scholarly journals Continuous intravenous vitamin C in the cancer treatment: re-evaluation of a Phase I clinical study

2019 ◽  
Vol 9 (3) ◽  
pp. 180
Author(s):  
Nina Mikirova ◽  
Joseph Casciari ◽  
Ronald Hunninghake
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Vitamin C ◽  
Phase I ◽  
Cancer Patients ◽  
Phase 1 ◽  
Cancer Prognosis ◽  
Sodium Ascorbate ◽  
High Dose ◽  
Treatment Schedule

Background: Intravenous high-dose vitamin C (IVC) therapy is widely used in naturopathic and integrative oncology. A number of Phase I and Phase II clinical trials were launched to prove the benefits of the IVC therapy. Many case studies demonstrated the effectiveness of IVC, with various degrees of success. Clinical trials using IVC to treat cancer have, to date, demonstrated its safety without conclusively proven its efficacy.  One difficulty in administering IVC is determining the optimal treatment schedule.  To this end, data from a previous Phase 1 clinical trial conducted in 1998 using continuous vitamin C infusions was analyzed to examine the effects of this regimen on key prognostic parameters.  Method: Twenty-four subjects were given continuous IVC at doses between 150 and 710 mg/kg/day. Most of the patients had colon cancer with liver and lung metastasis and three patients had pancreatic or liver cancer. All patients had several chemotherapy/radiation treatments before entering the study. Patients were treated by pharmaceutical grade sodium ascorbate diluted in Lactated Ringers solution with the rate of infusion of 20 ml/hr or 10 ml/hr for lower doses. This diluted solution was administered by continuous infusion.Results: Prior to treatment, serum lymphocyte counts and ascorbate concentrations tended to be low while serum levels of lactate dehydrogenase (LDH), neutrophils, and glucose tended to be high.  Improvements were seen during IVC therapy.  In patients with initially elevated neutrophil levels, numbers tended to decrease.  In contrast, increased absolute neutrophil and lymphocyte numbers were seen in patients with initially low counts.  Neutrophil to lymphocyte ratios (NLR) proved to be a good indicator of cancer patients’ survival times (high NLR, low survival).   This was also true of LDH, creatinine, and glucose concentrations.   In patients with the highest pre-treatment NLR, rate of growth of this ratio decreased significantly during therapy.  IVC treatments were also associated with decreases in glucose concentrations, restoration of vitamin C levels, and, in about 40% of cases, reductions in LDH levels. Conclusions: As the result of the study we found that continuous IVC infusions improved several parameters associated with poor cancer prognosis. The data suggests a strategic benefit to using lower IVC doses in continuous infusions: raising the dose above 300 mg/kg/day (20 grams in 70 kg human) increased the frequency of side effects without noticeably increasing plasma ascorbate levels.  Moreover, improvements in lymphocyte counts at low IVC doses tended to decrease at the higher doses.  In conclusion, continuous infusions had benefits to cancer patients and further research in this area is warranted.Keywords: ascorbic acid; continuous infusion; cancer patients; clinical trial; lymphopenia; neutrophil to lymphocyte ratio; hyperglycemia; safety.

scholarly journals Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

2006 ◽  
Vol 24 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Andrew J. Vickers ◽  
Joyce Kuo ◽  
Barrie R. Cassileth
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Phase Ii ◽  
Dose Finding ◽  
Phase Iii ◽  
High Dose ◽  
Free Text ◽  
Phase Ii Trials ◽  
Off Label

Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.

scholarly journals Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblast Derived from Umbilical Cord Mesenchymal Stem Cell for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial

2021 ◽  
Author(s):  
Heejae Won ◽  
Shin-Yoon Kim ◽  
Sunray Lee ◽  
Hyun Sook Park ◽  
Seung-Hoon Baek
Keyword(s):  
Clinical Trial ◽  
Femoral Head ◽  
Phase I ◽  
Umbilical Cord ◽  
Early Stage ◽  
Phase 1 ◽  
High Dose ◽  
Human Umbilical Cord ◽  
Single Center ◽  
Safety And Efficacy

