Clinical outcome for patients with metastatic colorectal cancer (mCRC) enrolled in phase I clinical trials: Single institution experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13550-e13550
Author(s):  
Umang Shah ◽  
Gopichand Pendurti ◽  
Umang Swami ◽  
Yijuan Hou ◽  
Mohammad Haroon Ghalib ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Phase I ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Phase Iii ◽  
Cancer Drug ◽  
Phase I Trials ◽  
Survival Times ◽  
Phase I Clinical Trials ◽  
Phase I Studies

e13550 Background: Phase I studies are a fundamental step in anti-cancer drug development. Prior meta-analysis looking at phase I studies showed an overall response rate (ORR) of 10.6 % and grade 4 toxicity rate of 14.3 %, and specifically, patients (pts) with mCRC enrolled in phase I trials had an ORR of 1.3 %. Herein, we report the results of a 12-year experience from our institution. Methods: Records from pts with metastatic colorectal adenocarcinoma enrolled in phase I studies at our institution from January 1999 to December 2010 were reviewed. Recorded data included treatment related responses, survival times and adverse events (AE). Kaplan-Meier analysis, t-test and X2 tests were used to analyze data. A Cox proportional-hazard model using clinical parameters at enrolment was used to predict survival. Results: Our cohort included 141 pts with mCRC (83% colon and 17% rectum) enrolled in 25 unique phase I trials. Median patient age at enrolment was 59 years, 66% were female and 81% had an ECOG PS of 0-1. Pts received a median of 3 lines of chemotherapy prior to enrolment. The median overall survival (OS) was 8.9 months. The ORR was 4.2%. The clinical benefit rate (ORR or stable disease for ≥ 4 months) was 22%. Univariate analysis showed that being female (P=0.02), Hb <12 g/dL (P=0.01), Alb < 4 g/dL (P=<0.001), Alkaline phosphatase > 150 U/L (P=<0.001) and LDH ≥ 300 U/L (P=<0.001) were independently associated with shorter survival. Multivariate analysis showed that females (HR of 2.81 95% CI 1.71-4.59, p= <0.001), Hb ≥ 12 g/dL (1.67, 95%CI 1.03-1.71, p=0.04), Alb < 4 g/dL (HR 2.51, 95% CI 1.59-3.98, p= <0.001) and LDH ≥300 U/L (HR 2.59, 95% CI 1.65-4.03, p= <0.001) were associated with shorter survival. Grade 3/4 non-hematological and hematological AE were seen in 25% and 45% of patients, respectively. Conclusions: This cohort of pts that received a median of 3 prior lines of therapy had a median OS and ORR of 8.9 months and 4.2%, respectively. These findings are similar to the ones reported in the recent phase III trial using regorafenib. Interestingly, multivariate analysis showed that a Hb of ≥ 12g/dL was associated with worse survival, in agreement with prior reports in which red cell growth factors were used.

Analysis of renal function in patients entered onto CTEP-sponsored phase I studies since 1979

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2519-2519 ◽  
Author(s):  
W. M. McHayleh ◽  
R. Sehgal ◽  
D. M. Potter ◽  
R. B. Royds ◽  
T. G. Nekrassova ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Renal Function ◽  
Phase I ◽  
Creatinine Clearance ◽  
Renal Dysfunction ◽  
Antineoplastic Agents ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Phase I Studies ◽  
Administration Methods

2519 Background: The NCI and FDA utilize different criteria for classifying renal dysfunction. We analyzed renal function in all patients entered onto CTEP-sponsored phase I clinical trials since 1979 to evaluate the percentage of patients with acceptable renal function according to criteria utilized by the National Cancer Institute, as compared with those advocated by the Food and Drug Administration. Methods: Data from 12575 patients entered onto CTEP-sponsored phase I studies since 1979 were evaluated. Renal function was characterized by calculating creatinine clearance (CrCl) by three different formulae (Cockroft-Gault, Jelliffe, and Levey), as well as GFR according to MDRD. Results: Of the 12,575 patients, data were available to calculate renal function with all the 4 formulae in 5,177. Distributions of CrCl and GFR were defined, and patients were classified as having normal renal function or severe, moderate, or mild renal dysfunction according to FDA or NCI criteria. The resulting distributions are indicated in the table below. Conclusions: Approximately 40% of patients entered into CTEP-sponsored phase I trials have mild renal dysfunction according to FDA criteria and approximately 95% have CrCls > 50 ml/min. These data imply that moderate and severe are the only renal dysfunction categories that need to be evaluated in renal dysfunction studies of novel antineoplastic agents and that FDA guidelines should be applicable. Whether patients in the NCI database with CrCls of 50–80 ml/min experience more toxicities than those with creatinine clearances > 80 ml/min is undergoing evaluation. [Table: see text] [Table: see text]

