- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05731518
SC0245 and Irinotecan in Treating Patients With Relapsed Extensive-Stage Small Cell Lung Cancer (ES-SCLC)
A Phase Ib/II , Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Effects of SC0245 in Combination With Irinotecan in Patients With ES-SCLC
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study will have three parts, phase 1 dose escalation (Part 1), phase 1 dose expansion (Part 2), and phase 2 combination therapy (Part 3).
Subjects will receive SC0245 and Irinotecan combination therapy. The study is composed of 67 subjects.
Irinotecan 80mg/m2 via IV administered for every 4 weeks (fixed dosing) in Day 1 Day8 and Day 15 of each cycle, and SC0245 administered with a 3-day on and 4-day off schedule in Day 1 Day8 and Day 15 of each cycle. One cycle is consisted of 28 days.
Study treatment will be continued until objective disease progression (unless other criteria for treatment discontinuation are met). Tumor evaluation using CT or MRI by RECIST 1.1 every 8weeks(±1week) until objective disease progression. RECIST 1.1 scans will be analyzed by the investigator on site. If a subject discontinues study treatment prior to disease progression, they should continue to be assessed using RECIST 1.1 until disease progression and then followed up for survival.
Primary Objective:
Part 1 (phase 1 dose escalation): To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SC0245 in combination with irinotecan in patients with advanced solid tumors.
Part 2 (phase 1 dose expansion): To evaluate the safety and tolerability of SC0245 in combination with irinotecan in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC).
Part 3(phase 2 combination therapy): To evaluate the preliminary anti-tumor activity of SC0245 in combination with irinotecan in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC).
Secondary Objective:
Part 1 (phase 1 dose escalation): To characterize the PK profile and the preliminary anti-tumor activity.
Part 2 (phase 1 dose expansion): To characterize the PK profile, safety and tolerability and the preliminary anti-tumor activity in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC).
Part 3(phase 2 combination therapy): To characterize the safety and tolerability and the preliminary anti-tumor activity in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC).
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: SHUN LU, Prof
- Phone Number: 13601813062
- Email: Shun_lu@hotmail.com
Study Contact Backup
- Name: YONGFENG YU, Chief
- Phone Number: 18017321559
- Email: yuyongfeng212@126.com
Study Locations
-
-
Shanghai
-
Shanghai, Shanghai, China, 200030
- Recruiting
- Shanghai Chest Hospital
-
Contact:
- SHUN LU, Prof
- Phone Number: 13601813062
- Email: Shun_lu@hotmail.com
-
Contact:
- YONGFENG YU, Chief
- Phone Number: 18017321559
- Email: yuyongfeng212@126.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumor.
Phase 1b dose-escalation stage: patients with advanced solid tumors, who have received standard treatment, for who no standard treatment exists, who are not suitable for standard treatment at the current situation, or who could not tolerate standard treatment.
Phase 1b dose-expansion stage and phase 2: patients with ES-SCLC who have received first-line platinum-based regimen chemotherapy with or without immunotherapy or intolerance to such therapy.
- Measurable lesions according to RECIST version 1.1 (only applicable for phase 1b dose-expansion and Phase 2).
- Male or non-pregnant, non-lactating female patients age ≥18 years on day of signing the informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
- Life expectancy ≥ 3 months.
- Adequate organ function .
- Females of child-bearing potential (nonlactating) must have a negative blood pregnancy test within 7 days before enrollment, and must agree to use a medically effective contraception from the time they provided the informed consent until at least 6 months (or at least 180 days) after the last dose of study drug, unless surgical sterilization or menopause for more than 1 year. Patients who are sexually active men with a female partner of child-bearing potential must agree to use adequate contraception from the time they provided informed consent until at least 6 months after the last dose.
- Subjects voluntarily participate in this study and sign the informed consent form.
Exclusion Criteria:
- Received chemotherapy within 3 weeks before first dose of study drug (6 weeks for nitrosoureas or mitomycin C)
- Received wide field radiotherapy within 4 weeks before first dose of study drug (previous palliative radiation therapy for metastatic disease is permitted if it has been completed at least 1 week before first dose of study drug and related toxicity has recovered to ≤ grade 1)
- Received any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugates (ADC) within 5 half-lives or 4 weeks (whichever is shorter) before first dose.