Abstract BackgroundVarious techniques for joint preservation have been attempted in early stage of osteonecrosis of femoral head (ONFH), but the effects are still controversial. Recently, a combination therapy of core decompression (CD) and MSCs collected from bone marrow, adipocytes or human umbilical cord has been introduced, and satisfactory results have been reported. However, there is no study in which human umbilical cord-derived osteoblasts (hUC-O) were administered directly to the lesion in early ONFH. We have classified the location and size of lesions in early-stage ONFH, and will evaluate the hypothesis that the application of hUC-O is a safe and effective treatment.MethodsThis is a prospective, single-center, phase I and open-labeled clinical trial. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 ONFH will be assigned to a low-dose (n = 3, 1 ´ 107 hUC-O cells), medium-dose (n = 3, 2 ´ 107 cells), and high-dose group (n = 3, 4 ´ 107 cells) in the order of their arrival at the facility, and up to 18 patients will be enrolled depending on whether dose limiting toxicity occurs. We will perform CD on the participants, administer hUC-O according to the assigned group, and followed up for 12 weeks, including a total of 5 visits. This study will have 3 aims; first, to evaluate the safety of hUC-O through adverse events assessment, laboratory tests, vital sign assessment, physical examination, and electrocardiogram (ECG) test.; and second, to assess the clinical outcomes after hUC-O application by comparing pain visual analog scale (VAS), Harris Hip scores (HHS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) before and after surgery; and third, to evaluate the radiographic results after hUC-O application by comparing extent of necrotic lesions according to the ARCO and Japanese Investigation Committee (JIC) classification on magnetic resonance imaging.DiscussionThis clinical trial is a pilot phase 1 study evaluating the safety and efficacy of hUC-O local application combined with CD in early-stage ONFH patients. This study will provide the useful information on the treatment with hUC-O for those suffering from ONFH.Trial registration: Clinical Research Information Center (CRIS) established at the Korea Centers for Disease Control and Prevention (KDCA), KCT0006627. Registered 30 September 2021, https://cris.nih.go.kr/cris/search/detailSearch.do/20332

Perception and knowledge of clinical trials and factors affecting participation of regional and rural cancer patients of North Queensland

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17558-e17558
Author(s):  
S. S. Sabesan ◽  
B. Burgher ◽  
S. Varma ◽  
P. Piliouras
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Phase 1 ◽  
Willingness To Participate ◽  
Or Education ◽  
Factors Affecting ◽  
Significant Relationships ◽  
Rural Patients ◽  
Phase I And Ii

e17558 Background: The best treatment option for most cancers is participation in clinical trials. Participation in trials is generally low and among rural patients it is likely to be even lower. The aim of this study was to assess knowledge about and attitudes towards clinical trials among rural and regional cancer patients of North Queensland. Methods: A questionnaire-based survey was conducted in outpatient clinics at the Townsville Cancer Centre on all types of cancer patients. Results: The mean age of the 178 participants was 56 years and 45.4% lived in rural or remote areas. Median distance to the trial centre (Townsville) for rural participants was 180 km (range 80 - 1300 km). Being asked whether they would take part in a RCT, 13.2% of participants said no, 56.3% said yes, and 30.5% were unsure. There were no significant relationships between willingness to participate and rurality (p = 0.896) or education level (p = 0.943). For the majority of patients, the number of clinic visits and blood tests required did not matter. Cost of travel (41.1% rural/remote; 23.5% regional; p < 0.001) and the need for family or friends to accompany (38.9% rural/remote; 24.1% regional; p = 0.021) were more important for rural/remote than regional patients as factors affecting participation. Only 16.4% of participants were aware of early studies. After education, percentage of patients willing to participate in phase I and II studies were 57% and 84%, respectively. Rural patients were less willing to participate in phase I studies than regional patients (33.9% vs 52.6%, p = 0.029). Conclusions: Rural patients are as interested in participating in clinical trials as urban patients except for phase 1 trials and should not be excluded because of rurality. Knowledge of trials is poor and there is a need for education early. Cost of travel seems more important for rural patients and as such budgets should include cost of travel to encourage participation of rural patients. No significant financial relationships to disclose.

Perceptions concerning clinical trials in oncology patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16533-e16533
Author(s):  
Dana Lee ◽  
Ju-Hsien Chao ◽  
Sandy Stevens ◽  
Goetz H. Kloecker
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Treatment Option ◽  
Phase 1 ◽  
Cancer Center ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
Oncology Patients

