Study of Everolimus With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01014351
First received: November 16, 2009
Last updated: February 10, 2014
Last verified: January 2014
  Purpose

Based on data demonstrating synergy between paclitaxel and mammalian target of rapamycin (mTOR) inhibition, the investigators propose that the addition of everolimus to paclitaxel with carboplatin should lead to improvements in efficacy as measured by progression-free survival and response rate.


Condition Intervention Phase
Metastatic Melanoma
Drug: Paclitaxel
Drug: Carboplatin
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Everolimus in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the time from randomization until objective tumor progression (PD) or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time from randomization until death from any cause.

  • Objective Response Rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Objective Response Rate (ORR) is defined as the Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.


Enrollment: 70
Study Start Date: February 2010
Study Completion Date: August 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel/Carboplatin/Everolimus
Systemic Therapy using everolimus, paclitaxel and carboplatin given during a 21-day treatment cycle
Drug: Paclitaxel
Paclitaxel, 175mg/m2 by IV infusion over 1-3 hours on day 1 of every 21 day cycle
Other Names:
  • Paclitaxel
  • Taxol
Drug: Carboplatin
Carboplatin, AUC 6 given by IV infusion over 20-30 minutes on day 1 of every 21 day cycle
Other Names:
  • Carboplatin
  • Paraplatin
Drug: Everolimus
Everolimus, 5 mg by mouth (PO) once a day, continuous dosing every 21-day cycle
Other Names:
  • Everolimus
  • RAD001
  • Afinitor

  Eligibility

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

Inclusion Criteria:

  1. Histologically confirmed metastatic melanoma.
  2. Stage III or IV disease that is not amenable to resection.
  3. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the patient has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation.
  4. ECOG Performance Status of 0 or 1.
  5. Life expectancy ≥12 weeks.
  6. No prior cytotoxic chemotherapy or targeted therapy. Immunotherapy is allowed (i.e., interleukin-2 or interferon).
  7. Adequate hematological function:

    • absolute neutrophil count (ANC) ≥1500/µL and
    • platelets ≥100,000/µL and
    • hemoglobin >9 g/dL
  8. Adequate renal function: serum creatinine ≤2.0 mg/dL or calculated (measured) GFR ≥50 mL/min.
  9. Adequate hepatic function:

    • serum bilirubin ≤1.5 x institutional upper limit of normal (ULN);
    • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or ≤5 × ULN in patients with documented liver metastases.
  10. Normal PT, INR. Patients on coumadin anticoagulation are eligible if they are on a stable dose, with an INR in the therapeutic range.
  11. Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can be included after initiation of appropriate lipid lowering medication.
  12. Age ≥18 years.
  13. Ability to swallow whole pills.
  14. Patient must be accessible for treatment and follow-up.
  15. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion Criteria:

  1. Previous treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus), paclitaxel, or carboplatin.
  2. Treatment with any investigational agent ≤4 weeks of protocol treatment.
  3. Patients currently receiving anticancer therapies or who have received anticancer therapies ≤3 weeks of the start of the study drug (including radiation therapy, immunotherapy).
  4. Patients, who have had a major surgery or significant traumatic injury ≤4 weeks of start of study drug or patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
  5. Patients receiving chronic, systemic treatment with corticosteroids (dose >10 mg daily of methylprednisolone or equivalent) or other immunosuppressive agents. Topical or inhaled steroids are allowed.
  6. Immunization with attenuated live vaccine ≤1 week of study or anytime during study treatment period.
  7. Patients with active brain metastases are ineligible. Patients with treated brain metastases are eligible if (1) radiation therapy was completed ≥4 weeks prior to study entry; (2) surgery was completed ≥4 weeks prior to study entry; (3) follow-up scan shows no disease progression; and (4) patient does not require steroids.
  8. Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:

    • severely impaired lung function defined as a DLCO ≤50% of the normal predicted value and/or O2 saturation ≤88% at rest on room air.
    • symptomatic congestive heart failure of New York Heart Association Class III or IV.
    • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant disease.
    • uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN.
    • active (acute or chronic) uncontrolled severe infections.
    • liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
  9. Active, bleeding diathesis.
  10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  11. A known history of human immunodeficiency virus (HIV) seropositivity.
  12. Known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
  13. Use of St. John's Wort is prohibited. Drugs or substances (e.g., grapefruits, star fruits, seville oranges, and their juices and products), known to be inhibitors or inducers of the isoenzyme CYP3A4 should be avoided. Co-administration with substrates, inducers, or inhibitors of P glycoprotein should also be avoided.
  14. Female patients who are pregnant or breastfeeding or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential [WOCBP] must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus.) WOCBP should continue to use effective contraception for 8 weeks after ending everolimus treatment.
  15. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
  16. History of noncompliance to medical regimens. Patients unwilling to, or unable to, comply with the protocol.
  17. History of any other disease, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or a condition that may render the patient at high risk for treatment complications using these agents.
  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: NCT01014351

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Indiana
Oncology Hematology of SW Indiana
Evansville, Indiana, United States, 47630
United States, Louisiana
Hematology Oncology Clinic, LLP
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Michigan
Grand Rapids Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Nebraska
Nebraska Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
United States, Virginia
Peninsula Cancer Institute
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
SCRI Development Innovations, LLC
Novartis
Investigators
Study Chair: John D. Hainsworth, M.D. SCRI Development Innovations, LLC
  More Information

Additional Information:
Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01014351     History of Changes
Other Study ID Numbers: SCRI MEL 19
Study First Received: November 16, 2009
Results First Received: February 10, 2014
Last Updated: February 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Metastatic Melanoma
Everolimus
Paclitaxel
Carboplatin

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
Sirolimus
Everolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on September 16, 2014