- Received any other type of anti-tumor therapy including other investigational drugs or treatments not listed above within 4 weeks before first dose of study drug.
- Had major organ surgery, except diagnostic biopsy, or significant trauma within 4 weeks, or not fully recovered from surgery within 4 weeks before first dose of study drug.
- Received traditional Chinese herbal medicines with anti-tumor indications within 2 weeks before first dose of study drug.
- Previously received any Ataxia-Telangiectasia and Rad3 Related(ATR)inhibitor.
- Continuous toxicities due to prior treatments that do not recover to ≤ Grade 1 severity per NCI CTCAE v5.0 except for clinically non-significant events judged by the Investigator (e.g., alopecia, grade 2 peripheral neurotoxicity, stable hypothyroidism with hormone replacement therapy, etc.)
- Allergy to any component of the SC0245 tablets and irinotecan injection or who meet contraindications to irinotecan. In addition, the prohibited concomitant drugs in irinotecan label should be avoided.
- Crigler-Najjar syndrome (Type I and II) or UGT1A1 mutation that increases irinotecan toxicity (Gilbert's syndrome).
Central nervous system (CNS) metastases meeting any of the following condition:
- Presence of new or progressive lesions in brain by imaging within 4 weeks prior to first dose of study drug
- Presence of symptoms of CNS metastasis
- Received corticosteroids, radiotherapy, or dehydration drugs within 1 week to control symptoms of CNS metastasis (except for patients who completed radiotherapy for brain metastases, no use of cortisol and dehydration drugs without neurologic symptoms for more than 1 week, and brain metastases are in a stable state or have shrinkage during follow-up visit at least 2 weeks later, which need to be confirmed before first dose of study drug)
- Carcinomatous meningitis
- Brain stem (midbrain, pons, medulla oblongata) and spinal cord metastases
- Active infections that require systematic treatment
Severe cardiovascular disorder, who meet any of the following conditions:
- corrected QT interval(QTc)> 470 ms
- Severe cardiac rhythm or conduction abnormalities, including but not limited to complete left bundle branch block, atrioventricular block of degree II or above, rapid ventricular tachycardia (including frequent premature ventricular contractions), torsades de pointes.
- Any risk factors that increase the prolongation of the QTc interval, such as uncorrectable hypokalemia, genetic long QT syndrome, taking medications that prolong the QTc interval (mainly antiarrhythmic drugs of Class Ia, Ic, or III)
- Congestive heart failure (New York Heart Association Class≥3), or a left ventricular ejection fraction of less than 50%
- Clinically uncontrolled hypertension, defined as systolic blood pressure (SBP) ≥ 160 mmHg and diastolic blood pressure (DBP) ≥ 100 mmHg after medication.
- Acute coronary syndrome, aortic dissection, myocardial infarction, unstable angina pectoris, cerebrovascular accident, or other Grade 3 or higher cardiovascular or cerebrovascular event within 6 months prior to the first dose
- Major gastrointestinal surgery, or malabsorption syndrome, or are unable to swallow tablets that may impair the absorption of SC0245 tablets, or other active diseases or pathological conditions that may impact absorption, distribution, metabolism, excretion of SC0245 (such as uncontrollable nausea, vomiting, diarrhea, intestinal obstruction) as judged by the Investigator within 4 weeks before first dose of study drug.
- Tertiary-interstitial effusion (e.g., pericardial, pleural, and peritoneal effusion) requiring repeated drainage or other treatments, but still could not be controlled within two weeks before first dose of study drug and are judged unsuitable to participate in the study by the Investigator.
- Patients with other known malignant diseases. Exceptions: History of curative treatment for malignancy with no recurrence within 5 years; adequately treated non-melanoma skin cancer or lentigo malign; carcinoma in situ adequately treated with no signs of recurrence
- UGT1A1 mutation.
