Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study
Condition: Metastatic Malignant Melanoma
MeSH terms: Melanoma
Intervention: Avastin; Abraxane
Intervention description: Avastin 10 mg/kg IV every 2 weeks (without rest period).; Abraxane 150 mg/m2 IV weekly for 3 weeks of a 28-day cycle.
Intervention MeSH terms: Bevacizumab; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic malignant melanoma; First-line therapy

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.
    

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