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Results for “Clinical Trials, Phase II as Topic”

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At least 19 recordsLinked to original sources
PubMed2004

Therapeutic vaccine trails in Thailand.

An effective therapeutic HIV vaccine will not only benefit the HIV-infected person but will also provide invaluable information on effective immune response in designing or selecting a preventive vaccine. A phase II double-blind controlled clinical trial using HIV-1 immunogen (Remune) was undertaken in Thailand in 1995 in conjunction with phase III approval in the USA. In most instances, immune response to the virus was induced. The results from this study led to the extension of further trials over the following 4 years. At present, the Thai Food and Drug Administration (FDA) is in the process of reviewing the files on all information to assess the effectiveness of this therapeutic vaccine as well as reviewing the proposal to conduct a phase III trial to further confirm previous efficacy results from the phase II trials.

AIDS Vaccines↗
PubMed2001

Recommendations for clinical trial evaluation of acute stroke therapies.

The development of therapies for acute ischemic stroke has achieved a few notable successes and, unfortunately, many unsuccessful efforts. Many valuable lessons for the future assessment of new acute stroke therapies can be gleaned from the positive and negative prior trials. Phase I and II trials must be carefully designed and implemented to derive relevant, valuable information needed to proceed to phase III trials with promising interventions. The phase III trial should evaluate drug efficacy in an appropriately targeted stroke population evaluated by a meaningful and reliable outcome measure. Combinations of various types of stroke therapies will likely be increasingly assessed in future trials that are designed and implemented by cooperative efforts between the pharmaceutical industry, government agencies, academic advisors and clinical investigators. The chances for future success in demonstrating efficacy with acute stroke therapies will be enhanced by carefully conceived, scientifically based clinical trials. The recommendations contained in this document may help to focus attention on how to achieve the goal of developing an expanding number of a effective and safe acute stroke therapies.

Acute Disease↗
PubMed1994

[How to assess the size of a clinical trial?].

The interpretation of the results of a clinical trial, an experimental method now recognised as the agreed technique for studying new therapeutic modes of treatment in man, is based on a statistical study of data collected on a sample of patients enrolled in the study and treated till its fulfillment. This interpretation is often made using statistical inference techniques based on the construction of a decision rule associated with a statistical hypothesis test; this hypothesis test serves to formalize a research question in a precise manner, and allows the null hypothesis H0 to be tested against an alternative hypothesis H1. The decision rule will be constructed using a probability distribution, which assumes control against type I error, and consists of falsely rejecting the null hypothesis. However, the control of the risk of type II error, made error where one mistakenly takes a decision not to reject the null hypothesis, can only be achieved using a sufficiently large sample. The correct evaluation of the sample size is thus paramount if one does not wish to be doomed to the failure of a study, by including an insufficient number of patients to achieve the aimed objective. The aim of this report is to review how this evaluation can be due, in a practical manner without proof, in the context of simple situations which are used when Phase II or III clinical trials are put into action.

Clinical Trials as Topic↗
PubMed1995

Clinical trial design in metastatic breast cancer: a commentary.

Trial designs traditionally used in the development of new anti-cancer agents are usually categorized as phase I, phase II, phase III and phase IV. Such trials are often performed in patients with metastatic cancer. Phase I trials are conducted in small numbers of patients to determine a drug's maximally tolerated dose (MTD) and toxicity profile. In phase II studies, the anti-tumor activity of the new agent is tested in different tumor types. If a drug is found to be promising in phase II studies, it is then compared to standard therapy through a randomized trial design in phase III studies. In phase IV studies, the efficacy and safety profile of the drug are evaluated in a standard clinical setting. In the field of oncology, studies have been conducted in which agents already approved by the regulatory agency are combined with other anti-cancer drugs and evaluated for anti-tumor efficacy. These have also been termed phase II studies.

Antineoplastic Agents↗
PubMed2001

Paclitaxel added to the cisplatin/etoposide regimen in extensive-stage small cell lung cancer -- the use of complete response rate as the primary endpoint in phase II trials.