- Patients with underlying medical conditions (including laboratory abnormalities), alcohol or drug abuse or dependence that may affect study drug administration or the interpretation of drug toxicity or adverse events (AEs), or result in poor compliance, and are judged unsuitable to participate in the study by the Investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SC0245 and irinotecan combination
SC0245 and irinotecan combination are administered one cycle that is consisted of 28 days until disease progression or death or loss of follow-up or withdrawal.
|
SC0245 Quaque Die(QD) administered with a 3-day on and 4-day off schedule in Day 1 Day8 and Day 15 of each cycle.
One cycle is consisted of 28 days.
Other Names:
Irinotecan 80mg/m^2 via IV administered for every 4 weeks (fixed dosing) in Day 1 Day8 and Day 15 of each cycle.
One cycle is consisted of 28 days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 1 (phase 1 dose escalation):Maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of SC0245 and irinotecan
Time Frame: Up to 28 days
|
MTD Will be defined as the highest dose level at which =< 30% patients experience dose limiting toxicity.
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optional therapeutic intervention, meets protocol-defined criteria.
The RP2D will be determined based on MTD and the feasibility of the administration.
|
Up to 28 days
|
Part 2 (phase 1 dose expansion):Safety and tolerability in terms of adverse events
Time Frame: From the first dose of study treatment until 30 days after the last dose, up to approximately 24 months
|
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters.
|
From the first dose of study treatment until 30 days after the last dose, up to approximately 24 months
|
Part 3(phase 2 combination therapy):Objective response rate (ORR)
Time Frame: Up to 24 months.
|
Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1.
|
Up to 24 months.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control Rate (DCR) Based on RECIST v1.1
Time Frame: Assessed every 8 weeks, up to 24 months.
|
Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1.
|
Assessed every 8 weeks, up to 24 months.
|
Duration of Response (DoR) Based on RECIST v1.1
Time Frame: Assessed every 8 weeks, up to 24 months.
|
Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.
|
Assessed every 8 weeks, up to 24 months.
|
Progression-free Survival (PFS) Based on RECIST v1.1
Time Frame: Assessed every 8 weeks, up to 24 months.
|
Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
|
Assessed every 8 weeks, up to 24 months.
|
Overall Survival (OS)
Time Frame: At 1 year and 2 years.
|
Defined as the time from the start of combination therapy until death due to any cause.
|
At 1 year and 2 years.
|
Incidence of adverse events of SC0245 and irinotecan
Time Frame: From the first dose of study treatment until 30 days after the last dose, up to approximately 24 months
|
Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
A toxicity will be considered to be an adverse event that is possibly, probably or definitely related to treatment.
The maximum grade of toxicity for each category of interest will be recorded for each patient, and the summary results will be tabulated by category, grade, and dose level.
Serious (>= grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.
|
From the first dose of study treatment until 30 days after the last dose, up to approximately 24 months
|
Maximum observed blood concentration (Cmax) of SC0245
Time Frame: Pre-dose up to approximately 6 months
|
Defined as assessments for measuring maximum blood concentration of SC0245
|
Pre-dose up to approximately 6 months
|
AUC Area under the Plasma Concentration versus Time Curve (AUC) of SC0245
Time Frame: Pre-dose up to approximately 6 months
|
Defined as assessments for evaluating the Area Under the Concentration-Time Curve (AUC)
|
Pre-dose up to approximately 6 months
|
Elimination half-life (t1/2) of SC0245
Time Frame: Pre-dose up to approximately 6 months
|
Defined as the time required for half of the drug SC0245 to be eliminated from the blood.
|
Pre-dose up to approximately 6 months
|
Collaborators and Investigators
Investigators
- Study Chair: SHUN LU, Prof, Shanghai Chest Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Small Cell Lung Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
Other Study ID Numbers
- SC0245-102
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Small Cell Lung Cancer
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung CancerUnited States
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
Washington University School of MedicineMerck Sharp & Dohme LLCWithdrawnNSCLC | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Small Cell Lung Extensive Stage
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedTobacco Use Disorder | Stage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Limited Stage Small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB...United States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
Peking Union Medical College HospitalRecruitingNon Small Cell Lung Cancer Stage III | Small-Cell Lung CancerChina
-
University of Maryland, BaltimoreUniversity of Maryland, College ParkTerminatedNon-Small Cell Lung Cancer, Small Cell Lung Cancer | Platinum Responsive MalignanciesUnited States