Paclitaxel + Bevacizumab (Avastin) for the Treatment of Metastatic or Unresectable Angiosarcoma

NCT01055028 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-17755SU-01202010-4743SARCOMA0006
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, single-arm, multi-center, Phase 2 study with Paclitaxel in combination with Bevacizumab in patients with Unresectable or Metastatic Angiosarcoma. The study aims to determine the safety and effectiveness of combining two drugs Paclitaxel and Bevacizumab in the treatment of Angiosarcoma that cannot be removed by surgery, or has spread to other parts of your body. The primary objective is to evaluate 4month non progression rate. The secondary objective is to evaluate overall response rate after 3rd and 6th cycle, median duration of response, 6th and 12th month survival, toxicity of Paclitaxel and Bevacizumab combination, toxicity of maintenance Bevacizumab and to collect paraffin-embedded tumor blocks for angiogenesis markers and tissue microarray.

Conditions

Angiosarcomas; Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  The primary objective of this study was to evaluate progression-free survival (PFS or non-progression rate) through 4 months from start of treatment. Progression is defined as ≥ 20% increase in the sum of the longest diameter of target lesions, as compared to the baseline measurements, and/or the appearance of one or more new lesion(s).

  4 months

Secondary Outcomes (4)

• Overall Response Rate After 3 Cycles

  12 weeks

• Overall Response Rate After 6th Cycle

  6 Cycles

• Overall Survival (OS) at 6 Months

  6 months

• Overall Survival (OS) at 12 Months

  12 months

Study Arms (2)

Regimen A / Treatment 1

EXPERIMENTAL

Participants were to receive paclitaxel 200 mg/m² intravenously over 3 hours every 21 days followed by bevacizumab 15 mg/kg intravenously over (cycle 1: 90 min; cycle 2: 60 min; cycles 3 to 6: 30 min) every 21 days x 6 cycles. Maintenance bevacizumab (MB), 15 mg/kg once every 21 days intravenously for a maximum of 8 cycles, was initiated after the completion of paclitaxel + bevacizumab combination.

Drug: Bevacizumab; Drug: Paclitaxel

Regimen B / Treatment 2

EXPERIMENTAL

Patients were to receive paclitaxel 90 mg/m² weekly x 3 of a 28-day cycle followed by bevacizumab 15 mg/kg intravenously over (cycle 1: 90 min; cycle 2: 60 min; cycles 3 to 6: 30 min) every 21 days x 6 cycles. Maintenance bevacizumab (MB), 15 mg/kg once every 21 days intravenously for a maximum of 8 cycles, was initiated after the completion of paclitaxel + bevacizumab combination.

Drug: Bevacizumab; Drug: Paclitaxel

Interventions

Bevacizumab DRUG

15 mg/kg, IV every 21 days x 6 cycles.

Also known as: Avastin

Regimen A / Treatment 1; Regimen B / Treatment 2

Paclitaxel DRUG

Regimen A / Treatment 1: 200 mg/m² IV over 3 hours every 21 days. Regimen B / Treatment 2: 90 mg/m² weekly x 3 of a 28-day cycle

Also known as: Abraxane

Regimen A / Treatment 1; Regimen B / Treatment 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study. Abnormal PET scans will not constitute evaluable disease, unless verified by computed tomography (CT) scan or other appropriate imaging
• At least 1 objective measurable disease parameter by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
• Unresectable locally advanced or metastatic angiosarcoma
• ≤ 2 prior chemotherapeutic regimens for angiosarcoma
• No prior paclitaxel, docetaxel, or bevacizumab for angiosarcoma (previous paclitaxel or docetaxel allowed if not given for angiosarcoma and more than 12 months has elapsed since last dose)
• No evidence of other active malignancies other than carcinomas in-situ of the cervix or basal cell carcinoma of the skin within 6 months prior to registration
• If history of deep venous thrombosis or pulmonary embolism, receiving a stable dose of anticoagulation therapy for at least 2 weeks prior to registration
• Within 7 days prior to registration, use of any anti-platelet drugs, such as ticlopidine, clopidogrel, and cilostazol. The use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is allowed
• ECOG performance status 0 to 2
• Patients must have adequate organ function as evidenced by the following laboratory studies (within 2 weeks prior to registration):
• Serum creatinine ≤ 2.0 mg/dL
• Total bilirubin ≤ 2.0 x upper limit of normal (ULN). If documented hepatic involvement, can be ≤ 3 x ULN
• Serum glutamic oxaloacetic transaminase (SGOT) or Aspartate aminotransferase (AST) \< 2 x ULN. If documented hepatic involvement, can be ≤ 5 x ULN
• Absolute neutrophil count ≥ 1500/mm3 and platelet count \> 100,000/mm3
• Platelets ≤ 1.5 x ULN

You may not qualify if:

• Life expectancy \< 12 weeks
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an another experimental drug study
• Inadequately-controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• History of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1
• Known central nervous system (CNS) disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
• Significant vascular disease (eg, aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
• Serious, non-healing wound, active ulcer, or untreated bone fracture

Sponsors & Collaborators

• Stanford University: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Santa Monica Sarcoma Center

Santa Monica, California, 90403, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

MD Anderson Sarcoma Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hemangiosarcoma; Sarcoma

Interventions

Bevacizumab; Paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins

Results Point of Contact

• Title: Kristen Ganjoo, MD
• Organization: Stanford University Medical Center

kganjoo@stanford.edu

650-725-6413

Study Officials

• Kristen N Ganjoo, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 21, 2010
• First Posted: January 25, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2016
• Study Completion: June 24, 2016
• Last Updated: March 26, 2018
• Results First Posted: March 26, 2018

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)