Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study (AbraxAvast)
Primary Purpose
Metastatic Malignant Melanoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Avastin
Abraxane
Sponsored by

About this trial
This is an interventional treatment trial for Metastatic Malignant Melanoma focused on measuring Metastatic malignant melanoma, First-line therapy
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed, (surgically incurable or unresectable) stage III or IV metastatic malignant melanoma..
- Must be chemo naïve. Surgical adjuvant therapy with interferon, vaccines, or cytokines is permitted. Prior adjuvant therapy with chemotherapeutic agents is not allowed. Prior therapy for metastatic disease that is not chemotherapy is allowed. Must have discontinued prior allowable therapy at least 4 weeks prior to initiation of dosing.
- A minimum of 1 measurable lesion according to RECIST criteria.
- ECOG performance status of 0-1.
- Age ≥ 18 years.
- Adequate hematologic, renal and liver function as defined by laboratory values performed within 14 days prior to initiation of dosing.
- Patients must have recovered from effects of major surgery.
- Women of childbearing potential should be using an effective method of contraception. Women of childbearing potential must have a negative urine or serum pregnancy test up to 28 days prior to commencement of dosing and be practicing medically approved contraceptive precautions for at least 6 months after completion of treatment as directed by their physician.
- Men should use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician.
- Must have recovered from all prior treatment-related toxicities to NCI CTCAE (v 3.0) Grade of 0 or 1, except for toxicities not considered a safety risk such as alopecia.
- Before study entry, written informed consent must be obtained. Written informed consent must be obtained from the patient prior to performing any study-related procedures.
Exclusion Criteria:
- Prior systemic therapy for metastatic disease with chemotherapy.
- Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
- Major surgery or radiation therapy within 4 weeks of starting the study treatment.
- Known CNS disease.
- Previous Grade 2 or higher sensory neuropathy
- NCI CTCAE (V 3.0) grade 3 hemorrhage within 4 weeks of starting the study treatment.
- History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.
- Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
- Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥ 2.
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
- Previous cancer (unless a DRS interval of at least 5 years) or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.
- Known clinically uncontrolled infectious disease including HIV positivity or AIDS-related illness.
- Pregnant or nursing. Use of effective means of contraception (men and women) in subjects of child-bearing potential.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- Symptomatic peripheral vascular disease.
- Significant vascular disease (e.g. aortic aneurysm, aortic dissection).
- Evidence of bleeding diathesis or coagulopathy.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
- Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
- Serious, non-healing wound, ulcer, or bone fracture
- Inability to comply with study and/or follow-up procedures
Sites / Locations
- Northern California Melanoma Center
- The Angeles Clinic and Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm, Open Label
Arm Description
Single Arm, Open Label trial of Abraxane and Avastin
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS) at 4 Months
Progression-free survival at 4 months from first treatment as determined by RECIST 1.0
Secondary Outcome Measures
Progression-free Survival
Median time of progression-free survival from first treatment according to RECIST 1.0
Overall Survival (OS)
The duration of overall survival was defined as the number of months between the start date of protocol treatment and the date of death (irrespective of cause), and was right-censored at the date of last contact for patients who were alive as of the data cutoff.
Objective Response Rate (RR) in Patients With Measurable Lesions Time to Objective Response
The objective response rate is defined as the percentage of patients showing complete or partial response.
Safety and Tolerability of This Combination
See adverse events Table
Full Information
NCT ID
NCT00462423
First Posted
April 18, 2007
Last Updated
January 7, 2014
Sponsor
Lynn E. Spitler, MD
Collaborators
Celgene Corporation, Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00462423
Brief Title
Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
Acronym
AbraxAvast
Official Title
Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
January 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lynn E. Spitler, MD
Collaborators
Celgene Corporation, Genentech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study is an open-label, single arm multicenter Phase II study to evaluate the safety and efficacy of the combination of Abraxane and Avastin as first-line therapy for patients with unresectable metastatic malignant melanoma. The patient sample will be approximately 50 individuals, males and females 18 years of age or older with measurable metastatic melanoma.
Patients will be treated with Abraxane administered weekly for 3 weeks via a 30-minute IV infusion at150 mg/m2 followed by 1 week rest (28-day cycle). Avastin will be administered in a dose of 10 mg/kg every 2 weeks (without rest period). Patients will be evaluated for disease progression every 2 months and those who do not have disease progression or unacceptable toxicity will be offered ongoing therapy until they have progressive disease or unacceptable toxicity.
Detailed Description
It has been suggested that chemotherapy administration may be synergistic with the effects of an antiangiogenic agent such as Avastin. A "Proof of Principal" of the concept of the synergistic effects of chemotherapy and antiangiogenic therapy has been shown in the favorable results reported with temozolomide administered in combination with thalidomide in melanoma, the favorable results reported for the use of FOLFOX4 in combination with Avastin in previously treated patients with advanced or metastatic colorectal cancer, and the approval of the combination of Avastin with 5-fluorouracil-based chemotherapy in the treatment of patients with metastatic carcinoma of the colon or rectum.
A number of lines of evidence suggest that the combination of Abraxane and Avastin may be effective as first-line therapy for melanoma:
Taxanes are active agents in melanoma:
In a clinical trial in patients who had failed combination chemotherapy (the Dartmouth regimen, there was a 24% response rate in patients treated with paclitaxel (in combination with tamoxifen).
