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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01014351
Recruitment Status : Completed
First Posted : November 17, 2009
Results First Posted : March 26, 2014
Last Update Posted : March 26, 2014
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

November 16, 2009
November 17, 2009
February 10, 2014
March 26, 2014
March 26, 2014
February 2010
February 2012   (Final data collection date for primary outcome measure)
Progression-free Survival (PFS) [ Time Frame: 18 months ]
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.
To evaluate the progression-free survival (PFS) of patients with metastatic melanoma treated with the combination of everolimus, paclitaxel, and carboplatin [ Time Frame: 18 months ]
Complete list of historical versions of study NCT01014351 on Archive Site
  • Overall Survival (OS) [ Time Frame: 18 months ]
    Overall survival (OS) is defined as the time from randomization until death from any cause.
  • Objective Response Rate (ORR) [ Time Frame: 18 months ]
    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.
  • To determine the response rate, disease control rate, and overall survival of patients with metastatic melanoma treated with everolimus, paclitaxel, and carboplatin [ Time Frame: 18 months ]
  • To determine the toxicity profile of the combination of everolimus, paclitaxel, and carboplatin in this patient population [ Time Frame: 18 months ]
  • To correlate immunohistochemical tissue microarray with response rates, PFS, and overall survival [ Time Frame: 18 months ]
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Study of Everolimus With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
A Phase II Study of Everolimus in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma
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.
Not Provided
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Metastatic Melanoma
  • Drug: Paclitaxel
    Paclitaxel, 175mg/m2 by IV infusion over 1-3 hours on day 1 of every 21 day cycle
    Other Name: Taxol
  • Drug: Carboplatin
    Carboplatin, AUC 6 given by IV infusion over 20-30 minutes on day 1 of every 21 day cycle
    Other Name: Paraplatin
  • Drug: Everolimus
    Everolimus, 5 mg by mouth (PO) once a day, continuous dosing every 21-day cycle
    Other Names:
    • RAD001
    • Afinitor
Experimental: Paclitaxel/Carboplatin/Everolimus
Systemic Therapy using everolimus, paclitaxel and carboplatin given during a 21-day treatment cycle
  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Drug: Everolimus
Hauke RJ, Infante JR, Rubin MS, Shih KC, Arrowsmith ER, Hainsworth JD. Everolimus in combination with paclitaxel and carboplatin in patients with metastatic melanoma: a phase II trial of the Sarah Cannon Research Institute Oncology Research Consortium. Melanoma Res. 2013 Dec;23(6):468-73. doi: 10.1097/CMR.0000000000000014.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
August 2013
February 2012   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
Study Chair: John D. Hainsworth, M.D. SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP