-free survival (PFS) compared to placebo, with a hazard ratio of 0.08, indicating a strong treatment effect.

Regorafenib was associated with a manageable safety profile, although treatment-related adverse events, particularly hand-foot skin reaction, were more common in regorafenib-treated patients (92%) compared to those on placebo (20%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial. Komatsu, Y., Doi, T., Sawaki, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04595747

NCT04595747 | Testing the Anti-cancer Drug, Rogaratinib ... This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor ...

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=000475-C&&query=0

NIH Clinical Center: Search the Studies Researchers want to see if a new drug can help treat sarcomas. Objective: To test if rogaratinib will shrink tumors in patients with a sarcoma that has ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6774913/

Outcome of 1000 patients with gastrointestinal stromal tumor ... Median survival was 57 months, compared to 19 months historically. Adjuvant imatinib was then tested in randomized clinical trials. After resection of primary ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822397

Incidence and Survival Outcomes of Gastrointestinal ... In this study, we evaluated recent GIST incidence trends and survival outcomes by race and ethnicity using data from the National Cancer ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473224

Navigating Ongoing Challenges in GI Stromal Tumors Adjuvant imatinib durations longer than 3 years might improve survival further compared with the 3-year duration, as suggested by some analyses ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-08011

Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), ... This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor ...

7. dana-farber.org dana-farber.org/clinical-trials/21-070

Phase 2 Study of Rogaratinib (BAY 1163877) in the ... This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2666831/

Gastrointestinal Stromal Tumors (GIST) and Their ... There are no data to indicate that imatinib increases the cure rate of patients with resection of primary disease. The first study examining adjuvant imatinib ...