Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study

NCT00462423 | Completed Phase 2 Results DMC

• 1 other identifier: 070223
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Metastatic Malignant Melanoma

Keywords

Metastatic malignant melanoma; First-line therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) at 4 Months

  Progression-free survival at 4 months from first treatment as determined by RECIST 1.0

  4 months.

Secondary Outcomes (4)

• Progression-free Survival

  From start of treatment to disease progressin; median duration of follow-up for surviving patients was 41.6 months.

• Overall Survival (OS)

  April 2007 through December 2010

• Objective Response Rate (RR) in Patients With Measurable Lesions Time to Objective Response

  The median duration of follow-up for surviving patients was 41.6 months.

• Safety and Tolerability of This Combination

  April 2007 through December 2010

Study Arms (1)

Single Arm, Open Label

EXPERIMENTAL

Single Arm, Open Label trial of Abraxane and Avastin

Drug: Avastin; Drug: Abraxane

Interventions

Avastin DRUG

Avastin 10 mg/kg IV every 2 weeks (without rest period).

Also known as: Avastin: bevacizumab.

Single Arm, Open Label

Abraxane DRUG

Abraxane 150 mg/m2 IV weekly for 3 weeks of a 28-day cycle.

Single Arm, Open Label

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lynn E. Spitler, MD: lead
• Celgene Corporation: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Northern California Melanoma Center

San Francisco, California, 94117, United States

Location

The Angeles Clinic and Research Institute

Santa Monica, California, 90404, United States

Location

Related Publications (2)

• 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.

  PMID: 15175435 BACKGROUND

• 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.

  PMID: 16172456 BACKGROUND

Related Links

• Link to Northern California Melanoma Center Website

MeSH Terms

Conditions

Melanoma

Interventions

Bevacizumab; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This was a single arm study. Follow-up trials to further explore this regimen are warranted.

Results Point of Contact

• Title: Lynn E. Spitler, MD
• Organization: Northern California Medical Center

lynn@drspitler.com

415-435-9861

Study Officials

• Lynn E. Spitler, MD

  Northern California Melanoma Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 19, 2007
• Study Start: April 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: January 1, 2012
• Last Updated: January 8, 2014
• Results First Posted: January 8, 2014

Record last verified: 2014-01

Locations

US (2)