A Two Arm Trial of Axitinib and Carboplatin/Paclitaxel in Melanoma (CC# 10852)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Adil Daud, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01174238
First received: July 28, 2010
Last updated: December 11, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: Axitinib
Drug: Carboplatin
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Arm Phase II Trial of Sequential Axitinib and Carboplatin/Paclitaxel in Melanoma With Correlative FLT PET Scans (3'Deoxy-3'-18F-Fluorothymidine Positron Emission Tomography Scans)(CC# 10852)

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • To determine the Objective Response Rate (ORR) of axitinib + carboplatin/paclitaxel in metastatic melanoma. [ Time Frame: The primary outcome measure will be assessed by radiographic response using RECIST criteria during every 21 day cycle of treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the resumption of DNA synthesis following axitinib therapy using FLT PET as a radiological biomarker. [ Time Frame: The primary outcome measure will be assessed by radiographic response using RECIST criteria during every 21 day cycle of treatment. ] [ Designated as safety issue: No ]
  • To determine the toxicity profile of this combination of treatment in metastatic melanoma. [ Time Frame: This secondary outcome measure will be determined during 21 day cycles of treatment. ] [ Designated as safety issue: Yes ]
  • To determine the Overall Survival (OS) and Time to Progression (TTP) of patients treated with this regimen. [ Time Frame: These outcome measures will be assessed beginning within 7 days of odd cycles after cycle 1 for the duration of treatment. ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: July 2010
Study Completion Date: December 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
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
5mg BID Axitinib Days 1-14 for dual therapy - 5mg BID QD for patients on monotherapy
Drug: Carboplatin
Day 1 of each 21 day cycle in combination with paclitaxel if patients are in dual therapy phase
Drug: Paclitaxel
Day 1 of each 21 Day cycle in combination with Carboplatin if patients on on dual therapy phase.
Active Comparator: Arm B
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
5mg BID Axitinib Days 1-14 for dual therapy - 5mg BID QD for patients on monotherapy
Drug: Carboplatin
Day 1 of each 21 day cycle in combination with paclitaxel if patients are in dual therapy phase
Drug: Paclitaxel
Day 1 of each 21 Day cycle in combination with Carboplatin if patients on on dual therapy phase.

Detailed Description:

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 (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 and dose will be the same in either cohort, with the exception of the FLT PET scans. We are enrolling only 6 patients to Arm A, the FLT-PET cohort, because of study financial considerations.

Patients will be enrolled in Arm A first, the FLT-PET cohort, to accommodate the radiological manufacture of the FLT-PET scan dye. It is expensive to manufacture and it is not usable forever. However if a patient is unable to participate in Arm A because of logistical issues, i.e. not being able to travel to UCSF for FLT-PET scans we will offer them participation in Arm B so that they can receive treatment that is not available off study.

Each treatment cycle will last for 21days. During Cycle 1, patients will be treated with:

Days 1-14: axitinib 5 mg PO twice daily Days 15-21: break from treatment

In all cycles after Cycle 1, patients will be treated with:

Day 1: paclitaxel 175 mg/m2 over 3 hours followed by carboplatin AUC 5 (AUC 5 is a term used to describe the dosing of carboplatin based on a patient's height, weight and kidney function) over 45 minutes Days 1-14: axitinib 5 mg PO twice daily Days 15-21: break from treatment Arm A: FLT PET cohort subjects will have FLT PET scans up to 2 weeks prior to day 1 and on days 14, 17, and 21 of cycle 1.

Arm B: Treatment-only patients will receive administration of axitinib and carboplatin/paclitaxel on the same schedule and dose as Arm A but will not have FLT PET scans. Patients in Arm B will have standard tumor assessment with FDG PET-CT scans (F18-deoxyglucose positron emission tomography scans), CT Scans, and MRI's.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically proven melanoma with Stage IV or unresectable stage III disease.
  2. Male or female, age ≥ 18 years.
  3. Resolution of all acute toxic effects of prior radiotherapy, chemotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
  4. May have ≤ 2 prior chemotherapy treatments and any prior immunotherapy treatments. These can include dacarbazine and/or temozolomide but not carboplatin or paclitaxel.
  5. 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.
  6. 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.
  7. Adequate organ function as defined by the following criteria:

    1. 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
    2. Total serum bilirubin ≤ 1.5 x ULN (Grade 0-1)
    3. Absolute neutrophil count (ANC) ≥ 1500 /ml
    4. Platelets ≥ 100,000/mL
    5. Hemoglobin ≥ 9.0 g/dL (may be transfused or erythropoietin treated)
    6. Serum calcium ≥12.0 mg/dL
    7. Serum creatinine ≤ 1.5 x ULN
  8. Patients with CNS (central nervous system) metastasis must have had either:

    1. Resected CNS metastasis without evidence of recurrence for > 12 weeks, OR
    2. Brain metastasis treated by stereotactic radiosurgery without evidence of recurrence or progression for 12 weeks, OR
    3. Multiple brain lesions treated with whole brain radiation therapy with stable disease off corticosteroids for at least 12 weeks prior to the start of therapy, AND
    4. Without any evidence of leptomeningeal disease, AND
    5. Patients must be neurologically intact.
  9. May have previous adjuvant therapy with interferon, vaccines, or therapy with IL-2 or GM-CSF.
  10. Measurable disease by RECIST criteria.
  11. ECOG performance status 0 or 1.

Exclusion Criteria:

  1. Major surgery within 4 weeks of starting the study treatment.
  2. 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.
  3. NCI CTCAE version 4.0 grade 2 or greater hemorrhage within 4 weeks of starting study treatment.
  4. History of hemoptysis or bleeding from GI tract.
  5. History of abdominal fistulae or perforation within 6 months prior to starting study treatment.
  6. History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease on screening CT or MRI scan.
  7. 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.
  8. Hypertension that cannot be controlled by medications.
  9. 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).
  10. 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).
  11. 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.
  12. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
  13. CNS disease on stable dexamethasone
  14. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection
  15. 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.
  16. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01174238

Locations
United States, California
Cutaneous Onocology Group at the Helen Dillar Family Comprehensive Cancer Center UCSF
San Francisco, California, United States, 94115
Sponsors and Collaborators
Adil Daud
Investigators
Principal Investigator: Adil Daud, MD Cutaneous Oncology Group at the Helen Dillar Family Comprehensive Cancer Center at UCSF
  More Information

No publications provided

Responsible Party: Adil Daud, Clinical Professor, Hem/Onc, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01174238     History of Changes
Other Study ID Numbers: 10852
Study First Received: July 28, 2010
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Melanoma
Axitinib
Carboplatin
Paclitaxel

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Paclitaxel
Carboplatin
Axitinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014