Characteristics and outcomes of patients with advanced hepatocellular carcinoma treated on phase I trials.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
Ishwaria Mohan Subbiah ◽  
Filip Janku ◽  
Apostolia Maria Tsimberidou ◽  
Aung Naing ◽  
Ahmed Omar Kaseb ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Phase I ◽  
Serum Sodium ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Single Agent ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase I Trials ◽  
Phase I Clinical Trials

281 Background: Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapies. With that purpose, we analyzed the outcomes and prognostic factors of such pts treated on phase I trials w an emphasis on locoregional and targeted agents. Methods: We reviewed the records of 100 consecutive pts referred to the Phase I Clinical Trials Program from March 2004 and assessed characteristics, types of clinical trials, progression-free survival (PFS), overall survival (OS) and oncogenic mutations. Results: Of 100 referred pts, 39 were not treated mainly due to poor performance status (n=22). Of 61 treated pts (49 male, 12 female, median age 60yrs), median # of prior therapies was 3 (range, 0-8). There were no treatment-related mortalities. One pt on a sorafenib regimen had g3 hand foot syndrome unresponsive to dose reduction. A 2nd pt developed a L-sided visual blurriness after 5 days on a sunitinib regimen; CT showed a small R parieto-occipital hemorrhage, possibly related to therapy. Of 61 treated pts, 7 (11%) had stable disease (SD) > 6 months, 4 (7%) partial response (PR), on protocols combining bevacizumab+sorafenib, pazopanib+everolimus, or single-agent novel oral multikinase inhibitor of VEGFR2-TIE2, or hepatic arterial infusion (HAI) of paclitaxel or oxaliplatin w IV bevacizumab. Median PFS on Phase I trials was 2.2 months vs. 4.4 months and 4.1 months for their 1st- and 2nd-line FDA-approved therapy (p 0.019). In univariate analysis, the presence of ascites, portal hypertension, cirrhosis, serum sodium, albumin, and poor Royal Marsden Hospital (RMH) prognostic score were associated with shorter PFS and OS (p < 0.05). On multivariate analysis, independent factors of shorter OS were Caucasian race (p = 0.031), cirrhosis (p = 0.016), serum sodium (p = 0.0013), and poor RMH prognostic score (p = 0.0015). Molecular analysis in progress will be updated. Conclusions: Phase I therapy offer a reasonable therapeutic option for patients with advanced HCC. The RMH prognostic score was validated in this population. The SD > 6 months/PR rate of 18% was observed with regimen of multikinase inhibitors with mTOR inhibitors and HAI therapy.

The role of phase I clinical trials in advanced malignant melanoma: Retrospective analysis of CTEP-sponsored trials 1995-2011.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2606-2606
Author(s):  
Jason John Luke ◽  
Larry Rubinstein ◽  
Gary L Smith ◽  
S. Percy Ivy ◽  
Pamela Jo Harris
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase 1 ◽  
Therapeutic Benefit ◽  
Phase Iii ◽  
Phase I Trials ◽  
Toxicity Data ◽  
Phase I Clinical Trials ◽  
Exact Test ◽  
Phase Iii Clinical Trials

2606 Background: Standard chemotherapy for melanoma is DTIC (RR ~10%). Many physicians do not refer to phase I due to perceived limited clinical benefit (CB=CR+PR+SD) and increased toxicity. To understand the actual experience of melanoma patients (pts) in phase I trials, we analyzed the outcomes of melanoma pts treated on CTEP phase 1 trials (1995-2011) and compared them to DTIC. Methods: We queried the CTMS of CTEP for phase I trials in which advanced melanoma pts were treated. Trials were separated into targeted (T), chemo (C) and immunotherapy (I). Pt characteristics, response and toxicity data were collected. Chemotherapy included chemo with targeted or immunotherapy. Toxicity was drug related if attributed possibly, probably or definitely to drug. Fisher’s Exact Test (2-sided p) was used to compare groups. DTIC data was pooled from 6 modern phase III clinical trials (1999-2011). Results: 937 pts (M595:F342) participated in 148 trials (T: 68, C: 53, I: 27). Characteristics included (median) Age: 51.5 yrs; ECOG status: 0; Prior therapies: 2 (majority receiving prior DTIC); LDH: 206 and albumin: 4.1. Response and toxicity data are shown in the Table. Targeted therapy was associated with lower RR (p=.01), immuno with lower CB rate (p<.001) and chemo with higher incidence of G4 toxicity (p<.001) relative to the other groups. Comparing phase 1 to DTIC, RR and CB were not clinically different (phase I: 6.3% and 26.8% vs. DTIC: 8.8% and 27.9%) but G3-4 toxicity was significantly higher (54% vs. 28%) in phase I (p<.0001). Conclusions: Melanoma pts in prior CTEP phase I trials, a majority DTIC pre-treated, had similar therapeutic benefit but more toxicity compared to DTIC naïve pts in modern clinical trials. [Table: see text]

