Metastatic Malignant MelanomaPhase 2AbraxAvastNCT00462423
Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
A Phase 2 study testing Avastin and Abraxane in people with Metastatic Malignant Melanoma, run by Lynn E. Spitler, MD at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Melanoma
- What is being tested?
- Avastin and Abraxane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2007to Jan 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 26Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northern California Melanoma Center
San Francisco, California, 94117
The Angeles Clinic and Research Institute
Santa Monica, California, 90404
About this study
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.
Read the 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.
- Conditions
- Metastatic Malignant Melanoma
- Being tested
- Avastin, Abraxane
- Keywords
- Metastatic malignant melanoma, First-line therapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvastinDrug
Also called Avastin: bevacizumab.
Avastin 10 mg/kg IV every 2 weeks (without rest period).
AbraxaneDrug
Abraxane 150 mg/m2 IV weekly for 3 weeks of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm, Open Label | Experimental | Single Arm, Open Label trial of Abraxane and Avastin Receives: Drug: Avastin; Drug: Abraxane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) at 4 Months
Progression-free survival at 4 months from first treatment as determined by RECIST 1.0
Measured: 4 months.
Secondary outcomes (4)
Progression-free Survival
Median time of progression-free survival from first treatment according to RECIST 1.0
Measured: From start of treatment to disease progressin; median duration of follow-up for surviving patients was 41.6 months.
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.
Measured: April 2007 through December 2010
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.
Measured: The median duration of follow-up for surviving patients was 41.6 months.
Safety and Tolerability of This Combination
See adverse events Table
Measured: April 2007 through December 2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionApr 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lynn E. Spitler, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation, Genentech, Inc.
- Responsible party
- Sponsor-investigator, Lynn E. Spitler, MD, Northern California Melanoma Center
- Investigators
- Lynn E. Spitler, MD, Principal investigator, Northern California Melanoma Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00462423
- Sponsor's protocol ID
- 070223
- Acronym
- AbraxAvast
- Status last verified
- Jan 2014
- First submitted
- 18 Apr 2007
- Last updated
- 8 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 15175435Gradishar 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.
PubMed 16172456
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
- ClinicalTrials.gov ID
- NCT00462423
- Acronym / sponsor ID
- AbraxAvast / 070223
- Conditions
- Metastatic Malignant Melanoma
- Keywords
- Metastatic malignant melanoma, First-line therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Lynn E. Spitler, MDUniversity, hospital or other
- Collaborators
- Celgene Corporation, Genentech, Inc.
- Study start
- Apr 2007
- Primary completion
- Apr 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 19 Apr 2007 (estimated)
- Results
- Posted 8 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm, Open Label | Experimental | Drug: Avastin, Drug: AbraxaneSingle Arm, Open Label trial of Abraxane and Avastin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvastinAlso: Avastin: bevacizumab.Avastin 10 mg/kg IV every 2 weeks (without rest period). | Drug | Single Arm, Open Label |
| AbraxaneAbraxane 150 mg/m2 IV weekly for 3 weeks of a 28-day cycle. | Drug | Single Arm, Open Label |
Primary outcome
Progression-free Survival (PFS) at 4 Months
Time frame: 4 months.
Progression-free survival at 4 months from first treatment as determined by RECIST 1.0
4 secondary outcomes
Progression-free Survival
Time frame: From start of treatment to disease progressin; median duration of follow-up for surviving patients was 41.6 months.
Overall Survival (OS)
Time frame: April 2007 through December 2010
Objective Response Rate (RR) in Patients With Measurable Lesions Time to Objective Response
Time frame: The median duration of follow-up for surviving patients was 41.6 months.
Safety and Tolerability of This Combination
Time frame: April 2007 through December 2010
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15175435Hurwitz 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.
- Background: PubMed 16172456Gradishar 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.
- Link to Northern California Melanoma Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynn E. Spitler, MD principal investigator
Northern California Melanoma Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avastin and Abraxane in people with Metastatic Malignant Melanoma, run by Lynn E. Spitler, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) at 4 Months (time frame: 4 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00462423, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2014.