Obtaining a complete response (CR) is the most powerful predictor of survival in extensive-stage small cell lung cancer (SCLC). Improvements in long-term survival in extensive-stage SCLC can be made if the proportion of complete responders to induction therapy can be increased. We performed a phase II trial of the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP regimen) in extensive-stage SCLC. The primary endpoint for this trial is the proportion of patients (pts) obtaining a CR rather than overall response. The null hypothesis for this trial consists of the absence of a CR rate >20%. Paclitaxel was given at doses of 135 (3 pts) or 170 mg/m(2) i.v. over 3 h on day 1. Cisplatin 60 mg/m(2) was given on day 1. On days 1-3 etoposide 80 mg/m(2) per day i.v. was given. G-CSF was used from days 5 to 14 of each cycle. Cycles were repeated q21 days. A two-stage design was used for patient accrual, based on the occurrence of complete responses. Initially, 16 patients were to be accrued. If more than three complete responses were to occur, a further 20 patients would be accrued to the study (Simon's optimal two stage design). Sixteen patients were enrolled. Two patients had a CR (13%) and nine patients had a partial response (56%) for an overall response rate of 69%. The trial was suspended due to the low CR rate. Review of the literature for paclitaxel based front-line treatment combined with EP therapy, in extensive stage SCLC, consistently shows a CR rate <20% but high overall response rate is maintained (thus most responses are partial). As virtually all long-term survivors in extensive-disease SCLC have had a CR to induction therapy and CR remains the strongest predictor of survival for this disease, this may suggest that paclitaxel added to standard EP may improve progression-free survival (and possibly median survival) but is unlikely to significantly improve long-term survival. Initial randomized phase III data confirm the absence of impact on survival for this triple-drug regimen compared to EP therapy alone. Furthermore, other regimens comparing favorably to the EP regimen have all shown consistent CR rates >20% in the phase II setting. In conclusion, consideration should be given to the use of CR rate as a phase II endpoint to determine if a particular regimen should be compared to the standard in a phase III setting for extensive-stage SCLC. A two-stage phase II design based on a minimum required completed responses for further patient accrual is recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

ChimeriVax-JE. Acambis.

Acambis (formerly Peptide Therapeutics Group) is developing a vaccine for the potential prophylaxis of Japanese encephalitis (JE) virus infections. In August 2001, Acambis commenced a phase II trial of its ChimeriVax-JE vaccine; these studies were complete by February 2002 and the company was making plans to begin an additional phase II study in children living in areas where JE is prevalent. By May 2003, Acambis had initiated a phase II trial in Australia.

Animals↗
PubMed2006

Unconventional anticancer agents: a systematic review of clinical trials.

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.

Antineoplastic Agents↗
PubMed2005

Tetomilast.

Otsuka is developing a once-daily oral formulation of the phosphodiesterase-4 inhibitor tetomilast for the potential treatment of ulcerative colitis (phase III) and chronic obstructive pulmonary disease (phase II).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Clinical trials: are they a good buy?

PURPOSE: Concern that clinical trials may be too costly has been used to justify traditionally restrictive insurer policies regarding clinical trials. Additionally, fear of insurer reimbursement denial can be a significant barrier to clinical trial participation. In this study, we reviewed the empirical data on costs of clinical trials versus standard care and summarized the current status of policy initiatives related to clinical trial insurance reimbursement. METHODS: Electronic and print data sources were searched for studies on the costs of oncology clinical trials. Information on policy initiatives for clinical trial reimbursement was obtained from the American Society of Clinical Oncology, the American Society of Hematology, and the Coalition of National Cancer Cooperative Groups and from searches of World Wide Web sites. RESULTS: Five pilot studies provided information for 377 patients on phase II/III clinical trials matched with controls on standard care. Cost estimates ranged from 10% lower to 23% higher costs/charges for clinical trials in comparison to standard medical care. Medicare, 14 states, and several private insurers now cover the costs of patient care in "qualifying" clinical trials. CONCLUSION: Findings from small pilot studies suggest that phase II and III clinical trials result in at most modest increases in cost over standard treatment costs. Also, an increasing number of policy makers have decided to support clinical trial reimbursement initiatives. It is hoped that economic data from large observational studies will facilitate widespread and permanent decisions that support reimbursement for phase I, II, and III clinical trial participation.

