Small Cell Lung Cancer, Extensive-stage Small Cell Lung Cancer
Conditions
Brief summary
This is a phase II, open-label, single arm, single-stage study. Both, chemo-sensitive and chemo-resistant patients will be enrolled and treated with 4 cycles of combination of Guadecitabine and carboplatin
Interventions
DRUGGuadecitabine
Guadecitabine 30 mg/m2 subcutaneously Days 1-5
DRUGCarboplatin
Carboplatin AUC 4 IV Day 5
Sponsors
Astex Pharmaceuticals, Inc.
Indiana University School of Medicine
Shadia Jalal, MD
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 subjects, age ≥ 18 years. * Histological or cytological diagnosis of small cell lung cancer. Subjects must have extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or pericardial effusion or hematogenous metastases. * Patient should not have received more than 1 prior line of chemotherapy (could have received immunotherapy which does not count as chemotherapy). * ECOG PS 0-1 * Measurable disease as per RECIST v1.1. Subjects may have bone-only disease. NOTE: Bone-only subjects are eligible if their disease can be documented/evaluated by bone scans, CT or MRI. Their disease will be assessed using MD Anderson criteria. NOTE: Previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation. * Adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1,500/mm3 * Platelet count ≥ 100,000/mm3 * Total bilirubin ≤ 1.5 x upper limit of normal (ULN). For subjects with Gilbert's Disease, total bilirubin ≤ 3 x ULN * ALT and AST ≤ 2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤ 5×ULN * International Normalized Ratio (INR) ≤1.5, if not therapeutically anticoagulated. Subjects who are being therapeutically anticoagulated may be included provided that the anticoagulation regimen is stable and closely monitored. * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2 as determined using the Cockcroft-Gault formula. * Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. * Male and female subjects of child- bearing potential must agree to use an effective method of birth control from the screening visit through 6 months after the last dose of study drug.
Exclusion criteria
* Platinum refractory disease defined as disease progression during first line platinum containing chemotherapy regimen. Progression following platinum based therapy is allowed. * Prior therapy with a hypomethylating agent. * Previously untreated (non-irradiated), symptomatic brain metastases. No prior treatment is required for non-symptomatic brain metastases. Previously treated symptomatic brain metastases are permitted. * Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol. * Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy. (Suppressive therapy for chronic infections allowed, for example: Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed. Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.) * Hypersensitivity to (IMP) or components of the study treatment regimen. * Treated with any investigational drug within 3 weeks of first dose of study treatment. * Pregnant or breastfeeding. * Second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Time of treatment start until the criteria for disease progression or death. Up to a maximum of 7 months. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | AEs had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 5 months | All adverse events (AEs) had been determined according to the NCI Common Terminology Criteria for (NCI CTCAE) V5. A summary of the total number of participants is provided. |
| Objective Response Rate (ORR) | Up to a maximum of 7 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1 |
| Disease Control Rate (DCR) | Up to a maximum of 7 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. DCR defined as CR + PR + Stable Disease (SD) \>=8 weeks per RECIST 1.1 |
| Overall Survival (OS) | Time of treatment start until death or date of last contact, up to a maximum of 16 months. | Overall survival is defined as the time from treatment start until death or date of last contact. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Guadecitabine and Carboplatin Each cycle = 28 days; Subjects receive 4 cycles
Guadecitabine: Guadecitabine 30 mg/m2 subcutaneously Days 1-5
Carboplatin: Carboplatin AUC 4 IV Day 5 | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Guadecitabine and Carboplatin |
|---|---|
| Age, Continuous | 62.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 24 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 10 Participants |
| Smoking Status Current | 10 Participants |
| Smoking Status Former | 13 Participants |
| Smoking Status Never | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 24 |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 6 / 24 |
Outcome results
Primary
Progression Free Survival (PFS)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
Time frame: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 7 months.
Population: Out of 24 subjects, 15 subjects were in Platinum Sensitive group and 9 subjects were in Platinum Resistant group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Guadecitabine and Carboplatin (Platinum Sensitive) | Progression Free Survival (PFS) | 1.9 Months |
| Guadecitabine and Carboplatin (Platinum Resistant) | Progression Free Survival (PFS) | 1.7 Months |
Secondary
Adverse Events
All adverse events (AEs) had been determined according to the NCI Common Terminology Criteria for (NCI CTCAE) V5. A summary of the total number of participants is provided.
Time frame: AEs had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 5 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Guadecitabine and Carboplatin (Platinum Sensitive) | Adverse Events | 24 Participants |
Secondary
Disease Control Rate (DCR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. DCR defined as CR + PR + Stable Disease (SD) \>=8 weeks per RECIST 1.1
Time frame: Up to a maximum of 7 months
Population: Out of 24 subjects, 15 subjects were in Platinum Sensitive group and 9 subjects were in Platinum Resistant group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Guadecitabine and Carboplatin (Platinum Sensitive) | Disease Control Rate (DCR) | 42.9 Percentage of participants |
| Guadecitabine and Carboplatin (Platinum Resistant) | Disease Control Rate (DCR) | 33.3 Percentage of participants |
Secondary
Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1
Time frame: Up to a maximum of 7 months
Population: Out of 24 subjects, 15 subjects were in Platinum Sensitive group and 9 subjects were in Platinum Resistant group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Guadecitabine and Carboplatin (Platinum Sensitive) | Objective Response Rate (ORR) | 7.1 Percentage of participants |
| Guadecitabine and Carboplatin (Platinum Resistant) | Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from treatment start until death or date of last contact.
Time frame: Time of treatment start until death or date of last contact, up to a maximum of 16 months.
Population: Out of 24 subjects, 15 subjects were in Platinum Sensitive group and 9 subjects were in Platinum Resistant group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Guadecitabine and Carboplatin (Platinum Sensitive) | Overall Survival (OS) | 6.8 Months |
| Guadecitabine and Carboplatin (Platinum Resistant) | Overall Survival (OS) | 4.4 Months |