Gastrointestinal Stromal Tumors
Conditions
Keywords
Gastrointestinal Stromal Tumors,GIST,DCC-2618,Ripretinib
Brief summary
The primary objective of this trial is to evaluate the progress free survival (PFS) of DCC-2618 in patients with advanced gastrointestinal stromal tumors who have progressed with prior anticancer therapies based on independent radiologic review.
Detailed description
The primary objective of this trial is to evaluate the progress free survival (PFS) of DCC-2618 in patients with advanced gastrointestinal stromal tumors who have progressed with prior anticancer therapies based on independent radiologic review. This study enrolled 39 subjects of 9 sites in China mainland, and all enrolled subjects received DCC-2618 after enrollment as treatment. The study used EDC to collect patient data and IRT system for patient randomization, using Imaging Endpoints as the central image to evaluate the PFS.
Interventions
DRUGDCC-2618
Oral kinase inhibitor
Sponsors
Zai Lab (Shanghai) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥18 years of age. * Patients with advanced gastrointestinal stromal tumors. * Subjects who have progressed or documented intolerance after previous treatments. * Sign informed consent, understand the Protocol and could follow the Protocol. * The subject had at least one measurable lesion. * Adequate organ function and bone marrow reserve
Exclusion criteria
* Treatment with anticancer therapy, including investigational therapy, or investigational procedures within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of investigational drug. * Prior treatment with DCC-2618. * Previously or currently has an additional malignancy that is progressing or required active treatment, which may interfere with the safety or efficacy evaluation of DCC-2618. * Patient has known active central nervous system metastases. * New York Heart Association class II - IV heart disease, active ischemia or any other uncontrolled cardiac condition. * Arterial thrombotic or embolic events within 6 months before the first dose of investigational drug. * Venous thrombotic events within 3 months before the first dose of investigational drug. * 12-lead electrocardiogram (ECG) demonstrating QT interval corrected by Fridericia's formula \>450 ms in males or \>470 ms in females at screening or history of long QT interval syndrome. * Left ventricular ejection fraction (LVEF) \<50% at screening. * Use of known substrates or inhibitors of breast cancer resistance protein (BCRP) transporters within 14 days or 5 x the half-life (whichever is longer) prior to the first dose of investigational drug. * Major surgeries within 4 weeks of the first dose of investigational drug. * Any other clinically significant comorbidities, which in the judgment of the investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks. * Active viral infections. * If female, the patient is pregnant or lactating, or plans to become pregnant during the study treatment period. * Known allergy or hypersensitivity to any component of the investigational drug. * Gastrointestinal abnormalities. * Any active hemorrhages, excluding hemorrhoids or gum bleeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Approximately 10 months since the first subject enrolled. | Progression-Free Survival (PFS) is defined as the time from the first dose of study drug to the first occurrence of disease progression based on independent radiology review or death due to any cause (whichever occurred first). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Approximately 15 months since the first subject enrolled. | The objective response rate (ORR) is defined as the percentage of participants who achieved confirmed complete response (CR) or partial responses (PR) based on independent radiology review. |
| Overall Survival (OS) | Approximately 28 months since the first subject enrolled. | Overall survival (OS) is defined as the time from the first dose of study drug to all-cause death. |
| Time to Best Response (TBR) | Approximately 15 months since the first subject enrolled. | Time to Best Response(TBR) based on independent radiology review is defined as the duration from the date of the first dose of the investigational drug to the date of confirming the best response. |
| Disease Control Rate (DCR) (Confirmed CR + Confirmed PR + SD) for 12 Weeks | Approximately 15 months since the first subject enrolled. | Disease control rate (DCR) based on independent radiology review (confirmed CR + confirmed PR + SD for 12 weeks) |
Countries
China
Participant flow
Recruitment details
Between April 2020 and August 2020, 39 patients were enrolled, and all received at least one dose of study drug.
Pre-assignment details
50 patients were assessed for eligibility, 11 experienced screen failure.
Participants by arm
| Arm | Count |
|---|---|
| DCC-2618 DCC-2618 drug is 50mg per tablet, 150mg once a day, with 28 days as a treatment cycle.
DCC-2618: Oral kinase inhibitor | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Remained on treatment | 6 |
| Overall Study | Survival follow-up | 11 |
| Overall Study | Withdrawal of informed consent | 1 |
Baseline characteristics
| Characteristic | DCC-2618 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 55.1 years |
| ECOG performance status 0 | 7 Participants |
| ECOG performance status 1 | 28 Participants |
| ECOG performance status 2 | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 39 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 39 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 20 / 39 |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 10 / 39 |
Outcome results
Primary
Progression-Free Survival (PFS)
Progression-Free Survival (PFS) is defined as the time from the first dose of study drug to the first occurrence of disease progression based on independent radiology review or death due to any cause (whichever occurred first).
Time frame: Approximately 10 months since the first subject enrolled.
Population: Efficacy analyses were performed using the efficacy analysis set (EAS), consisting of the 38 participants who had received continuous ripretinib treatment since C1D1. 1 subject discontinued treatment due to clinical progression during the intensive blood sampling period and a total of 38 subjects who entered treatment period (continuous dose period) were included in the Efficacy Analysis Set (EAS).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCC-2618 | Progression-Free Survival (PFS) | 6.44 months |
Secondary
Disease Control Rate (DCR) (Confirmed CR + Confirmed PR + SD) for 12 Weeks
Disease control rate (DCR) based on independent radiology review (confirmed CR + confirmed PR + SD for 12 weeks)
Time frame: Approximately 15 months since the first subject enrolled.
Population: 1 subject discontinued treatment due to clinical progression during the intensive blood sampling period and a total of 38 subjects who entered treatment period (continuous dose period) were included in the Efficacy Analysis Set (EAS).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DCC-2618 | Disease Control Rate (DCR) (Confirmed CR + Confirmed PR + SD) for 12 Weeks | 20 Participants |
Secondary
Objective Response Rate (ORR)
The objective response rate (ORR) is defined as the percentage of participants who achieved confirmed complete response (CR) or partial responses (PR) based on independent radiology review.
Time frame: Approximately 15 months since the first subject enrolled.
Population: 1 subject discontinued treatment due to clinical progression during the intensive blood sampling period and a total of 38 subjects who entered treatment period (continuous dose period) were included in the Efficacy Analysis Set (EAS).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DCC-2618 | Objective Response Rate (ORR) | 8 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) is defined as the time from the first dose of study drug to all-cause death.
Time frame: Approximately 28 months since the first subject enrolled.
Population: 1 subject discontinued treatment due to clinical progression during the intensive blood sampling period and a total of 38 subjects who entered treatment period (continuous dose period) were included in the Efficacy Analysis Set (EAS).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCC-2618 | Overall Survival (OS) | 25.56 months |
Secondary
Time to Best Response (TBR)
Time to Best Response(TBR) based on independent radiology review is defined as the duration from the date of the first dose of the investigational drug to the date of confirming the best response.
Time frame: Approximately 15 months since the first subject enrolled.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DCC-2618 | Time to Best Response (TBR) | 2.25 months |