e16533 Background: Accrual to clinical trials among adult cancer patients is persistently low. Patient preference plays an important role in enrollment. To identify the reasons why patients decline study participation, it is important, to evaluate the perceptions of newly diagnosed oncology patients about clinical trials. Methods: Patients were given a ten-question survey reflective of their attitudes regarding clinical trials as a treatment option at their initial visit. The self-directed questionnaire was scored on an ordinate scale from strongly agree (1) to strongly disagree (5). Results: Ninety-two new patients were surveyed in the cancer - specific multispecialty clinics in an academic cancer center. The patients expected information relating to eligible clinical trials and privacy protection by university sponsored studies as they strongly concurred with “I expect my doctor to inform me about clinical trials that I am eligible for” (mean score 2.15, p=0.001) followed by “all possible measures to protect my privacy are likely to be taken in a clinical trial that is sponsored by a university” (2.36, p=0.36). The strongest disagreement was “If enrolled in a clinical trial, I am comfortable being assigned by a method such as ‘flipping a coin’ or ‘throwing a dice’” (3.73, p=0.001) and “I would be willing to participate in a clinical trial as a first line treatment option” (3.50, p=0.001). Industry sponsored trials, phase 1 trials, second line treatment trials, privacy concerns and investigator initiated trials and time commitment and altruistic reasons did not significantly deviate from the mean preference (2.5) by a one sample T-test analysis. Conclusions: Patients consider the option of clinical trials as important in their treatment, and expect to be informed by their oncologist about clinical trials. Newly diagnosed cancer patients perceive randomization and first line trials negatively. Since randomized data provides new standards for care and hope for improved treatment, patients and their families must be educated about their importance.

Survival and clinical outcomes of ovarian cancer patients enrolled in phase I clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5559-5559
Author(s):  
Bradley Corr ◽  
Marisa Moroney ◽  
Jeanelle Sheeder ◽  
Brandon Sawyer ◽  
S. Gail Eckhardt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Ca 125 ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Heavily Pretreated

5559 Background: Ovarian cancer patients who enroll in Phase I clinical trials are typically platinum resistant, heavily pretreated patients with a poor prognosis. Historically, clinical benefit of Phase I trials in this patient population has been uncertain. We assessed prognostic factors and survival in women with recurrent, previously treated ovarian cancer who enrolled in Phase I clinical trials. Methods: We performed a retrospective analysis of all ovarian cancer patients who were treated on Phase I clinical trials from 2008 through 2018 at the University of Colorado Cancer Center. Patient characteristics, treatment-related toxicities and survival data were assessed. Descriptive statistics and Cox proportional hazards models were utilized to identify risk factors associated with survival time. Results: A total of 132 individual patients were treated on Phase I clinical trials. Patients had a median age of 59 years (range 33-88) with a median of 5.5 (range 1-13) previous chemotherapy lines. 53/132 (40%) of patients were treated on multiple Phase I trials with a median of 1 (range 0-5) prior Phase 1 clinical trial enrollments. All patients had an ECOG performance status of 0 or 1. Overall response rate (defined as complete or partial response) was 9% and disease control rate (defined as complete or partial response or stable disease as best response) was 33%. Median overall survival (OS) was 11.5 months (95% CI: 9.3-13.7). Two patients died on trial due to progression of disease while no patients died due to treatment-related toxicity. In multivariate analysis, independent risk factors predicting shorter survival were elevated CA-125 (HR 2.8; 95% CI: 1.6-5.2) and albumin < 3.5 g/dL (HR 2.5; 95% CI: 1.65-3.79). BMI > 25 predicted longer survival (HR 0.65; 95% CI: 0.44-0.96). Conclusions: Phase I clinical trials for heavily pretreated ovarian cancer patients are safe by a standard of no patients experiencing toxicity-related deaths in our study. They are clinically efficacious with patients experiencing OS of 11.5 months, which is comparable to existing approved therapies. Elevated CA-125 and low albumin levels predict shorter survival, while BMI > 25 predicts longer survival. Phase I clinical trial options should be considered for all heavily pretreated ovarian cancer patients if available to them.

scholarly journals Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial (Preprint)

2018 ◽  
Author(s):  
Jack W Shteamer ◽  
R Donald Harvey ◽  
Boris Spektor ◽  
Kimberly Curseen ◽  
Katherine Egan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Pain ◽  
Phase I ◽  
Cancer Patients ◽  
Preliminary Data ◽  
Initial Step ◽  
Opioid Therapy ◽  
High Dose ◽  
Double Blind ◽  
Patient Reported

