Trial Outcomes & Findings for VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium (NCT NCT00407485)

Last Updated: 2014-10-20

Results Overview

Response rate (RR) and progression free survival (PFS) were assessed in a 2-stage accrual design (22+18). A maximum of 40 patients were to be accrued to rule out a null hypothesized RR of 4% and PFS of 3 months versus alternative of 15% RR and 5.4 months PFS (corresponding to 4 month PFS of 40% vs 60%) with α=0.12 and β=0.19. If no more than 1 objective response (no more than 4.5%), and no more than 10 instances of 4-month PFS (no more than 45%), were observed among the initial 22 patients, the study would be terminated early and declared negative. Tumor response was evaluated by CT or MRI using RECIST v1.0 criteria. Responders were confirmed partial or complete responses to treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

From the start of the treatment until disease progression or recurrence, assessed up to 4 years

Results posted on

2014-10-20

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Ziv-aflibercept) Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. ziv-aflibercept: Given IV pharmacological study: Correlative studies
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Ziv-aflibercept) n=22 Participants Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. ziv-aflibercept: Given IV pharmacological study: Correlative studies
Age, Continuous	67 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	20 participants n=5 Participants
Race/Ethnicity, Customized Americian Indian	1 participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	1 participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of the treatment until disease progression or recurrence, assessed up to 4 years

Outcome measures

Outcome measures
Measure	Treatment (Ziv-aflibercept) n=22 Participants Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. ziv-aflibercept: Given IV pharmacological study: Correlative studies
Tumor Response Rate	4.5 percentage of responders Interval 0.1 to 22.8

PRIMARY outcome

Timeframe: From start of treatment to time of progression, assessed up to 4 months

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions PFS using the product-limit method of Kaplan and Meier.

Outcome measures

Outcome measures
Measure	Treatment (Ziv-aflibercept) n=22 Participants Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. ziv-aflibercept: Given IV pharmacological study: Correlative studies
Progression-free Survival (PFS)	2.79 Months Interval 1.74 to 3.88

Adverse Events

Treatment (Ziv-aflibercept)

Serious events: 4 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ziv-aflibercept) n=22 participants at risk Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. ziv-aflibercept: Given IV pharmacological study: Correlative studies
Gastrointestinal disorders Abdominal pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Back pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Reproductive system and breast disorders Pelvic pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events

Other adverse events
Measure	Treatment (Ziv-aflibercept) n=22 participants at risk Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. ziv-aflibercept: Given IV pharmacological study: Correlative studies
Blood and lymphatic system disorders Hemoglobin decreased	54.5% 12/22 • Number of events 34 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	13.6% 3/22 • Number of events 5 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	31.8% 7/22 • Number of events 11 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	27.3% 6/22 • Number of events 13 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dry mouth	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dyspepsia	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Enteritis	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastritis	4.5% 1/22 • Number of events 3 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gingival pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	4.5% 1/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	36.4% 8/22 • Number of events 10 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral pain	9.1% 2/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Stomach pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Toothache	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	22.7% 5/22 • Number of events 5 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	9.1% 2/22 • Number of events 3 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Death	31.8% 7/22 • Number of events 7 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Disease progression	9.1% 2/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	9.1% 2/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	72.7% 16/22 • Number of events 51 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	13.6% 3/22 • Number of events 7 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Bladder infection	4.5% 1/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Sinusitis	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Tooth infection	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Activated partial thromboplastin time prolonged	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alanine aminotransferase increased	40.9% 9/22 • Number of events 21 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alkaline phosphatase increased	36.4% 8/22 • Number of events 31 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	40.9% 9/22 • Number of events 16 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Bilirubin increased	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations CD4 lymphocytes decreased	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	59.1% 13/22 • Number of events 42 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Leukocyte count decreased	9.1% 2/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	36.4% 8/22 • Number of events 21 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	4.5% 1/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Weight loss	13.6% 3/22 • Number of events 5 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Anorexia	45.5% 10/22 • Number of events 29 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Blood bicarbonate decreased	9.1% 2/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Blood glucose increased	63.6% 14/22 • Number of events 34 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Blood uric acid increased	13.6% 3/22 • Number of events 9 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperglycemia	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum albumin decreased	31.8% 7/22 • Number of events 13 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum calcium decreased	22.7% 5/22 • Number of events 10 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum calcium increased	9.1% 2/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum glucose decreased	18.2% 4/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum phosphate decreased	22.7% 5/22 • Number of events 7 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum potassium decreased	4.5% 1/22 • Number of events 3 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum potassium increased	36.4% 8/22 • Number of events 15 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum sodium decreased	36.4% 8/22 • Number of events 15 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Serum sodium increased	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Back pain	31.8% 7/22 • Number of events 18 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Chest wall pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Joint pain	18.2% 4/22 • Number of events 9 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Neck pain	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	4.5% 1/22 • Number of events 7 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Dizziness	13.6% 3/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Headache	45.5% 10/22 • Number of events 20 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Peripheral sensory neuropathy	13.6% 3/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Taste alteration	4.5% 1/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Anxiety	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Psychiatric disorders Insomnia	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Hemoglobin urine positive	4.5% 1/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Hemorrhage urinary tract	22.7% 5/22 • Number of events 9 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Protein urine positive	36.4% 8/22 • Number of events 17 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary incontinence	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urine discoloration	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 2/22 • Number of events 8 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	13.6% 3/22 • Number of events 6 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hiccough	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	4.5% 1/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Voice alteration	18.2% 4/22 • Number of events 9 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Dry skin	9.1% 2/22 • Number of events 4 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	9.1% 2/22 • Number of events 3 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Pruritus	4.5% 1/22 • Number of events 1 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash desquamating	9.1% 2/22 • Number of events 3 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Skin disorder	4.5% 1/22 • Number of events 2 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Urticaria	4.5% 1/22 • Number of events 3 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypertension	63.6% 14/22 • Number of events 28 "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Additional Information

DCC Project Administrator

California Cancer Consortium

Phone: 626-256-4673

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60