Risks and benefits of phase I trials: Eighteen-year experience from a single institution.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18146-e18146
Author(s):  
Audrey E. Kam ◽  
Imran Chaudhary ◽  
Mohammad Haroon Ghalib ◽  
Umang H. Shah ◽  
Umang Swami ◽  
...  
Keyword(s):  
Phase I ◽  
Meta Analysis ◽  
Phase I Trials ◽  
Single Institution ◽  
Phase I Studies ◽  
Kaplan Meier ◽  
Recorded Data ◽  
Third Line ◽  
Grade 3 ◽  
Recruitment Barriers

e18146 Background: Phase I trials are a critical component of drug development; yet are considered non-therapeutic. This leads to recruitment barriers due to provider and patient discomfort. The largest meta-analysis of phase I studies has previously shown a response rate (RR) of 10.6%. Herein we report the results from our institution. Methods: Records of patients enrolled on phase I trials at our institution from January 1999 to December 2016 were reviewed. Recorded data included adverse events (AE); treatment related responses and deaths. Kaplan-Meier analysis and t-test were performed on the reviewed data. Results: During this period 774 patients were accrued on 64 phase I trials [43.8% cytotoxic, 45.3% biological, 6.2% both and 4.7% viral agents]. Primary cancer diagnoses included colorectal (25.2%), ovarian (17.6%), lung (7.8%), uterine (6.6%) and breast (6.1%). In total, 609 patients were evaluable for response, 41.1% had stable disease (SD) and overall RR was 7.7% (complete RR = 1.0%). Patients with overall clinical benefit (SD+response) had lower mean baseline WBC (4.83 vs 5.94 k/uL, p = 0.0008), ANC (2.92 vs 4.12 k/uL, p = 0.00007), platelets (209 vs 246 k/uL, p = 0.00007), LDH (280 vs 346 U/L, p = 0.0055) and higher serum albumin (3.97 vs 3.86 g/dL, p = 0.011) as compared to patients with progressive disease. Grade 3/4 non-hematological and hematological AE were seen in 28.5% and 19.9% patients, respectively. Treatment-related mortality was 0.8%. Patients with baseline LDH below the median (247 U/L) for the cohort had a higher median survival (312 days vs 201 days, p < 0.001, HR 0.61 95% CI 0.51-0.73). The median and mean duration on study were 56 and 87 days, respectively. Conclusions: This is one of the largest single-institution series of phase I oncology trials. Our RR of 7.7% [95% CI 5.9-10.1%] falls within the 95% CI of the RR of a majority of third line (and greater) chemotherapy regimens for solid tumors. Thus, the concept of 'non-therapeutic' nature of phase I studies needs reconsideration.

scholarly journals Random-effects meta-analysis for systematic reviews of phase I clinical trials: Rare events and missing data

2016 ◽  
Vol 8 (2) ◽  
pp. 124-135 ◽  
Author(s):  
Mi-Ok Kim ◽  
Xia Wang ◽  
Chunyan Liu ◽  
Kathleen Dorris ◽  
Maryam Fouladi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Missing Data ◽  
Phase I ◽  
Random Effects ◽  
Systematic Reviews ◽  
Rare Events ◽  
Meta Analysis ◽  
Phase I Clinical Trials

scholarly journals Self-Replicating RNA Viruses for RNA Therapeutics

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3310 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Antibody Responses ◽  
Phase Iii ◽  
Phase I Clinical Trials

Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.

scholarly journals Healthy Volunteers’ Perceptions of the Benefits of Their Participation in Phase I Clinical Trials

