Chiauranib for Advanced Solid Malignant Tumors and Relapsed/Refractory SCLC.

NCT05271292 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CAR107
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 11

Brief Summary

This is a Phase 1b/2, single-arm, open-label, dose-escalation study including 2 stages: Phase 1b: Dose-Escalation Stage (Single-Dose and Consecutive-Dose Periods) Phase 2: recommended Phase 2 dose (RP2D) of chiauranib will be given to all patients enrolled in this phase once daily for 28-day cycles continuously with no interruption between cycles.

Conditions

Small Cell Lung Cancer; Advanced Solid Malignant Tumor

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs) and other safety parameters

  Number of patients experienced AEs

  Until 30 days after a patient takes the last dose of the study drug

• Incidence and characteristics of DLTs

  Number of patients experienced any dose limited toxicity

  34 days

• MTD and recommended Phase 2 dose (RP2D)

  Determination of recommended phase II dose

  34 days

Secondary Outcomes (15)

• Time to maximum concentration (Tmax)

  Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)

• Maximum plasma concentration (Cmax)

  Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)

• Area under the plasma concentration-time curve from 0 to infinity (AUC 0-inf)

  Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)

• Half-life (t½)

  Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)

• Trough plasma concentration (Cmin)

  Phase 1b: days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles. Phase 2: days 1, 14, 28 during Cycle 1; and day 28 in Cycle 2 and all subsequent cycles (all cycles in phase 1b and 2 are 28 days each)

Study Arms (3)

Study arm (35 mg)

EXPERIMENTAL

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

Drug: Chiauranib

Study arm (50 mg)

EXPERIMENTAL

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

Drug: Chiauranib

Study arm (65 mg)

EXPERIMENTAL

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

Drug: Chiauranib

Interventions

Chiauranib DRUG

Phase 1b: Each patient will undergo both a single-dose period (6 days) and a consecutive-dose (1 cycle of 28 days) period Phase 2: Patients will take the RP2D once daily for 28-day cycles continuously with no interruption between cycles

Also known as: CS2164

Study arm (35 mg); Study arm (50 mg); Study arm (65 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is at least 18 years of age, regardless of gender. Patient has a diagnosis of histologically or cytologically confirmed advanced solid malignant tumor (including SCLC, NSCLC, colorectal carcinoma, pancreatic carcinoma, hepatocellular carcinoma, ovarian cancer, neuroendocrine tumors, non-Hodgkin's lymphoma, and others) that has relapsed from or is refractory to standard therapy or for which no standard therapy exists.
• Patient has at least one measurable target lesion as defined by RECIST1.1, i.e., a lesion that has radiologic evidence of disease progression, after treatment with radiotherapy or local-regional therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at enrollment.
• Major organ functions meet the following criteria (no corrective treatment, such as G CSF, erythropoietin, and blood transfusion, within 2 weeks before enrollment):
• Hematology: absolute neutrophil count (ANC) ≥1.5×109/L, platelet ≥100×109/L, hemoglobin ≥100 g/L.
• Biochemistry: total bilirubin ≤1.25×upper limit of normal (ULN), both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×ULN (≤5×ULN for patients with hepatic metastasis), creatinine clearance \>60 mL/min (according to Cockcroft-Gault equation), fasting triglyceride ≤3.0 mmol/L, fasting total cholesterol ≤7.75 mmol/L.
• Coagulation panel: international normalized ratio (INR) \<1.5.
• Patient has a life expectancy ≥3 months.
• Patient is able to provide voluntary informed consent.
• Women of childbearing potential (WOCBP) must be willing and able to take highly effective contraceptive measures during the entire study treatment period and for 12 weeks after the last dose of study drug (see Appendix 11.7). Women of childbearing potential include premenopausal and not sterilized (by hysterectomy, bilateral ligation of fallopian tubes, or bilateral oophorectomy) females who have passed menarche.
• Male patients must be willing and able to use male condoms and their female partners who are WOCBP during the entire study treatment and for the 12 weeks after the last dose of the study drug.

