Trial Outcomes & Findings for An International Phase 2 Study Of SU011248 In Patients With Advanced / Metastatic Gastric Cancer Failing Chemotherapy (NCT NCT00226811)

Last Updated: 2015-03-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

78 participants

Primary outcome timeframe

From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter

Results posted on

2015-03-30

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	78
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	76

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Death	8
Overall Study Adverse Event	11
Overall Study Lack of Efficacy	55
Overall Study Withdrawal by Subject	2

Baseline Characteristics

An International Phase 2 Study Of SU011248 In Patients With Advanced / Metastatic Gastric Cancer Failing Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	50 mg Sunitinib n=78 Participants 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.
Age, Continuous	55.1 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=78 Participants 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.
Best Overall Response Complete Response	0 participants
Best Overall Response Partial Response	2 participants
Best Overall Response Stable Disease	25 participants
Best Overall Response Progressive Disease	42 participants
Best Overall Response Not Evaluable	5 participants
Best Overall Response Missing	4 participants

PRIMARY outcome

Timeframe: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=78 Participants 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.
Objective Response (Complete Response (CR) or Partial Response (PR))	2 participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=78 Participants 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.
Clinical Benefit Response (CBR)-Complete Response (CR), Partial Response (PR) or Stable Disease (SD) With Duration ≥ 24 Weeks	6 participants

SECONDARY outcome

Timeframe: Day 28 of Cycle 1 and Day 28 of Cycles thereafter or death due to cancer

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=2 Participants 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.
Duration of Response (CR or PR)	16 weeks Interval 6.0 to 26.0

SECONDARY outcome

Timeframe: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=78 Participants 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.
Progression-Free Survival	10.0 weeks Interval 6.9 to 11.1

SECONDARY outcome

Timeframe: From start of study treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=78 Participants 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.
Time to Tumor Progression (TTP)	10.1 weeks Interval 7.29 to 11.29

SECONDARY outcome

Timeframe: From start of study treatment until death

Population: ITT population

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.

Outcome measures

Outcome measures
Measure	50 mg Sunitinib n=78 Participants 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.
Overall Survival	29.6 weeks Interval 19.1 to 42.0

Adverse Events

50 mg Sunitinib

Serious events: 30 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	50 mg Sunitinib n=78 participants at risk 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.
Blood and lymphatic system disorders Anaemia	2.6% 2/78
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.3% 1/78
Blood and lymphatic system disorders Thrombocytopenia	3.8% 3/78
Cardiac disorders Cardiac arrest	1.3% 1/78
Cardiac disorders Sinus bradycardia	1.3% 1/78
Eye disorders Heterophoria	1.3% 1/78
Gastrointestinal disorders Abdominal pain	3.8% 3/78
Gastrointestinal disorders Abdominal pain upper	1.3% 1/78
Gastrointestinal disorders Ascites	2.6% 2/78
Gastrointestinal disorders Ileus	1.3% 1/78
Gastrointestinal disorders Nausea	1.3% 1/78
Gastrointestinal disorders Peritonitis	2.6% 2/78
Gastrointestinal disorders Salivary gland pain	1.3% 1/78
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.6% 2/78
Gastrointestinal disorders Vomiting	5.1% 4/78
General disorders Disease progression	7.7% 6/78
General disorders Fatigue	2.6% 2/78
General disorders Malaise	1.3% 1/78
General disorders Mucosal inflammation	2.6% 2/78
General disorders Performance status decreased	1.3% 1/78
General disorders Pyrexia	2.6% 2/78
Hepatobiliary disorders Hepatic function abnormal	1.3% 1/78
Hepatobiliary disorders Hyperbilirubinaemia	1.3% 1/78
Hepatobiliary disorders Jaundice	1.3% 1/78
Hepatobiliary disorders Jaundice cholestatic	1.3% 1/78
Infections and infestations Infection	1.3% 1/78
Infections and infestations Pneumonia	2.6% 2/78
Injury, poisoning and procedural complications Brain herniation	1.3% 1/78
Injury, poisoning and procedural complications Overdose	1.3% 1/78
Injury, poisoning and procedural complications Stent occlusion	1.3% 1/78
Metabolism and nutrition disorders Anorexia	3.8% 3/78
Metabolism and nutrition disorders Dehydration	1.3% 1/78
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour compression	1.3% 1/78
Nervous system disorders Brain stem haemorrhage	1.3% 1/78
Nervous system disorders Cerebral infarction	1.3% 1/78
Psychiatric disorders Suicidal ideation	1.3% 1/78
Respiratory, thoracic and mediastinal disorders Hypopnoea	1.3% 1/78
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/78
Respiratory, thoracic and mediastinal disorders respiratory failure	1.3% 1/78
Vascular disorders Hypotension	1.3% 1/78