2018 ◽  
Vol 13 (5) ◽  
pp. 494-510 ◽  
Author(s):  
Jill A. Fisher ◽  
Lisa McManus ◽  
Megan M. Wood ◽  
Marci D. Cottingham ◽  
Julianne M. Kalbaugh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
Employment Status ◽  
Qualitative Interviews ◽  
Trial Participation ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Financial Compensation ◽  
Trial History

Other than the financial motivations for enrolling in Phase I trials, research on how healthy volunteers perceive the benefits of their trial participation is scant. Using qualitative interviews conducted with 178 U.S. healthy volunteers enrolled in Phase I trials, we investigated how participants described the benefits of their study involvement, including, but not limited to, the financial compensation, and we analyzed how these perceptions varied based on participants’ sociodemographic characteristics and clinical trial history. We found that participants detailed economic, societal, and noneconomic personal benefits. We also found differences in participants’ perceived benefits based on gender, age, ethnicity, educational attainment, employment status, and number of clinical trials completed. Our study indicates that many healthy volunteers believe they gain more than just the financial compensation when they accept the risks of Phase I participation.

scholarly journals Race and ethnicity representation in clinical trials: findings from a literature review of Phase I oncology trials

2021 ◽  
Author(s):  
D Ross Camidge ◽  
Haeseong Park ◽  
Karen E Smoyer ◽  
Ira Jacobs ◽  
Lauren J Lee ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Predominantly White ◽  
Race And Ethnicity ◽  
Phase I Trials ◽  
Minimal Representation ◽  
Phase I Clinical Trials ◽  
Demographic Representation ◽  
The Usa ◽  
Race Ethnicity

Aim: To provide an assessment of published literature on the demographic representation in Phase I trials of biopharmaceutical oncology agents. Materials & methods: We conducted a rapid evidence assessment to identify demographic representation reported in Phase I clinical trials for biopharmaceutical oncology agents published in 2019. Results: Globally, the population was predominantly White/Caucasian (62.2%). In the USA, the distribution was heavily skewed toward White/Caucasian (84.2%), with minimal representation of Blacks/African–Americans (7.3%), Asians (3.4%), Hispanics/Latinos (2.8%) or other race/ethnicity groups. Conclusion: Our data highlight that Phase I oncology trials do not reflect the population at large, which may perpetuate health disparities. Further research is needed to understand and address barriers to participation, particularly among under-represented groups

Low-Grade Stage III-IV Follicular Lymphoma: Multivariate Analysis of Prognostic Factors in 484 Patients—A Study of the Groupe d'Etude des Lymphomes de l'Adulte

1999 ◽  
Vol 17 (8) ◽  
pp. 2499-2499 ◽  
Author(s):  
Didier Decaudin ◽  
Eric Lepage ◽  
Nicole Brousse ◽  
Pauline Brice ◽  
Jean-Luc Harousseau ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Risk Ratio ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Phase Iii ◽  
Stage Iii ◽  
Low Grade ◽  
Number Of Patients ◽  
Follicular Lymphomas

PURPOSE: To identify the prognostic factors that influence overall survival (OS) in patients with stage III-IV follicular lymphomas and evaluate the clinical usefulness and the prognostic value of the International Prognostic Index (IPI). PATIENTS AND METHODS: Four hundred eighty-four patients with Ann Arbor stage III-IV follicular lymphomas treated in two phase III trials from 1986 to 1995 were screened for this study. All histologic slides were reviewed by two hematopathologists. The influence of the initial parameters on survival was defined by univariate (log-rank test) and multivariate (Cox model) analyses. RESULTS: The poor prognostic factors for OS (age > 60 years, “B” symptom(s), ≥ two extranodal sites, stage IV disease, tumor bulk > 7 cm, at least three nodal sites > 3 cm, liver involvement, serous effusion-compression or orbital/epidural involvement, and erythrocyte sedimentation rate > 30 mm/h) that were significant in univariate analysis were subjected to multivariate analysis. Three factors remained significant: B symptom(s) (risk ratio = 1.80), age greater than 60 years (risk ratio = 1.60), and at least three nodal sites greater than 3 cm (risk ratio = 1.71). When the IPI was applied to these patients, the score was 1, 2, 3, and 4-5 in 49%, 39%, 11%, and 2%, respectively, and it was significant for progression-free survival (P = .002) and OS (P = .0001). CONCLUSION: Three prognostic factors for poor OS were identified: B symptoms, age greater than 60 years, and at least three nodal sites greater than 3 cm. The IPI was prognostic for OS, but in this population, a very low number of patients belonged to the high-risk groups.

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