You may not qualify if:

• Patient has received any systemic anticancer therapy (including chemotherapy, targeted therapy, biological immunotherapy, any investigational drug, or anti-cancer herbal medicine) within 21 days before enrollment, or any blood support therapy (including blood transfusion, blood products, or hematopoiesis stimulating agents such as granulocyte-colony stimulating factor \[G-CSF\]) within 2 weeks before enrollment.
• a. Patients who are receiving corticosteroids at a dose of \> 10 mg prednisone or equivalent of other systemic steroids will be excluded.
• Patient with prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of investigational regimen.
• Patient has uncontrolled or significant cardiovascular diseases, including:
• New York Heart Association (NYHA) grade II or higher congestive cardiac failure, unstable angina pectoris, and/or myocardial infarction within the 6 months prior to the first dose of the investigational drug, clinically significant arrhythmia unable to be controlled with medical treatment or left ventricular ejection fraction (LVEF) \< 50% at screening.
• Primary cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy).
• Clinically significant history of prolonged QTc interval, or QTcF interval \>470ms for females or \>450 ms for males during screening.
• Coronary heart disease with symptoms requiring medication.
• Patient has hypertension at screening (defined as systolic blood pressure \[SBP\] ≥140 mmHg, diastolic blood pressure \[DBP\] ≥90 mmHg). (Patients with a known history of hypertension if blood pressure is considered well controlled on a single anti-hypertensive medication (systolic blood pressure \<140 mmHg and diastolic blood pressure \<90 mmHg at screening) and in whom there has been no change in blood pressure medication for 3 months prior to screening due to poor control.)
• Patient has active hemoptysis, has had active bleeding within 6 months prior to enrollment, or has definite predisposition to gastrointestinal bleeding as determined by the investigator (e.g., esophageal varix associated with bleeding risk, local active ulcer lesions).
• Patient has uncontrolled pleural effusion, hydropericardium, or ascites.
• Patient has active or symptomatic central nervous system (CNS) metastases that require treatment.
• Patient has a history of deep vein thrombosis, pulmonary embolism, or other serious thrombotic event within 6 months prior to enrollment.
• Patient has an interstitial lung disease (ILD) that requires treatment, such as idiopathic interstitial pneumonia, pulmonary fibrosis, or evidence of ILD in baseline chest computed tomography (CT) or magnetic resonance imaging (MRI).
• Patient has any current toxicity (except alopecia) of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, Grade 2 or higher caused by previous therapy.

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (11)

California Cancer Associates-Encintas

Encinitas, California, 92024, United States

RECRUITING

Providence/St. Joe Cancer Institute/Crosson Cancer Institute

Fullerton, California, 92835, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Dana Farber Cancer Institue

Boston, Massachusetts, 02215, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89119, United States

RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

RECRUITING

OU Health

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Sarah Cannon Research Center

Nashville, Tennessee, 37203, United States

RECRUITING

North Houston Cancer Clinics

Huntsville, Texas, 77340, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (1)

• van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011 Nov 12;378(9804):1741-55. doi: 10.1016/S0140-6736(11)60165-7. Epub 2011 May 10.

  PMID: 21565397 RESULT

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

chiauranib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Cabilia Pichardo, MD

  Executive Director of Clinical Development

  STUDY DIRECTOR

Central Study Contacts

Zhijian Li, MD

CONTACT

732-584-6269; zhijian_li@chipscreen.com

Liz Wieland

CONTACT

Elizabeth_Wieland@chipscreen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be enrolled sequentially in 3 dose-escalating cohorts (Chiauranib capsules 35mg, 50 mg and 65 mg once daily)

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: March 9, 2022
• Study Start: August 26, 2022
• Primary Completion: March 1, 2025
• Study Completion: May 1, 2025
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)