Clinical Trials

Depression is common in patients with advanced cancer.  Current antidepressants, while effective, have an onset of action of at least several weeks.  Ketamine has emerged as a drug with promise for cancer patients.  It has been shown to potentiate opiate analgesic effects.  Single dose parenteral and enteral administration studies in medically healthy treatment-resistant depressed patients have shown rapid relief of symptoms.  A recent two patient case series reported a rapid and moderately sustained symptom reduction in depression and anxiety in palliative care patients following a single dose of oral ketamine 0.5 mg/kg, with no adverse effects.  Benefit was seen as little as 1 hour after the administration and sustained up to 30 days.  These case reports generate hypotheses of efficacy for ketamine in the treatment of depression and anxiety in patients with advanced cancer.  This study is a randomized, double-blind, placebo-controlled investigation of these hypotheses.

OBJECTIVES:

     Primary

       -  To compare the efficacy of two home-based sleep interventions as therapy for sleep-wake disturbances,as measured by sleep latency or time to fall back asleep after initial sleep onset per sleep diaries, at baseline (week 1) and at the end of week 7 in cancer survivors.

     Secondary

       -  To compare the efficacy of these interventions as therapy for sleep-wake disturbances as measured by the number of awakenings after sleep, sleep quality, sleep difficulty, and sleep latency at baseline (week 1) and weeks 4 and 7 in these participants.

       -  To compare the efficacy of these interventions as therapy for sleep-wake disturbances as measured by the percentage of participants in each group who show improved sleep per the Pittsburgh Sleep Quality Index.

       -  To compare the effects of these interventions on fatigue, mood disturbance, sleep, benefit, and distress in this patient population.

       -  To describe the side effects associated with these interventions in these patients.

       -  To describe patient practice habits and adherence measured via a practice diary.

       -  To explore symptom clusters in this patient population and look at distress as a mediating variable. (Exploratory)

       -  To explore predictors of sleep quality. (Exploratory)

     OUTLINE: This is a multicenter study. Patients are stratified according to current (≥ 1 per week in the past 4 weeks) pharmacological treatment, including anxiolytics, for insomnia or mood (yes vs no), current pharmacologic treatment for pain (yes vs no), sleep difficulty period (≤ 1 month vs > 1 month), and age (≤ 50 vs 51-70 vs > 70 years). Patients are randomized to 1 of 2 intervention groups.

       -  Group 1: Participants receive a home-based sleep intervention comprising a Sleep Hygiene Education booklet, printed stimulus-control guidelines, instructions on sleeping restrictions, and a guided-imagery pre-recorded mp3 device. Participants meet with study personnel for intervention refinement and are asked to practice behaviors consistent with the stimulus-control sheet, to read the sleep hygiene booklet one chapter per day for 7 days during the first week, and then as needed during study. They are also instructed to use the CD, with or without headphones, in a quiet and comfortable place without lights for up to 30 minutes every day for 6 weeks before bedtime. Participants are instructed to go to sleep and wake at the same time every day during study intervention.

       -  Group 2: Participants receive a home-based sleep intervention comprising a Sleep Hygiene Education booklet, printed stimulus-control guidelines, and a pre-recorded mp3 device containing short stories and essays. Participants meet with study personnel and are instructed to practice behaviors consistent with the stimulus control sheet, to read the sleep hygiene booklet, and use the CD as in group 1. Participants are not instructed about sleeping restrictions. They are offered the guided-imagery CD after study completion.

     Patients complete a Three-Day Sleep Diary for 3 consecutive days at baseline and during weeks 4 and 7 of study intervention. Patients also complete questionnaires on Numeric Analog Sleep for Pain Scale, daily use of CD, Sleep Hygiene Practice, Pittsburgh Sleep Quality Index, Profile of Mood States, Brief Fatigue Inventory, Distress Thermometer, Side-Effect Questionnaire, and a Subject Global Impression of Change at baseline, during weeks 2 and 6, and after completion of study intervention.

-  Hypothesis:

          - Direct CGN enhances neurolytic drug delivery into celiac ganglia and increases the efficacy of neurolysis and subsequent pain control and survival in patients with pancreatic carcinoma.

       -  Rationale:

            -  Standard CPN leads to inaccurate delivery of the injectate with rapid dispersal thereby only briefly remaining in contact with neural structures and limiting the degree of neurolysis. Poor targeting and delivery of a neurolytic agent may result in diminished neurolysis and decrease efficacy.

OBJECTIVES:

     Primary

       -  To determine if topically administered supersaturated calcium phosphate (Caphosol), rinsed orally four times daily at the initiation of conditioning for hematopoietic stem cell transplantation (HSCT), reduces oral mucositis as demonstrated by a decrease in duration of severe oral mucositis (World Health Organization [WHO] Grade 3 or 4), compared to placebo.

     Secondary

       -  To determine whether Caphosol administration, when compared to placebo, reduces oral mucositis as demonstrated by a decrease in incidence of severe oral mucositis (WHO Grade 3 or 4); severity of mucositis according to mouth pain categorical rating scale and Oral Mucositis Daily Questionnaire (OMDQ); incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents); and incidence and duration of total parenteral nutrition (TPN) administration.

       -  To determine whether Caphosol administration, when compared to placebo, reduces the incidence of febrile neutropenia and invasive bacterial infections.

       -  To validate a new pediatric measure of oral mucositis termed the Children's International Mucositis Evaluation Scale (ChIMES).

     OUTLINE: This is a multicenter study. Patients are stratified according to conditioning regimen (total-body irradiation [TBI] or melphalan vs neither TBI nor melphalan) and hematopoietic stem cell transplantation (HSCT) (autologous vs allogeneic). Patients are randomized to 1 of 2 treatment arms.