Clinical Trials as Topic↗
PubMed2003

Sumanirole Pharmacia.

Sumanirole is a dopamine D2 agonist under development by Pharmacia Corp (formerly Pharmacia & Upjohn) for the treatment of Parkinson's disease. The compound is currently undergoing phase II trials in Japan and phase III clinical trials in the US.

Antiparkinson Agents↗
PubMed2003

Balofloxacin Choongwae.

Balofloxacin, an orally active fluoroquinolone antibiotic, has been developed by Choongwae Pharma in Korea, for the treatment of urinary tract infection (UTI). Chugai and Ciba were developing balofloxacin for respiratory tract infections (RTI) but discontinued development in 1995 due to changes in Chugai's R&D focus and a lack of efficacy of the drug. Following phase II trials, Choongwae bought the rights to develop balofloxacin in Korea from Chugai. Phase III trials for UTI were completed in early 2001. Balofloxacin was approved by the Korean FDA in December 2001 for UTI. In March 2002, phase II trials were underway for RTI.

Anti-Infective Agents↗
PubMed2006

Drug evaluation: AMG-531 for the treatment of thrombocytopenias.

Amgen Inc is developing AMG-531, a peptibody that binds to the thrombopoietin receptor Mpl, for the potential treatment of immune thrombocytopenic purpura (ITP), chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia in myelodysplastic syndrome (MDS). Results of the US phase III trial in ITP are expected to be available in the second half of 2006, while a phase II trial in CIT is still underway. A Japanese phase II ITP study has been initiated, as has a phase II trial of MDS patients in the US and France.

Animals↗
PubMed1994

Acute lymphoblastic leukaemia in adults: the case for a strategic shift in study approach.

After 20 years of frantic chemotherapeutic activity, all concerned with adult ALL are now resigned to the fact that only some 20% of the overall adult cases are biologically similar to childhood ALL, and the majority of these are in the adolescent age groups. It is evident that as much effort as possible must be made to dissect out such chemocurable patients from the bulk of patients with adult ALL so that they might obtain cure with conventional chemotherapy, thus avoiding early transplantation or unnecessary intensification. In such a rare disease, unless we organize nationally, and look at population-based studies linked to phase III or phase II studies where appropriate, we are destined not to develop appropriate strategies for treatment of this disease for a long time to come.

Adult↗
PubMed1996

Factors influencing response rates for advanced colorectal cancer chemotherapy.

BACKGROUND: The activity of various chemotherapy regimens used in the treatment of advanced colorectal cancer is assessed by different groups of investigators and in various trials by what appear to be common criteria. However, there may be substantial inter-trial variation in the interpretation and application of these criteria which contributes to differences in response rates reported for the same regimen. MATERIALS AND METHODS: This paper reviews the most prominent studies in this field and examines the factors which may influence the assessment of activity in clinical trials such as patient selection, the definition and application of response criteria, the methods of assessment of time to progression and duration of response, factors related to the therapeutic regimen and statistical methods. Each factor is critically discussed. RESULTS: The analysis confirms that there is a large variability among the different studies and that an inter-trial comparison is often impossible, with subsequent difficulties for clinicians in determining the true impact of therapies. DISCUSSION: After briefly commenting on the various issues, this review makes recommendations about how to achieve consistency among trials, for instance by using standard criteria, by extending the use of randomization even in phase II trials and by evaluating high quality, well conducted clinical trials in a meta-analysis, thereby making possible comparison across trials. The conclusions, although specific to colorectal cancer, are also applicable to other advanced malignancies.

Antineoplastic Agents↗
PubMed2005

New paradigm in dose-finding trials: patient-specific dosing and beyond phase I.

