Chiauranib for Advanced Cancers

(SCLC Trial)

Recruiting in Palo Alto (17 mi)

+10 other locations

Overseen by Nashat Gabrail, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Chipscreen Biosciences, Ltd.

Must not be taking: Corticosteroids, Strong CYP3A4 inhibitors

Disqualifiers: Cardiovascular diseases, Hypertension, CNS metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called chiauranib for patients with advanced cancers that don't respond to standard treatments. It aims to block the signals that cancer cells need to grow. The focus is on patients with small cell lung cancer that has worsened after previous treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anticancer therapy at least 21 days before joining. If you are on strong CYP3A4 inhibitor or inducer drugs, you will need to stop those as well during the dose escalation stage. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What makes the drug Chiauranib unique for treating advanced cancers?

Chiauranib is unique because it is an oral drug that targets multiple pathways involved in cancer growth, including those related to blood vessel formation (angiogenesis), cell division (mitosis), and inflammation. This multi-target approach, particularly its inhibition of VEGFR2 and the ERK/STAT3 signaling pathway, makes it a promising option for cancers with no efficient treatment strategies, like transformed follicular lymphoma.

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Eligibility Criteria

This trial is for adults with advanced solid tumors or relapsed/refractory Small Cell Lung Cancer (SCLC) who have measurable disease progression. Participants must be in good physical condition (ECOG 0-1), have proper organ function, and a life expectancy that allows participation. Women of childbearing age and men must agree to use effective contraception during the study and for some time after.

Inclusion Criteria

Patient is able to provide voluntary informed consent

I have a tumor that can be measured and has grown after treatment.

I can and will use effective birth control during and for 12 weeks after the study.

Exclusion Criteria

I have a history of cancer.

I must continue taking certain medications during the study.

You currently have problems with using drugs or alcohol.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Participants undergo dose-escalation with chiauranib in 3 cohorts (35 mg, 50 mg, 65 mg) to determine the maximum tolerated dose and recommended Phase 2 dose.

34 days

Multiple visits for dose escalation and monitoring

Treatment

Participants receive the recommended Phase 2 dose of chiauranib once daily in 28-day cycles continuously with no interruption.

6 months

Visits on days 1, 14, 28 during Cycle 1; day 28 in Cycle 2 and all subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and survival outcomes.

30 days after last dose

Participant Groups

The trial is testing Chiauranib, an investigational drug, in two stages: Phase 1b determines the safe dosage through dose escalation, while Phase 2 administers this determined dose daily over continuous 28-day cycles without breaks to evaluate its effectiveness against cancer.

Group I: Study arm (65 mg) Experimental Treatment 1 Intervention

Phase 1b: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35, 50, and 65 mg, orally)

Group II: Study arm (50 mg) Experimental Treatment 1 Intervention

Phase 1b: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35, 50, and 65 mg, orally)

Group III: Study arm (35 mg) Experimental Treatment 1 Intervention

Phase 1b: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35, 50, and 65 mg, orally)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Karmanos Cancer Institute Detroit, MI

OU Health Oklahoma City, OK

Dana Farber Cancer Institue Boston, MA

Gabrail Cancer Center Research Canton, OH

More Trial Locations

Who Is Running the Clinical Trial?

Chipscreen Biosciences, Ltd. Lead Sponsor

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors. [2022] To evaluate safety and tolerability of cediranib, a highly potent and selective vascular endothelial growth factor signaling inhibitor, in Japanese patients with advanced solid tumors refractory to standard therapies.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway. [2023] Transformed follicular lymphoma (t-FL), for which there is no efficient treatment strategy, has a rapid progression, treatment resistance, and poor prognosis, which are the main reasons for FL treatment failure. In this study, we identified a promising therapeutic approach with chiauranib, a novel orally developed multitarget inhibitor targeting VEGFR/Aurora B/CSF-1R. We first determined the cytotoxicity of chiauranib in t-FL cell lines through CCK-8, EdU staining, flow cytometry, and transwell assays. We also determined the killing effect of chiauranib in a xenograft model. More importantly, we identified the underlying mechanism of chiauranib in t-FL tumorigenesis by immunofluorescence and Western blotting. Treatment with chiauranib significantly inhibited cell growth and migration, promoted apoptosis, induced cell cycle arrest in G2/M phase, and resulted in significant killing in vivo. Mechanistically, chiauranib suppresses the phosphorylation level of VEGFR2, which has an anti-t-FL effect by inhibiting the downstream MEK/ERK/STAT3 signaling cascade. In conclusion, chiauranib may be a potential therapy to treat t-FL, since it inhibits tumor growth and migration and induces apoptosis by altering the VEGFR2/ERK/STAT3 signaling pathway.

3. England pubmed.ncbi.nlm.nih.gov

A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours. [2018] This phase I study evaluated afatinib, an irreversible ErbB family blocker, plus paclitaxel in patients with advanced solid tumours likely to express human epidermal growth factor receptor (HER1/EGFR) or HER2.

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

Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. [2018] The efficacy of afatinib, an irreversible ErbB Family Blocker, was evaluated in patients who had 1 of 4 categories of solid tumors with epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) gene amplification or EGFR-activating mutations.

5. England pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of chiauranib, a novel angiogenic, mitotic, and chronic inflammation inhibitor, in patients with advanced solid tumors. [2020] Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα, and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF-1R. This phase I dose-escalation study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor activity of chiauranib in patients with refractory advanced solid tumor and lymphoma.