Combo of Abraxane, TMZ, Bevacizumab in Metastatic Melanoma With Brain Metastases

NCT02065466 | Withdrawn Phase 1 DMC

• 1 other identifier: 1312169092
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

1.1. Primary Objectives 1\. To determine if nab-paclitaxel and temozolomide can be combined with full dose of bevacizumab for the therapy of patients with newly diagnosed brain metastases of metastatic malignant melanoma.

• To define the MTD of the combination (Phase I component).
• To determine progression free survival (Phase II component). 1.2. Secondary Objectives
• To separately evaluate the response rate and duration of both the brain and extra-cranial systemic metastases.
• To define the toxicity of the regimen.
• To tabulate the toxicity of the radiotherapy to the brain and compare with known toxicities of radiotherapy to the brain in melanoma and brain metastases.
• To use the data generated to plan definitive controlled clinical trials of the combination.
• To determine the overall response rate (Phase II component).

Conditions

Metastatic Melanoma; Brain Metastases

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerance Dose

  To define the MTD of the combination (Phase I component).

  Beginning of Treatment to unstable disease or discontinuation (6 months)

• Progression Free Survival

  To determine progression free survival (Phase II component).

  Treatment to End of Follow-up (6 Months)

Secondary Outcomes (1)

• Response Rate

  Baseline to end of follow-up (six months)

Study Arms (1)

Combination

EXPERIMENTAL

nab-paclitaxel and temozolomide combined with full dose of bevacizumab

Drug: nab-paclitaxel; Drug: Temozolomide; Drug: Bevacizumab

Interventions

nab-paclitaxel DRUG

Combination

Temozolomide DRUG

Combination

Bevacizumab DRUG

Combination

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed malignant melanoma and clinical evidence of metastatic disease to the brain. Mucosal and ocular melanomas are included.
• Newly developed inoperable brain metastases without associated hemorrhage or midline shift.
• Inoperable or metastatic extra cranial stage III or IV disease.
• Diagnostic quality MRI of the brain or if contraindicated then contrast CT scan of the head performed within 28 days prior to registration.
• Measurable metastases to the brain, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm in the brain MRI/CT scan.
• CT scan chest, abdomen and pelvis or PET CT scan performed within 28 days of study registration. For disease outside the brain, tumors must be \> 10 mm by CT scan.
• Prior therapy allowed but no prior therapy with nab-paclitaxel, paclitaxel, temozolomide, DTIC or bevacizumab.
• Bevacizumab may not be initiated until 4 weeks after surgical resection or radiation therapy completion.
• Age 18 or older.
• Pre-existing peripheral neuropathy must have \< Grade 2 (per CTCAE 4.0) at the time of registration.
• Negative serum or urine β-hCG pregnancy test at screening for patients of childbearing potential.
• Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.
• ECOG Performance status 0-1.
• Estimated life expectancy of greater than 2 months.
• Patients must have adequate organ function as defined below (these must be evaluated within 14 days prior to registration):

You may not qualify if:

• Prior surgical resection for brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, nab-paclitaxel or temozolomide.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, untreated cardiac arrhythmia and peripheral vascular disease.
• 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.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study screening.
• Serious, non-healed wound, ulcer, or bone fracture.
• History of hepatitis B, C or HIV.
• Uncontrolled hypertension or chronic renal disease. No known bleeding diathesis.
• Known hypersensitivity to human albumin.
• Surgery within 4 weeks of study registration. Must be fully recovered and fully healed from any prior surgery.
• Patients having chemotherapy or extra cranial radiotherapy within 4 weeks prior to study screening or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to the completion of study screening.
• Evidence of other concurrent active malignancy.
• Pregnant or nursing.
• Not be receiving any other investigational agent.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (2)

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, 85724-5024, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85742, United States

Location

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Temozolomide; Bevacizumab

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; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lee Cranmer, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 19, 2014
• Study Start: July 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: August 1, 2015
• Last Updated: April 21, 2016

Record last verified: 2016-04

Locations

US (2)