       -  Arm I: Patients rinse and gargle with supersaturated calcium phosphate rinse over 1 minute four* times daily beginning on the first day (about day -7) of the conditioning regimen.

       -  Arm II: Patients rinse and gargle with placebo over 1 minute four* times daily beginning the first day (about day -7) of the conditioning regimen.

       -  NOTE: * Patients who reach WHO grade 3 or 4 mucositis have the option to request a total of 6 rinses daily.

     In both arms, treatment continues until day 20 post-transplantation OR until mucositis resolves to WHO Grade ≤ 2 for two consecutive days OR on day 12 in patients who do not experience oral mucositis of at least WHO Grade ≥ 1.

     Patients are assessed daily by trained healthcare professionals using the Oral Mucositis Daily Questionnaire (OMDQ), the Pain Rating Scale, the WHO Mucositis Scale, and the Children's International Mucositis Evaluation Scale (ChIMES) from day -1 and continuing until day 20. Patients are also observed for the incidence of total dose and duration of parenteral opioid analgesic use, duration of total parenteral nutrition (TPN) administration, febrile neutropenia, and invasive bacterial infections.

     After completion of study therapy, patients are followed up for 30 days.

PRIMARY OBJECTIVES:

     I. To explore whether venlafaxine can prevent or ameliorate chronic, cumulative neurotoxicity associated with oxaliplatin in cancer patients receiving oxaliplatin, fluorouracil, leucovorin calcium (FOLFOX).

     SECONDARY OBJECTIVES:

     I. To explore whether venlafaxine can ameliorate acute neuropathy associated with oxaliplatin.

     TERTIARY OBJECTIVES:

     I. To explore whether venlafaxine can increase the cumulative oxaliplatin doses that can be delivered without dose-limiting chronic neurotoxicity.

     II. To explore whether venlafaxine causes adverse events in this setting. III. To explore whether the neuropathy data provided by the Rydel-Seiffer graduated tuning fork is consistent with patient-reported outcome (PRO) measures of chemotherapy-induced peripheral neuropathy (CIPN) and whether this tool might cause different results in patients receiving venlafaxine versus placebo.

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

     ARM I: Patients receive venlafaxine orally (PO) twice daily (BID) beginning on day 1 of and continuing through completion of FOLFOX.

     ARM II: Patients receive placebo PO BID beginning on day 1 of and continuing through completion of FOLFOX.

     After completion of study treatment, patients are followed up at 1, 3, 6, 12, and 18 months.

PRIMARY OBJECTIVES:

     I. To assess the safety and feasibility of short-term fasting prior to administration of chemotherapy.

     SECONDARY OBJECTIVES:

     I. To evaluate weight changes in patients who are exposed to short-term fasting prior to chemotherapy.

     II. To get a preliminary estimate of the longest feasible fasting period prior to chemotherapy.

     III. To evaluate the toxicity profile of systemic chemotherapy treatment in patients who undergo short-term fasting prior to treatment.

     IV. To investigate changes in plasma glucose, insulin, IGF-1 and IGF-1BP in patients who undertake short-term fasting.

     OUTLINE:

     COHORT I: Patients fast 24 hours before day 1 of course 2 of chemotherapy. If fast is well tolerated, patients may escalate fasting by 12 hours for each subsequent course of chemotherapy for up to 3 courses in the absence of unacceptable toxicity.

     COHORT II: Patients fast at the longest fasting regimen found to be safe and tolerable in cohort I before day 1 of each course of course of chemotherapy for up to 4 courses in the absence of unacceptable toxicity.

Severe nausea and/or vomiting in patients receiving radiotherapy to the upper abdomen is common despite having received pre-medication with ondansetron, a standard preventive treatment. This study aims to reduce the incidence of significant nausea and/or vomiting with the addition of the NK1-antagonist aprepitant to standard ondansetron treatment. This study will also assess the safety and tolerability of prolonged administration of aprepitant over the 4 to 6 week period of radiation treatment.

PRIMARY OBJECTIVES:   I. To obtain pilot data regarding the possible effect of pregabalin on pain related to paclitaxel-associated acute pain syndrome (P-APS).    SECONDARY OBJECTIVES: I. To obtain pilot data regarding the possible effect of pregabalin on paclitaxel-induced peripheral neuropathy.  II. To obtain pilot data regarding the possible relative toxicities related to pregabalin therapy in this study situation.    TERTIARY OBJECTIVES:   I. To characterize neurological testing abnormalities that might occur with the P-APS, and to evaluate neurological testing abnormalities during the period of the longer-term chemotherapy-induced peripheral neuropathy (CIPN).  II. To determine the PRO incidence and characteristics of, and change in, P-APS and paclitaxel induced more chronic CIPN over several cycles. These data will serve to confirm the results obtained in our previous natural history study N08C1.    OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive pregabalin orally (PO) twice daily (BID), beginning on the first night of chemotherapy, for 12 weeks and then once daily (QD) for 1 week.      ARM II: Patients receive placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.    After completion of study treatment, patients are followed up every 30 days for 6 months.

OBJECTIVES:

     I. To record the types of patients that we treat, along with the reported efficacy and potential toxicity associated with scrambler therapy.

     II. To get experience with patient reported outcome measurement tools that we use in this trial, including a report of analgesic use.

     OUTLINE:    Patients undergo scrambler therapy for 30 minutes daily for up to 10 consecutive days. Treatment continues in the absence of unacceptable toxicity.    After completion of study treatment, patients are followed up for 10 weeks.

     III. To explore neurologic testing changes in patients receiving scrambler therapy.