Paclitaxel is being used in a Phase III trial with carboplatin and Sorafenib in patients with metastatic melanoma who have failed no more than one previous systemic chemotherapeutic treatment.
In a phase II trial of docetaxel in patients with metastatic melanoma, objective responses lasting more than 2 years were observed.
Abraxane is a taxane that has efficacy superior to that of Taxol for the treatment of metastatic breast cancer. Abraxane was evaluated as first- and second-line therapy for patients with metastatic melanoma. Results were encouraging. In this study, Abraxane will be combined with Avastin in an effort to improve the clinical benefit and prolong the time to disease progression.
The primary end-point of the study is progression-free survival (PFS) at 4 months. Secondary end-points include progression-free survival, overall survival (OS), objective Response Rate (RR) in patients with measurable lesions, time to objective response, duration of objective response in patients with measurable lesions, and safety and tolerability of this combination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Malignant Melanoma
Keywords
Metastatic malignant melanoma, First-line therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm, Open Label
Arm Type
Experimental
Arm Description
Single Arm, Open Label trial of Abraxane and Avastin
Intervention Type
Drug
Intervention Name(s)
Avastin
Other Intervention Name(s)
Avastin: bevacizumab.
Intervention Description
Avastin 10 mg/kg IV every 2 weeks (without rest period).
Intervention Type
Drug
Intervention Name(s)
Abraxane
Intervention Description
Abraxane 150 mg/m2 IV weekly for 3 weeks of a 28-day cycle.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) at 4 Months
Description
Progression-free survival at 4 months from first treatment as determined by RECIST 1.0
Time Frame
4 months.
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Median time of progression-free survival from first treatment according to RECIST 1.0
Time Frame
From start of treatment to disease progressin; median duration of follow-up for surviving patients was 41.6 months.
Title
Overall Survival (OS)
Description
The duration of overall survival was defined as the number of months between the start date of protocol treatment and the date of death (irrespective of cause), and was right-censored at the date of last contact for patients who were alive as of the data cutoff.
Time Frame
April 2007 through December 2010
Title
Objective Response Rate (RR) in Patients With Measurable Lesions Time to Objective Response
Description
The objective response rate is defined as the percentage of patients showing complete or partial response.
Time Frame
The median duration of follow-up for surviving patients was 41.6 months.
Title
Safety and Tolerability of This Combination
Description
See adverse events Table
Time Frame
April 2007 through December 2010
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed, (surgically incurable or unresectable) stage III or IV metastatic malignant melanoma..
Must be chemo naïve. Surgical adjuvant therapy with interferon, vaccines, or cytokines is permitted. Prior adjuvant therapy with chemotherapeutic agents is not allowed. Prior therapy for metastatic disease that is not chemotherapy is allowed. Must have discontinued prior allowable therapy at least 4 weeks prior to initiation of dosing.
A minimum of 1 measurable lesion according to RECIST criteria.
ECOG performance status of 0-1.
Age ≥ 18 years.
Adequate hematologic, renal and liver function as defined by laboratory values performed within 14 days prior to initiation of dosing.
Patients must have recovered from effects of major surgery.
Women of childbearing potential should be using an effective method of contraception. Women of childbearing potential must have a negative urine or serum pregnancy test up to 28 days prior to commencement of dosing and be practicing medically approved contraceptive precautions for at least 6 months after completion of treatment as directed by their physician.
Men should use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician.
Must have recovered from all prior treatment-related toxicities to NCI CTCAE (v 3.0) Grade of 0 or 1, except for toxicities not considered a safety risk such as alopecia.
Before study entry, written informed consent must be obtained. Written informed consent must be obtained from the patient prior to performing any study-related procedures.
Exclusion Criteria:
Prior systemic therapy for metastatic disease with chemotherapy.
Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
Major surgery or radiation therapy within 4 weeks of starting the study treatment.
Known CNS disease.
Previous Grade 2 or higher sensory neuropathy
NCI CTCAE (V 3.0) grade 3 hemorrhage within 4 weeks of starting the study treatment.
History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.
Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
Ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade ≥ 2.
Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
Any prior history of hypertensive crisis or hypertensive encephalopathy
Concurrent treatment on another clinical trial. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
Previous cancer (unless a DRS interval of at least 5 years) or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.
Known clinically uncontrolled infectious disease including HIV positivity or AIDS-related illness.
Pregnant or nursing. Use of effective means of contraception (men and women) in subjects of child-bearing potential.
New York Heart Association (NYHA) Grade II or greater congestive heart failure.
Symptomatic peripheral vascular disease.
Significant vascular disease (e.g. aortic aneurysm, aortic dissection).
Evidence of bleeding diathesis or coagulopathy.
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
Serious, non-healing wound, ulcer, or bone fracture
Inability to comply with study and/or follow-up procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lynn E. Spitler, MD
Organizational Affiliation
Northern California Melanoma Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northern California Melanoma Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
The Angeles Clinic and Research Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
15175435
Citation
Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. doi: 10.1056/NEJMoa032691.
Results Reference
background
PubMed Identifier
16172456
Citation
Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. doi: 10.1200/JCO.2005.04.937. Epub 2005 Sep 19.
Results Reference
background
Links:
URL
http://www.melanomacenter.com
Description
Link to Northern California Melanoma Center Website
Learn more about this trial
Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
We'll reach out to this number within 24 hrs