PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Clinical Trials, Phase III as Topic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2002

Therapy choices among older patients with lung carcinoma: an evaluation of two trials of the Cancer and Leukemia Group B.

BACKGROUND: Despite a greater risk of malignancy and a higher cancer mortality rate for patients age > 65 years, bias in accruing older patients to clinical trials persists. The results from two National Cancer Institute-approved cooperative group trials (Cancer and Leukemia Group B trial 8931 [CALGB 8931] and CALGB 9130) were analyzed retrospectively to determine the participation, tolerance of treatment, and outcome of patients age > 70 years. METHODS: Five hundred fifteen patients with locally advanced or metastatic nonsmall cell lung carcinoma participated in two separate, randomized, Phase III clinical trials conducted by CALGB. Retrospective evaluation of patients by four distinct age cohorts (< 50 years, 50-59 years, 60-69 years, and > 70 years) was carried out to determine differences in toxicity, response, and survival. RESULTS: No patients age > 80 were entered on either study, even though there was no age restriction in the study eligibility criteria. No significant differences were seen in response, survival, or continuation of treatment based on age cohort. Significantly increased leukocyte toxicity was seen in older cohorts without a concomitant increase in severe or worse infectious events. CONCLUSIONS: No patients age > 80 were entered on either trial despite their potential eligibility. Patients in the oldest cohort showed no negative impact of age on treatment tolerance, response to treatment, or survival. The aggregate clinical judgment of patients and physicians can identify septuagenarians who should not be denied active consideration for aggressive management of their advanced nonsmall cell lung carcinoma.

Adult↗
PubMed1996

Telephone-based nursing intervention improves the effectiveness of the informed consent process in cancer clinical trials.

PURPOSE: Here we report the results of a randomized study undertaken to test the efficacy of a supplementary, telephone-based nursing intervention in increasing patients' awareness and understanding of the clinical trials in which they are asked to participate. METHODS: During a 12-month period, 180 cancer patients who were approached to participate in a phase II or III clinical trial were randomized to undergo either of the following: (1) standard informed consent procedures based on verbal explanations from the treating physician plus written information (controls); or (2) standard informed consent procedures plus a supplementary, telephone-based contact with an oncology nurse (intervention). For purposes of evaluation, face-to-face interviews were conducted with all patients approximately 1 week after the informed consent process had been completed. RESULTS: The two groups were comparable with regard to sociodemographic and clinical variables. Both groups had a high level of awareness of the diagnosis and of the nature and objectives of the proposed treatments. The intervention group was significantly (P < .01) better informed about the following: (1) the risks and side effects of treatment; (2) the clinical trial context of the treatment; (3) the objectives of the clinical trial; (4) where relevant, the use of randomization in allocating treatment; (5) the availability of alternative treatments; (6) the voluntary nature of participation; and (7) the right to withdraw from the clinical trial. The intervention did not have any significant effect on patients' anxiety levels or on rates of clinical trial participation. Patients reported high levels of satisfaction with the intervention. CONCLUSION: The use of a supplementary, telephone-based nursing intervention is a feasible and effective means to increase cancer patients' awareness and understanding of the salient issues that surround the clinical trials in which they are asked to participate.

Adult↗
PubMed2001

What have we learnt from previous phase II trials to help in the management of childhood brain tumours?

Contrary to major advances in cure rates observed for almost all childhood cancers, progress in reducing brain tumour survival rates remains very limited. Although new drug development in oncology is founded on principles outlined in the organised methodology of phase I, II, and III trials, based on rigorous study design using standardised criteria, this approach has been applied very slowly in the field of neuro-oncology. There are multiple explanations for the paucity of well-conducted prospective clinical trials, such as the rarity and the heterogeneity of these tumours, and the reluctance of some investigators to enroll their patients in constraining trials. Data from the past two decades shows that several methodological problems preclude the drawing of any definite conclusions for the majority of drugs assessed. Among them, the necessity of a central neuropathological and neuroradiological review has been highlighted in, at least, two multicentric studies. Changes in histological diagnosis and grade have been reported in a proportion as high as 20%, and changes in response rate in 14% of the cases. This review of phase II trials for brain tumours reveals a wide array of sometimes arbitrary response definitions, that is if response is defined at all, and most series have enrolled small numbers of patients. We report on the different problems encountered in childhood brain tumours in these phase II trials, and their impact on phase III trials.

Antineoplastic Agents↗
PubMed2003

Technology evaluation: HSPPC-96, antigenics.

Antigenics is developing HSPPC-96, a vaccine based on heat shock protein for the potential treatment of various cancer indications. The compound is currently undergoing phase III clinical trials for renal cell carcinoma and melanoma.

Animals↗
PubMed2003

Irinotecan (Campto) in the treatment of pancreatic cancer.