We propose a new paradigm for the clinical evaluation of new cancer therapies. It entails adjusting the search for the optimal dose on the basis of measurable patient characteristics that may be predictive of adverse responses to treatment, and extending this search beyond phase I and into phases II and III. We provide examples of (a) how the fine-tuning of dose may involve utilization of patient-specific attributes to obtain a personalized treatment regimen, and (b) how novel methods for phase I design can be used to update the working dose for the conduct of phase II and III cancer clinical trials. These examples should be interpreted as an enticement for the development of new methods to implement the proposed new paradigm.

Antineoplastic Agents↗
PubMed2006

[Combination therapy with S-1 plus docetaxel (DOC) for previously treated patients with non-small cell lung cancer].

The present paper presents a review of the second-line treatment of non-small cell lung cancer (NSCLC) and reports a phase I study of the combination chemotherapy of docetaxel (DOC) and S-1 as second-line chemotherapy. Current options for the second-line treatment of NSCLC include cytotoxic drugs, such as DOC, pemetrexed, and targeted therapies. However, single-agent chemotherapy has shown limited activities. A new treatment approach is needed for this patient population. We hypothesized that combination chemotherapy of DOC and S-1 would be effective through the additive and synergistic activities. We performed a phase I clinical trial of this combination chemotherapy. S-1 was administered orally at a dose of 80 mg/m2 for 14 days, followed by a drug-free interval of a week (one cycle). The starting dose level (level 1) of DOC was set to 40 mg/m2, until a dose of 60 mg/m2 was reached at level 3. Three patients were treated with level 2, in which the dose of DOC was increased up to 50 mg/m2. Two of 3 patients had grade 4 neutropenia, which was determined as dose-limiting toxicity. The dose level of DOC 40 mg/m2 on day 1 in combination with S-1 80 mg/m2 for 14 days of a three week cycle was recommended for a phase II study. Partial response was achieved in 4 of the 9 patients. This combined chemotherapy consisting of S-1 and DOC may prove effective for treating recurrent cases of NSCLC. A phase II study is ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Representation of older patients in cancer treatment trials.

In 1990, the five leading causes of cancer death in men aged 65 and older were carcinomas of the lung, prostate, colon and rectum, and pancreas, and leukemia. For women in this age group, the five leading causes of cancer death were carcinomas of the lung, breast, colon and rectum, pancreas, and ovary. To determine the representation of the elderly in clinical trials, the 1992 accrual of the National Cancer Institute (NCI)-sponsored Clinical Cooperative Group treatment trials (which included more than 8000 elderly patients) for the aforementioned sites was compared with the 1990 incidence data from the NCI's Surveillance, Epidemiology, and End Results program. Of the male patients enrolled in the trials, an average of 39% were older than 65 (47.3% lung, 79.5% prostate, 47.5% colorectal, 45.6% pancreas, and 9.6% leukemia); whereas 25.9% of all women enrolled in trials were 65 or older (43.6% lung, 17.3% breast, 46.2% colorectal, 59.6% pancreas, and 35.4% ovary). With respect to incidence, older patients generally are underrepresented in cancer treatment trials. With the exception of the data on prostate cancer, each of the comparisons using the Z statistic gave probability values of less than 0.01. The most significant discrepancies between incidence and participation in cancer treatment protocols were noted for leukemia in males and breast cancer in females. Possible explanations for these findings include (1) a research focus on aggressive therapy, which may be unacceptably toxic to the elderly; (2) presence of comorbidity in the elderly; (3) fewer trials available specifically aimed at older patients; (4) limited expectations for long term benefits on the part of physicians, relatives, and the patients themselves; and (5) a lack of financial, logistic, and social support for the participation of elderly patients in clinical trials. Recognizing this situation, NCI recently sponsored a number of trials that specifically target the elderly. This paper describes the status of all major Phase II and III clinical trials that recently were closed, still are active, or now are in review that address the clinical care of this important segment of the U.S. population.

Aged↗