Stomach Neoplasms
Conditions
Brief summary
The study consisted of two parts. In Part 1 the study enrolled 38 patients (Step 1 Simon 2 step design) after which Step 2 was opened and the total enrollment target for the study (n=63) was exceeded due to a rapid enrollment (78 patients were entered). Part 2 of the study did not open due to the final overall insufficiency of efficacy observed in 78 patients. Sunitinib (SU011248) was administered orally daily for 4 weeks followed by a 2-week rest at a starting dose of 50 mg with provision for dose reduction based on tolerability. All patients received repeated cycles of sunitinib until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria were met. After discontinuation of treatment, patients were followed up in order to collect information on further antineoplastic therapy and survival.
Interventions
DRUGSunitinib
50mg daily, taken by mouth for 28 days followed by 2 weeks of drug free period was one cycle. Cycles were repeated until progression of disease or unacceptable toxicity was observed
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Gastric or gastroesophageal junction adenocarcinoma cyto/histologically documented * Disease progression/ recurrence after treatment with one prior single agent or combination chemotherapy regimen for advanced / metastatic disease (last dose at least 4 wks before study entry). Patients may have also received prior adjuvant therapy if recurrence occurred \> 6 months after adjuvant therapy completion * Evidence of measurable disease by radiographic technique * Adequate organ function.
Exclusion criteria
* Clinically relevant ascites (i.e. requiring paracentesis) * Severe weight loss * NCI CTCAE Grade 3 hemorrhage \<4 weeks of starting study treatment * Diagnosis of second malignancy within last 3 years * History of or known brain metastases, spinal cord compression, or carcinomatous meningitis * Known HIV * Serious acute or chronic illness * Current treatment on another clinical trial * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter | Number of patients with best overall response = complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response. CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
| Objective Response (Complete Response (CR) or Partial Response (PR)) | From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter | Number of patients with Objective Response (OR): confirmed CR or confirmed PR according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From start of study treatment until death | Time from the date of first dose of study medication to the date of death due to any cause. OS was calculated as (date of death minus the date of first dose date plus 1) divided by 7. |
| Progression-Free Survival | From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death | Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause. PFS was calculated as (first event date minus the date of first dose plus 1) divided by 7. |
| Duration of Response (CR or PR) | Day 28 of Cycle 1 and Day 28 of Cycles thereafter or death due to cancer | Time from the first documentation of confirmed objective response (CR or PR) to the first documentation of disease progression or to death due to any cause. CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
| Clinical Benefit Response (CBR)-Complete Response (CR), Partial Response (PR) or Stable Disease (SD) With Duration ≥ 24 Weeks | From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or clinical benefit response for at least 24 weeks on study | Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR or stable disease (SD) for at least 24 weeks on study according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. SD = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progessive disease (PD) taking as a reference the smallest sum of the longest dimensions since the treatment started. |
| Time to Tumor Progression (TTP) | From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter | Time from the start of study treatment to the first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose plus 1) divided by 7. |
Countries
China, Hong Kong, Italy, Japan, Portugal, South Korea, Taiwan
Participant flow
Pre-assignment details
This study used a Simon 2-stage design with objective response rate (ORR) as the primary efficacy endpoint. Enrollment was halted after Part 1 Stage 2 because the minimum number of responding subjects required to proceed to Part 2 was not reached. Further subject enrollment therefore ended after 78 subjects had been enrolled and treated on Part 1.
Participants by arm
| Arm | Count |
|---|---|
| 50 mg Sunitinib Sunitinib was administered orally daily for 4 weeks followed by a 2-week off-treatment period (Schedule 4 weeks on drug / 2 weeks off) in each cycle. The starting dose was 50 mg daily with provision for dose interruption and/or reduction based on tolerability. All subjects received repeated cycles of sunitinib until disease progression, occurrence of unacceptable toxicity, withdrawal of subject consent, or other withdrawal criteria were met. | 78 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Death | 8 |
| Overall Study | Lack of Efficacy | 55 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | 50 mg Sunitinib |
|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 78 / 78 |
| serious Total, serious adverse events | 30 / 78 |
Outcome results
Primary
Best Overall Response
Number of patients with best overall response = complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response. CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
Population: Intent-to-treat (ITT) population includes all patients enrolled in the study that received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50 mg Sunitinib | Best Overall Response | Complete Response | 0 participants |
| 50 mg Sunitinib | Best Overall Response | Partial Response | 2 participants |
| 50 mg Sunitinib | Best Overall Response | Stable Disease | 25 participants |
| 50 mg Sunitinib | Best Overall Response | Progressive Disease | 42 participants |
| 50 mg Sunitinib | Best Overall Response | Missing | 4 participants |
| 50 mg Sunitinib | Best Overall Response | Not Evaluable | 5 participants |
Primary
Objective Response (Complete Response (CR) or Partial Response (PR))
Number of patients with Objective Response (OR): confirmed CR or confirmed PR according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Sunitinib | Objective Response (Complete Response (CR) or Partial Response (PR)) | 2 participants |
95% CI: [0.3, 9]
Secondary
Clinical Benefit Response (CBR)-Complete Response (CR), Partial Response (PR) or Stable Disease (SD) With Duration ≥ 24 Weeks
Number of patients with Clinical Benefit Response: confirmed CR, confirmed PR or stable disease (SD) for at least 24 weeks on study according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. SD = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progessive disease (PD) taking as a reference the smallest sum of the longest dimensions since the treatment started.
Time frame: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or clinical benefit response for at least 24 weeks on study
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Sunitinib | Clinical Benefit Response (CBR)-Complete Response (CR), Partial Response (PR) or Stable Disease (SD) With Duration ≥ 24 Weeks | 6 participants |
95% CI: [2.9, 16]
Secondary
Duration of Response (CR or PR)
Time from the first documentation of confirmed objective response (CR or PR) to the first documentation of disease progression or to death due to any cause. CR = the disappearance of all target lesions. PR = a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: Day 28 of Cycle 1 and Day 28 of Cycles thereafter or death due to cancer
Population: ITT population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 50 mg Sunitinib | Duration of Response (CR or PR) | 16 weeks |
Secondary
Overall Survival
Time from the date of first dose of study medication to the date of death due to any cause. OS was calculated as (date of death minus the date of first dose date plus 1) divided by 7.
Time frame: From start of study treatment until death
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 mg Sunitinib | Overall Survival | 29.6 weeks |
Secondary
Progression-Free Survival
Time from start of study treatment to first documentation of objective tumor progression, or to death due to any cause. PFS was calculated as (first event date minus the date of first dose plus 1) divided by 7.
Time frame: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 mg Sunitinib | Progression-Free Survival | 10.0 weeks |
Secondary
Time to Tumor Progression (TTP)
Time from the start of study treatment to the first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose plus 1) divided by 7.
Time frame: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 50 mg Sunitinib | Time to Tumor Progression (TTP) | 10.1 weeks |