BACKGROUND Approximately 12 million Americans are affected with cancer. Of these, 53% experience pain at all stages of cancer. Pain may remain uncontrolled despite high-dose opioid therapy, and opioids have many well-documented harmful side effects. Intranasal ketamine has been shown to be effective in controlling breakthrough noncancer pain in a double-blind randomized control trial (DBRCT) by Carr et al in 2003 as well as to help with depression in a DBRCT by Lapidus et al in 2014. We seek to obtain preliminary data on the safety, feasibility, and utility of this novel technique for the treatment of uncontrolled cancer pain. OBJECTIVE This study aimed to obtain preliminary data via a clinical trial addressing the safety, feasibility, pharmacokinetics, and pharmacodynamics of intranasal ketamine. These initial findings will be applied to a subsequent trial to determine the effectiveness and associated toxicities of ketamine in a larger sample of cancer patients and to address the compelling need to identify new, successful management therapies for cancer pain. METHODS This is an institutional review board– and investigational new drug–approved, prospective phase I/II trial to investigate the safety and use of intranasal ketamine in patients with uncontrolled pain related to cancer or cancer treatment. Informed consent will be obtained prior to all study procedures. All patients will be assigned to the same investigational treatment arm. After patient selection via inclusion/exclusion criteria, patients will be seen over 5 visits, with each visit conducted 2-7 days apart. Patients will be administered ketamine on visits 1-4 and monitored for 240 minutes with continuous pulse oximetry and regular blood pressure checks. Blood samples as well as patient-reported outcomes will be collected at set time points at baseline and after drug delivery. Patients will receive 10 mg intranasal ketamine on visit 1, 10 mg intravenous ketamine on visit 2, 30 mg intranasal ketamine on visit 3, and 50 mg intranasal ketamine on visit 4. On visit 5, an addition blood sample will be drawn. RESULTS As of March 2019, enrollment is in progress, and a total of 7 subjects have completed the study. Enrollment is expected to be completed by April 2019. Final data analysis will commence soon after, and the results are expected to be submitted for publication in 2019. CONCLUSIONS If intranasal ketamine can be utilized for pain control in cancer patients, it could provide superior analgesia and better quality of life, without the risk of significant respiratory depression and constipation associated with opioid medications. These findings will be an important initial step toward testing the effectiveness of intranasal ketamine as a nonopioid medication for cancer pain and as potential maintenance outpatient therapy. CLINICALTRIAL ClinicalTrials.gov NCT03146806; https://clinicaltrials.gov/ct2/show/NCT03146806. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12125

scholarly journals High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0120228 ◽  
Author(s):  
L. John Hoffer ◽  
Line Robitaille ◽  
Robert Zakarian ◽  
David Melnychuk ◽  
Petr Kavan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vitamin C ◽  
Phase I ◽  
Advanced Cancer ◽  
Cytotoxic Chemotherapy ◽  
High Dose ◽  
Intravenous Vitamin

scholarly journals NGlycolylGM3/VSSP Vaccine in Metastatic Breast Cancer Patients: Results of Phase I/IIa Clinical Trial

2012 ◽  
Vol 6 ◽  
pp. BCBCR.S8488
Author(s):  
Ana de la Torre ◽  
Julio Hernandez ◽  
Ramón Ortiz ◽  
Meylán Cepeda ◽  
Kirenia Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Objective Response ◽  
Metastatic Breast ◽  
Treatment Schedule ◽  
Breast Cancer Patients

Patients treated with vaccines based on NGlycolil gangliosides have showed benefit in progression free survival and overall survival. These molecules, which have been observed in breast cancer cells, are minimally or not expressed in normal human tissue and have been considered as antigen tumor-specific. For this reason they are very attractive to immunotherapy. A phase I/II clinical trial was carried out in metastatic breast cancer patients with the NGlycolylGM3/VSSP vaccine administered by subcutaneous route. Selecting the optimal biological doses of the vaccine in these patients was the principal objective based on the immunogenicity, efficacy and safety results. Six levels of doses of vaccine were studied. Treatment schedule consisted of five doses every two weeks and then monthly until reaching a fifteenth doses. Doses levels studied were 150, 300, 600, 900, 1200 and 1500 μg. Five patients in each level were included except at the 900 μg dose, in which ten patients were included. Immunogenicity was determined by levels of antibodies generated in patients after vaccination. The response criteria of evaluation in solid tumors (RECIST) was used to evaluate antitumoral effect. Safety was evaluated by Common Toxicity Criteria of Adverse Event (CTCAE). The vaccine administration was safe and immunogenic in all does levels. Most frequent adverse events related to vaccination were mild or moderate and were related to injection site reactions and “flu-like” symptoms. Vaccination induced specific anti-NeuGcGM3 IgM and IgG antibodies responses in all patients. Disease control (objective response or stable disease) was obtained in 72.7% of evaluated patients. Median overall survival was 15.9 months. Two patients of two different dose levels achieved overall survival values of about six years. The dose of 900 μg was selected as biological optimal dose in which overall survival was 28.5 months.

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