Irinotecan (Campto) is a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer. Single-agent irinotecan has also demonstrated modest activity in a number of other advanced solid tumors, including lung, gastric and pancreatic cancer. Preclinical data suggest a potentially additive and/or synergistic interaction between irinotecan and gemcitabine (Gemzar). This combination has demonstrated improved response rates in patients with pancreatic cancer. Unfortunately, a recently reported Phase III trial of gemcitabine with or without irinotecan revealed no survival benefit for the combination. Future combinations of irinotecan continue to be explored in an effort to further improve the treatment of this relatively chemorefractory disease. Thus far, no single agent or combination has been shown to be superior to gemcitabine alone as palliative therapy for advanced/metastatic pancreatic cancer. A promising combination of irinotecan with oxaliplatin (Eloxatin) and fluorouracil will be assessed in a Phase III study.

Animals↗
PubMed2001

ISIS-3521. Isis Pharmaceuticals.

ISIS-3521 is a 20-mer antisense phosphorothioate oligonucleotide PKCa expression inhibitor, under development by Isis (formerly in collaboration with Novartis) for the potential treatment of solid tumors that are refractory to, or recurrent with, standard treatment regimens [175741]. In November 1999, Novartis announced that it would end its codevelopment of ISIS-3521 [348221], [348222]. In August 2001, Eli Lilly in-licensed ISIS-3521 [420062]. In October 2000, phase III trials of ISIS-3521, in combination with carboplatin and paclitaxel, were initiated for the treatment of non-small cell lung cancer (NSCLC) [386128]. The FDA granted ISIS-3521 Fast Track review status for NSCLC in November 2000 [388930]. In April 2001, Bear Sterns & Co predicted US approval of ISIS-3521 in 2002 [411081]. In August 2001, Eli Lilly and Isis entered into a four-year strategic alliance that includes ISIS-3521. For the license of ISIS-3521, Isis will receive $25 million in upfront fees and will be reimbursed for remaining phase III development and registration costs [420062].

Animals↗
PubMed2003

Cytokine-based therapy for metastatic renal cell cancer.

The use of recombinant gene technology to produce commercially available amounts of cytokines heralded an era of clinical applications of immunotherapy. Although the response rates to cytokine therapies are modest and sometimes occur at the expense of great cost and toxicity, they are proof of the principal that even large tumor burdens can be overcome by purely immune modulation. The interleukins and the interferons have been used in various phases of clinical trials in RCC. The maturation and final results of phase III trials are needed to guide clinical practice. In the meantime, the knowledge gained clinically and in the laboratory should lead to continued improvements and outcomes in immunotherapy for RCC.

Carcinoma, Renal Cell↗
PubMed1995

Interferon beta-1b in secondary progressive multiple sclerosis--outline of the clinical trial.

This manuscript describes the outline of a double-blind, placebo-controlled, (European), multicentre phase III study to evaluate the safety and efficacy of 8 MIU of interferon beta-Ib given subcutaneously every other day for 3 years in patients with secondary progressive multiple sclerosis. The primary efficacy variable of this trial is the time to confirmed neurological deterioration as documented by the Expanded Disability Status Scale. The essentials of the study design are presented, including the rationale for the performance of the study and the selection of both clinical and magnetic resonance imaging outcome parameters.

Adjuvants, Immunologic↗
PubMedDate not supplied

Use of photodynamic therapy for the management of pleural malignancies.

Photodynamic therapy (PDT) is a surface oriented, locally cytotoxic intervention being investigated for oncologic therapy. Surfaces such as the pleura or the peritoneum are frequently involved with primary or metastatic cancer, and the chance for cure in such situations is low due to the inability to eradicate all the disease. A series of investigations have been performed at the National Cancer Institute since 1985 studying the possible use of PDT for large cavity treatment. This report details evolution of the methodology, toxicity, and overall feasibility of the delivery of intrapleural PDT to patients after debulking of primary and malignant chest neoplasms, with an emphasis on malignant pleural mesothelioma. These investigations have culminated in an ongoing Phase III trial to define the efficacy of intrapleural PDT.

Animals↗
PubMed2000

[Radiochemotherapy in anal canal epidermoid cancer].

Epidermoid anal canal carcinomas are radio- and chemosensitive tumors. Within a few decades, conservative treatment has replaced mutilating surgery as standard therapeutic practice. Exclusive high-dose radiotherapy remains the standard treatment of early stages T1-T2 N0 smaller than 4 cm. Three phase III trials demonstrated the benefits of combined chemotherapy and irradiation on the local efficacy and colostomy-free survival. Mitomycin C and 5 FU were delivered on weeks 1 and 5 of the irradiation. Concomitant 5 FU and CDDP regimen and neoadjuvant chemotherapy were evaluated on phase II trials. Ongoing intensification phase III trials are described.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Pregabalin (Pfizer).

Pregabalin is a gamma-aminobutyric acid analog that is under development by Pfizer for the potential treatment of central nervous system disorders, including epilepsy, neuropathic pain, fibromyalgia and generalized anxiety disorder. By April 2003, Pfizer had filed for approval of pregabalin in Europe for neuropathic pain and as an adjunctive therapy for epilepsy, and in October 2003 an NDA was filed for these indications and generalized anxiety disorder. At this time, phase III trials in fibromyalgia were ongoing.