Other adverse events

Other adverse events
Measure	50 mg Sunitinib n=78 participants at risk 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.
Blood and lymphatic system disorders Anaemia	38.5% 30/78
Blood and lymphatic system disorders Leukopenia	38.5% 30/78
Blood and lymphatic system disorders Lymphopenia	14.1% 11/78
Blood and lymphatic system disorders Neutropenia	52.6% 41/78
Blood and lymphatic system disorders Thrombocytopenia	57.7% 45/78
Gastrointestinal disorders Abdominal distension	10.3% 8/78
Gastrointestinal disorders Abdominal pain	25.6% 20/78
Gastrointestinal disorders Abdominal pain upper	5.1% 4/78
Gastrointestinal disorders Constipation	21.8% 17/78
Gastrointestinal disorders Diarrhoea	37.2% 29/78
Gastrointestinal disorders Dry mouth	5.1% 4/78
Gastrointestinal disorders Dyspepsia	14.1% 11/78
Gastrointestinal disorders Gingivitis	5.1% 4/78
Gastrointestinal disorders Nausea	39.7% 31/78
Gastrointestinal disorders Stomatitis	35.9% 28/78
Gastrointestinal disorders Vomiting	28.2% 22/78
General disorders Asthenia	9.0% 7/78
General disorders Face oedema	5.1% 4/78
General disorders Fatigue	44.9% 35/78
General disorders Malaise	5.1% 4/78
General disorders Mucosal inflammation	14.1% 11/78
General disorders Oedema	9.0% 7/78
General disorders Oedema peripheral	12.8% 10/78
General disorders Pyrexia	25.6% 20/78
Hepatobiliary disorders Hyperbilirubinaemia	16.7% 13/78
Infections and infestations Nasopharyngitis	5.1% 4/78
Investigations Alanine aminotransferase increased	9.0% 7/78
Investigations Aspartate aminotransferase increased	15.4% 12/78
Investigations Blood alkaline phosphatase increased	14.1% 11/78
Investigations C-reactive protein increased	6.4% 5/78
Investigations Red blood cell count decreased	6.4% 5/78
Investigations Weight decreased	10.3% 8/78
Metabolism and nutrition disorders Anorexia	46.2% 36/78
Metabolism and nutrition disorders Hypoalbuminaemia	19.2% 15/78
Metabolism and nutrition disorders Hypocalcaemia	6.4% 5/78
Metabolism and nutrition disorders Hypokalaemia	5.1% 4/78
Metabolism and nutrition disorders Hyponatraemia	6.4% 5/78
Metabolism and nutrition disorders Hypoproteinaemia	7.7% 6/78
Musculoskeletal and connective tissue disorders Back pain	11.5% 9/78
Nervous system disorders Dizziness	6.4% 5/78
Nervous system disorders Dysgeusia	9.0% 7/78
Nervous system disorders Headache	7.7% 6/78
Nervous system disorders Peripheral sensory neuropathy	5.1% 4/78
Psychiatric disorders Insomnia	11.5% 9/78
Respiratory, thoracic and mediastinal disorders Cough	5.1% 4/78
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.3% 8/78
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 6/78
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	11.5% 9/78
Skin and subcutaneous tissue disorders Alopecia	6.4% 5/78
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	28.2% 22/78
Skin and subcutaneous tissue disorders Pruritus	6.4% 5/78
Skin and subcutaneous tissue disorders Rash	17.9% 14/78
Skin and subcutaneous tissue disorders Skin discolouration	24.4% 19/78
Skin and subcutaneous tissue disorders Skin exfoliation	5.1% 4/78
Skin and subcutaneous tissue disorders Skin lesion	5.1% 4/78
Skin and subcutaneous tissue disorders Yellow skin	7.7% 6/78
Vascular disorders Hypertension	14.1% 11/78
Gastrointestinal disorders Ascites	10.3% 8/78

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
Publication restrictions are in place

Restriction type: OTHER