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Sorafenib, Carboplatin, and Paclitaxel in Treating Patients With Stage IV Melanoma of the Eye

Phase II Trial of BAY 43-9006 (Sorafenib; NSC-724772) in Combination With Carboplatin and Paclitaxel in Patients With Metastatic Uveal Melanoma

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00329641
Enrollment
25
Registered
2006-05-25
Start date
2011-02-28
Completion date
2012-11-30
Last updated
2014-07-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ciliary Body and Choroid Melanoma, Medium/Large Size, Extraocular Extension Melanoma, Iris Melanoma, Metastatic Intraocular Melanoma, Recurrent Intraocular Melanoma

Brief summary

This phase II trial is studying how well sorafenib works when given together with carboplatin and paclitaxel in treating patients with stage IV melanoma of the eye. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may help carboplatin and paclitaxel work better by making tumor cells more sensitive to the drugs. Sorafenib may also stop the growth of melanoma by blocking some of the enzymes needed for tumor cell growth and by blocking blood flow to the tumor. Giving sorafenib together with carboplatin and paclitaxel may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. Determine the response rate (confirmed and unconfirmed, complete and partial response) of patients with stage IV uveal melanoma treated with sorafenib, carboplatin, and paclitaxel. SECONDARY OBJECTIVES: I. Determine the overall and progression-free survival of patients treated with this regimen. II. Determine the toxic effects of this regimen in these patients. III. Determine, preliminarily, the relationship between clinical outcomes and baseline microvessel density (MVD) in tumor specimens, changes in vascular endothelial growth factor (VEGF) levels in plasma and urine, changes in MVD, changes in VEGF receptor-2 phosphorylation in tumor, and/or changes in ERK 1/2 phosphorylation in stimulated lymphocytes and tumor. OUTLINE: This is a non-randomized, open-label, multicenter study. Patients receive carboplatin IV and paclitaxel IV once on day 1 and oral sorafenib twice daily on days 2-19. Treatment repeats every 21 days for up to 6 courses.\* After 6 courses, patients continue to receive oral sorafenib alone twice daily in the absence of disease progression or unacceptable toxicity. \[Note: \*If sorafenib is discontinued prior to course 6, patients may continue to receive carboplatin and paclitaxel for up to 6 courses; if carboplatin and paclitaxel are discontinued prior to course 6, patients may continue to receive sorafenib alone twice daily on days 1-21 of each course in the absence of disease progression or unacceptable toxicity. \] After completion of study treatment, patients are followed periodically for up to 3 years.

Interventions

DRUGcarboplatin

Given IV

DRUGpaclitaxel

Given IV

DRUGsorafenib tosylate

Given orally

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

Criteria: * Histologically proven uveal melanoma * Must have documented disease progression during or after =\< 1 prior systemic treatment * Measurable disease, defined as \>= 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques or \>= 10 mm by spiral CT scan * No tumor involving major vessels * Zubrod performance status 0-1 * Absolute neutrophil count \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Creatinine =\< 2 times upper limit of normal (ULN) * Bilirubin =\< 2 times ULN * SGOT or SGPT =\< 2 times ULN (5 times ULN if hepatic metastasis present) * INR in range (usually between 2 and 3) * No active bleeding * No bleeding diathesis, active coagulopathy, or pathological condition that carries a high risk of bleeding * No condition (e.g., gastrointestinal tract disease) affecting ability to take oral medication or requiring IV alimentation * Not pregnant or nursing * Fertile patients must use effective contraception * No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for 5 years * At least 28 days since prior systemic treatment for this disease comprising 1 of the following: single chemotherapy agent/regimen; single immunotherapy agent/regimen; single investigational treatment agent/regimen * At least 21 days since prior major surgery * No prior sorafenib or any other agents targeting raf kinase or vascular endothelial growth factor (VEGF) or VEGF receptor * No prior surgical procedures affecting absorption * No concurrent systemic corticosteroid therapy * Topical and/or inhaled steroids are allowed * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John's wort) * No prophylactic granulocyte/platelet colony-stimulating factors during the first course of treatment * Concurrent full-dose oral anticoagulants (e.g., warfarin) are allowed provided all of the following criteria are met: in-range INR ; stable dose of oral anticoagulant; no active bleeding or high risk of bleeding * Stage IV disease * No known varices * No uncontrolled hypertension with systolic blood pressure (BP) \> 140 mm Hg or diastolic BP \> 90 mm Hg * No significant traumatic injury within the past 21 days * No active, uncontrolled peptic ulcer disease

Design outcomes

Primary

MeasureTime frameDescription
Response Rate (Complete and Partial Response)Every 6 weeks for the first 8 cycles of therapy, then every three cycles (9 weeks) until progressionComplete response corresponds to complete disappearance of all measurable and non-measurable lesions with no new lesions. Partial response corresponds to greater than or equal to 30fi decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease.

Secondary

MeasureTime frameDescription
One-year Overall SurvivalEvery 6-9 weeks until progression, after progression every six months for first two years and annually thereafter up to 3 for up to 3 years after registration or until deathMeasured from date of registration to study until death due to any caused with observations last known to be alive censored at the date of last contact
6-month Progression-free SurvivalEvery 6 weeks for the first 8 cycles of therapy, and then every 9 weeks until disease progression for up to 3 years after registration or until deathMeasured from the date of registration to the first of progression or death due to any cause with patients last known to be alive and progression-free censored at the date of last contact
ToxicityWeekly during the first cycle of therapy, then prior to each cycle (one cycle = 3 weeks)Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Countries

United States

Participant flow

Participants by arm

ArmCount
Sorafenib, Carboplatin, Paclitaxel24
Total24

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event3
Overall StudyDid not start treatment1
Overall StudyNot eligible1
Overall StudyOther reason, not protocol specified1

Baseline characteristics

CharacteristicSorafenib, Carboplatin, Paclitaxel
Age, Continuous61 Years
Region of Enrollment
United States
24 participants
Sex: Female, Male
Female
12 Participants
Sex: Female, Male
Male
12 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
23 / 24
serious
Total, serious adverse events
2 / 24

Outcome results

Primary

Response Rate (Complete and Partial Response)

Complete response corresponds to complete disappearance of all measurable and non-measurable lesions with no new lesions. Partial response corresponds to greater than or equal to 30fi decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease.

Time frame: Every 6 weeks for the first 8 cycles of therapy, then every three cycles (9 weeks) until progression

Population: Eligible patients who received some treatment

ArmMeasureValue (NUMBER)
Sorafenib, Carboplatin, PaclitaxelResponse Rate (Complete and Partial Response)0 participants
Secondary

6-month Progression-free Survival

Measured from the date of registration to the first of progression or death due to any cause with patients last known to be alive and progression-free censored at the date of last contact

Time frame: Every 6 weeks for the first 8 cycles of therapy, and then every 9 weeks until disease progression for up to 3 years after registration or until death

ArmMeasureValue (NUMBER)
Sorafenib, Carboplatin, Paclitaxel6-month Progression-free Survival29 Percent of population
Secondary

One-year Overall Survival

Measured from date of registration to study until death due to any caused with observations last known to be alive censored at the date of last contact

Time frame: Every 6-9 weeks until progression, after progression every six months for first two years and annually thereafter up to 3 for up to 3 years after registration or until death

Population: Eligible patients who received some treatment

ArmMeasureValue (NUMBER)
Sorafenib, Carboplatin, PaclitaxelOne-year Overall Survival42 Percentage of population
Secondary

Toxicity

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Time frame: Weekly during the first cycle of therapy, then prior to each cycle (one cycle = 3 weeks)

Population: Eligible patients who started therapy

ArmMeasureGroupValue (NUMBER)
Sorafenib, Carboplatin, PaclitaxelToxicityVision-blurred vision1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityCalcium, serum-low (hypocalcemia)1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityCataract1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityDiarrhea2 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityFatigue (asthenia, lethargy, malaise)1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityFebrile neutropenia1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityHemoglobin2 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityInfec w/ Gr 3/4 neut-Urinary tract1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityLeukocytes (total WBC)4 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityLymphopenia2 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityMucositis/stomatitis (func/symp) - Pharynx1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityNeuropathy: sensory2 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityNeutrophils/granulocytes (ANC/AGC)10 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityPlatelets4 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityPruritus/itching1 Participants with a given type of AE
Sorafenib, Carboplatin, PaclitaxelToxicityRash/desquamation5 Participants with a given type of AE

Source: ClinicalTrials.gov · Data processed: Mar 25, 2026