Analgesics, Non-Narcotic↗
PubMed1998

[Place of surgery in a multidisciplinary approach to stage III non-small-cell cancers].

Results of isolated surgical resection for stage III lung cancer are not satisfactory, since overall 5-year survival rates rarely exceed 15%. Deaths during follow-up are mainly due to metastatic progression. The multimodality approach adds chemotherapy to surgery, with the intent to improve the control of micrometastatic disease which potentially exists at the time of diagnosis. Preoperative or neoadjuvant chemotherapy is currently under evaluation. Phase 2 trials demonstrate a treatment-related mortality of 5%: complete response and partial response are rated 5-10% and 50% respectively. About 85% of patients are operated upon within an average of 3 months after onset of treatment. Exploratory thoracotomy without resection is performed in 15% of cases; a complete resection may be performed in 75% of cases. Overall post-operative mortality is close to 5%, but considerably higher rates of 10-17.5% have been reported following pneumonectomy. Median survival after treatment may reach 20 months. Indicators of improved survival are response to induction therapy and complete resection. However, ther is no objective evidence that induction therapy improves survival after resection. Interpretation of phase 2 trials is obscured by methodologic drawbacks such as heterogenous patient samples or inaccurate staging. The spare phase 3 trials suffer from identical drawbacks, and further from too short sample sizes. Mediastinoscopy prior to induction therapy is mandatory to confirm N2 or N3 disease, because radiologic staging is not reliable. Pathologic and therefore accurate staging is achieved when surgical resection is the initial step of treatment. Previous work has concluded that post-operative or adjuvant chemotherapy does not improve survival; however, these trials did not use optimal drug regimens, and compliance to treatment was not satisfactory. In fine, the 2 major objectives of surgery in the multimodality setting are to secure local control of the disease, and to confirm stage III disease owing to pathologic stating.

Carcinoma, Non-Small-Cell Lung↗
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↗
PubMed2003

MK-767. Kyorin/Banyu/Merck.

MK-767 (KRP-297, L-410198) is a peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma agonist under development by Banyu, Kyorin and Merck for the potential treatment of diabetes. The compound is currently undergoing phase III trials in the US and phase I trials in Japan.

Animals↗
PubMed2003

Exenatide. Amylin/Eli Lilly.

Amylin Pharmaceuticals Inc and Eli Lilly & Co are co-developing exenatide (AC-2993; synthetic exendin-4), a 39-amino acid, glucagon-like peptide-1 agonist derived from the venom of the Gila monster lizard (Heloderma suspectum) as a potential injectable treatment for type 2 diabetes. The first phase III trial (exenatide as a monotherapy) was initiated in December 2001. In January 2002 the second phase III trial, of exenatide in conjunction with sulfonylureas, was initiated and in March 2002, Amylin initiated the third phase III trial, of exenatide in combination with metformin and sulfonylureas.

Animals↗
PubMed2005

Pharmacokinetic-pharmacodynamic comparison of a novel multiligand somatostatin analog, SOM230, with octreotide in patients with acromegaly.

OBJECTIVE: Acromegaly is a serious hormonal disorder resulting from a pituitary adenoma causing excess growth hormone (GH) production. Somatostatin analogs such as octreotide have been the medical treatment of choice. SOM230, a novel somatostatin analog, was compared with octreotide with respect to pharmacokinetic (PK) profiles and inhibition of GH secretion in acromegalic patients. METHODS: In a double-blind, 3-period, crossover, proof-of-concept study, 12 patients with active acromegaly were randomized to single subcutaneous doses of SOM230 (100 and 250 microg) and octreotide (100 microg). Concentrations of SOM230, octreotide, and GH were determined at designated times after dosing and at baseline. The PK properties of SOM230 and octreotide and the relationship of PK with GH were investigated by a nonlinear mixed-effects modeling analysis. RESULTS: The apparent clearance for SOM230 is approximately half of that for octreotide (8.0 L/h versus 15.8 L/h). The elimination half-life for SOM230 is about 5 times longer than that for octreotide (11.8 hours versus 2.3 hours). The relationship between GH levels and plasma concentrations of SOM230 and octreotide is well described by a direct inhibitory model. The test drug concentration level at which half of the maximum drug effect is observed (EC50) is 46 and 553 pg/mL for octreotide and SOM230, respectively, with large interpatient variability (coefficients of variation, 164% and 65%, respectively), mainly attributable to the heterogeneous responses among patients. CONCLUSIONS: SOM230 demonstrates a lower clearance and longer half-life than octreotide, which compensates for the lower potency in GH inhibition. As a result of the lower interpatient variability for EC50 , SOM230 is expected to have a more uniform clinical GH inhibition than octreotide for acromegalic patients at a clinically effective dosing regimen.

Acromegaly↗
PubMed2004

Myocardial protection at a crossroads: the need for translation into clinical therapy.

Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery).

Animals↗