Rogaratinib for Sarcoma and Gastrointestinal Stromal Tumors

Recruiting at 18 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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

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 receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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.

How is the drug Rogaratinib different from other treatments for gastrointestinal stromal tumors?

Rogaratinib is unique because it targets fibroblast growth factor receptors (FGFRs), which is different from other treatments like imatinib, sunitinib, and regorafenib that primarily target KIT and PDGFRα mutations. This different mechanism of action may offer a new approach for patients who have developed resistance to existing therapies. ^{1 2 3 4 5}

Research Team

Suzanne George

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Discovery and pharmacological characterization of AZD3229, a potent KIT/PDGFRα inhibitor for treatment of gastrointestinal stromal tumors. [2021]

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

Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. [2021]

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Beyond standard therapy: drugs under investigation for the treatment of gastrointestinal stromal tumor. [2018]

5. Japan 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. [2022]