Clinical Trials

This multicenter, randomized, double-blind, placebo-controlled phase 3 study will evaluate the safety and efficacy of vemurafenib alone and vemurafenib in combination with GDC-0973, a MEK inhibitor, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma. Patients will be randomized to one of two treatment arms, Arm A: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and placebo (days 1-21 of each cycle); Arm B: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and GDC-0973 60 mg once daily (days 1-21 of each cycle). Patients will receive treatment until disease progression, unacceptable toxicity or withdrawal of consent.

OBJECTIVES:

     Primary

       -  To assess whether there is sufficient promise of an impact of the addition of everolimus to the combination of carboplatin, paclitaxel, and bevacizumab on progression-free survival that it would be recommended for further testing in patients with metastatic malignant melanoma.

     Secondary

       -  Estimate the confirmed tumor response rate in patients treated with carboplatin, paclitaxel, and bevacizumab with or without everolimus.

       -  Estimate the distribution of overall survival time in patients treated with these regimens.

       -  Assess the safety profile of these regimens in these patients.

       -  Examine the impact of therapy on angiogenesis and immune homeostasis.

       -  Assess common genetic variants in mTOR and associated genes that may impact response to therapy.

       -  Collect circulating tumor cells in a valid and reproducible way and assess target marker expression using immunofluorescence and reverse transcriptase-PCR.

     OUTLINE: This is a multicenter study. Patients are stratified according to elevated LDH (above upper limit of normal) at baseline (yes vs no), location of metastatic disease (M1a [skin, subcutaneous tissue, or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and prior chemotherapy for metastatic disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

       -  Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel IV over 60 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

       -  Arm II: Patients receive bevacizumab, paclitaxel, and carboplatin as in arm I. Patients also receive oral everolimus on 3 days a week. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

     Blood samples are collected at baseline and periodically during study for analysis of plasma VEGF levels by ELISA; changes in immune homeostasis by immunophenotyping, tetramer assay, and ELISPOT assay; and analysis of genetic variants in mTOR and associated genes by polymorphism studies.

     After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

OBJECTIVES: - To collect clinical history, family history, and blood and/or tissue samples from family members of patients diagnosed with pancreatic diseases, pancreatic cancer, or melanoma. - To learn whether inherited factors increase the risk of pancreatic diseases, pancreatic cancer, or other cancers. OUTLINE: Study participants undergo collection of blood and/or tissue samples as well as survey data for inclusion in a familial data and tissue registry. Participants complete two baseline surveys regarding their personal, family, health, and environmental exposure histories and regarding their opinions on cancer and cancer screening. Patients also complete a follow-up survey at 1 year and undergo review of their medical records.

This study is a multi-center, Phase 1 clinical trial to determine the safety and feasibility of minimally invasive inguinal lymph node dissection for patients with melanoma. Licensed surgeons who have undergone special training, including a course at the Mayo Clinic Rochester in minimally invasive lymph node dissection (MILND) will perform the new procedure at their home institutions. The study will characterize the learning curve of MILND in the clinical setting, and evaluate the safety of the new operative technique.

     The hypotheses for this study are: 1) minimally invasive groin dissection is a safe procedure. 2) a structured educational training program is a feasible and effective method to train practicing surgeons in this novel procedure and 3) pre-course generic laparoscopic technical skills correlate with minimally invasive superficial groin dissection performance in a clinical setting, including operative oncologic standards and safety metrics.

PRIMARY OBJECTIVES:

     I. To evaluate recurrence-free survival (RFS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (high dose ipilimumab; HIP) or 3 mg/kg (low dose ipilimumab: LIP) versus those randomized to receive HDI utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant).

     II. To evaluate overall survival (OS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (HIP) or 3 mg/kg (LIP) versus those randomized to receive HDI utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant).

     SECONDARY OBJECTIVES:

     I. To evaluate safety and tolerability of post-operative adjuvant ipilimumab therapy given at either 10 mg/kg (HIP) or 3 mg/kg (LIP).

     II. Among patients enrolled by CCOPs, to compare the global QOL between the ipilimumab arms versus HDI using FACT-G form and to evaluate the effect of treatment-related side effects that may have an impact on the health-related domains of QOL using FACIT-D and FACT-BRM.

     OUTLINE: Patients are randomized to 1 of 2 treatment arms.

     ARM I: Patients receive induction ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

     ARM II: Patients receive induction high-dose recombinant interferon alfa-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alfa-2b subcutaneously on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.

     After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 15 years.

The purpose of this study is to determine how safe and how well POL-103A works in preventing the relapse of melanoma after patients who have undergone surgery.