A Two Arm Trial of Axitinib and Carboplatin/Paclitaxel in Melanoma

NCT01174238 | Completed Phase 2 Results DMC

• 1 other identifier: 10852
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two arm prospective Phase II pilot trial designed to determine the optimal duration of break between axitinib and chemotherapy with carboplatin/paclitaxel in melanoma. In this study, 6 patients will be enrolled to Arm A, the FLT PET scan (3'deoxy-3'-18F-Fluorothymidine positron emission tomography scans)cohort. 30 patients will be enrolled to Arm B, the treatment-only cohort. 36 total patients will be enrolled. The treatment schedule will be the same in either cohort, with the exception of the FLT PET scans.

Conditions

Melanoma

Keywords

Melanoma; Axitinib; Carboplatin; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients with tumor size reduction, i.e. the sum of partial responses plus complete responses. Radiographic response was evaluated using RECIST criteria during every 21-day cycle of treatment.

  Monthly during study treatment, up to 12 months

Secondary Outcomes (4)

• Optimal Interval Between the End of Axitinib Therapy and Initiation of Chemotherapy

  Days 1, 14, 17, and 20 of cycle 1

• Overall Survival (OS)

  Baseline until death or up to 24 months

• Time to Progression (TTP)

  within 7 days of odd cycles after cycle 1 for the duration of treatment, up to 12 cycles

• Increase From Nadir in the Sum of Maximum (18)F-FLT Uptake Values After Treatment Holiday

  Baseline, Day 14, Day 20

Study Arms (2)

Arm A

EXPERIMENTAL

Patients enrolled in Arm A and Arm B will receive the same treatment with study drugs axitinib, carboplatin, and paclitaxel. Patients enrolled in Arm A and Arm B will have tumor imaging assessments: PET-CT, CT Scan, and/or MRI. In addition patients enrolled in Arm A will also have FLT-PET scans.

Drug: Axitinib; Drug: Carboplatin; Drug: Paclitaxel

Arm B

EXPERIMENTAL

Patients enrolled in Arm A and Arm B will receive the same treatment with study drugs axitinib, carboplatin, and paclitaxel. Patients enrolled in Arm A and Arm B will have tumor imaging assessments: PET-CT, CT Scan, and/or MRI. Patients enrolled in Arm B will not have FLT-PET scans.

Drug: Axitinib; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Axitinib DRUG

5mg BID Axitinib Days 1-14 for dual therapy - 5mg BID QD for patients on monotherapy

Arm A; Arm B

Carboplatin DRUG

Day 1 of each 21 day cycle in combination with paclitaxel if patients are in dual therapy phase

Arm A; Arm B

Paclitaxel DRUG

Day 1 of each 21 Day cycle in combination with Carboplatin if patients on on dual therapy phase.

Arm A; Arm B

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 proven melanoma with Stage IV or unresectable stage III disease.
• Male or female, age ≥ 18 years.
• Resolution of all acute toxic effects of prior radiotherapy, chemotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
• May have ≤ 2 prior chemotherapy treatments and any prior immunotherapy treatments. These can include dacarbazine and/or temozolomide but not carboplatin or paclitaxel.
• At least 2 weeks since the end of prior systemic treatment (4 weeks for bevacizumab-containing regimens), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 4.0 grade ≤ 1 or back to baseline except for alopecia or hypothyroidism.
• No evidence of preexisting uncontrolled hypertension. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
• Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin ≤ 1.5 x ULN (Grade 0-1)
• Absolute neutrophil count (ANC) ≥ 1500 /ml
• Platelets ≥ 100,000/mL
• Hemoglobin ≥ 9.0 g/dL (may be transfused or erythropoietin treated)
• Serum calcium ≥12.0 mg/dL
• Serum creatinine ≤ 1.5 x ULN
• Patients with CNS (central nervous system) metastasis must have had either:

You may not qualify if:

• Major surgery within 4 weeks of starting the study treatment.
• Radiation therapy within 2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• NCI CTCAE version 4.0 grade 2 or greater hemorrhage within 4 weeks of starting study treatment.
• History of hemoptysis or bleeding from GI tract.
• History of abdominal fistulae or perforation within 6 months prior to starting study treatment.
• History of or known carcinomatous meningitis, or evidence of symptomatic 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.
• Hypertension that cannot be controlled by medications.
• Current use or anticipated need for treatment with drugs that are known potent CYP3A inhibitors (grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).
• Current use or anticipated need for treatment with drugs that are known potent CYP3A or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
• Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
• Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
• CNS disease on stable dexamethasone
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
• Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.

Sponsors & Collaborators

• Adil Daud: lead

Study Sites (1)

Cutaneous Onocology Group at the Helen Dillar Family Comprehensive Cancer Center UCSF

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Axitinib; Carboplatin; 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)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Adil Daud, MD
• Organization: University of California, San Francisco

adaud@medicine.ucsf.edu

415-353-7392

Study Officials

• Adil Daud, MD

  Cutaneous Oncology Group at the Helen Dillar Family Comprehensive Cancer Center at UCSF

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor, Hem/Onc

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: August 3, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: December 1, 2013
• Last Updated: June 8, 2018
• Results First Posted: June 8, 2018

Record last verified: 2018-05

Locations

US (1)