Personalized medicine in a phase I clinical trials program: The M. D. Anderson Cancer Center Initiative.

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. CRA2500-CRA2500 ◽  
Author(s):  
A. M. Tsimberidou ◽  
N. G. Iskander ◽  
D. S. Hong ◽  
J. J. Wheler ◽  
S. Fu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Personalized Medicine ◽  
Phase I ◽  
Molecular Analysis ◽  
Pik3ca Mutation ◽  
Molecular Profile ◽  
Cancer Center ◽  
Molecular Testing ◽  
Phase I Clinical Trials

CRA2500 Background: We initiated a personalized medicine program hypothesizing that tumor molecular analysis and use of targeted therapy to counteract the effects of specific aberrations would improve the outcomes of affected patients. Methods: Molecular analysis was performed in the M. D. Anderson CLIA-certified pathology laboratory. Patients whose tumors had an aberration were treated in the Phase I Program with a matched targeted agent, when available. Results: Tumor molecular analysis was feasible in 852 (89%) of 955 consecutive patients with advanced cancer. Of 852 patients (median, age 56 yrs; prior therapies 4), 354 (41.5%) had ≥ 1 aberration: 10% of patients had a PIK3CA mutation; 19% KRAS; 8% NRAS; 19% BRAF; 3% EGFR; and 2% had a CKIT mutation; 21% had PTEN loss. Results are shown in the table. Median time to treatment failure (TTF) in 161 patients with 1 aberration treated with matched targeted therapy was 5.3 months (95%CI: 4.1, 6.6) vs 3.2 months (95%CI: 2.9 – 4.0) for their prior systemic antitumor therapy (prior to referral to phase I) (p= .0003). For patients with 1 aberration, the CR+PR rate was 29% with matched targeted therapy vs. 8% without matching (p = .0001). The CR+PR rate was 6% in 438 patients without molecular testing treated on the same studies. Conclusions: Preliminary results suggest that in early clinical trials matching patients with targeted drugs based on their molecular profile results in (a) longer TTF compared to their prior therapy and (b) higher rates of response, survival and TTF compared to those seen in patients treated without molecular matching. Support: 3UL1 RR024148 04 S1 and IPCT. [Table: see text]

Personalized medicine in a phase I clinical trials program: The M. D. Anderson Cancer Center Initiative.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. CRA2500-CRA2500 ◽  
Author(s):  
A. M. Tsimberidou ◽  
N. G. Iskander ◽  
D. S. Hong ◽  
J. J. Wheler ◽  
S. Fu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Phase I ◽  
Cancer Center ◽  
Phase I Clinical Trials

scholarly journals Personalized Medicine in a Phase I Clinical Trials Program: The MD Anderson Cancer Center Initiative

2012 ◽  
Vol 18 (22) ◽  
pp. 6373-6383 ◽  
Author(s):  
Apostolia-Maria Tsimberidou ◽  
Nancy G. Iskander ◽  
David S. Hong ◽  
Jennifer J. Wheler ◽  
Gerald S. Falchook ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Phase I ◽  
Cancer Center ◽  
Phase I Clinical Trials ◽  
Md Anderson

Characteristics and outcomes of patients with gallbladder cancer and cholangiocarcinoma referred to a phase I clinic.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
Ishwaria Mohan Subbiah ◽  
Vivek Subbiah ◽  
Ahmed Omar Kaseb ◽  
Filip Janku ◽  
Jennifer J. Wheler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Phase I ◽  
Median Time ◽  
Median Survival ◽  
Phase I Trial ◽  
Mutational Analysis ◽  
Phase 1 ◽  
Cancer Center ◽  
Phase I Clinical Trials

364 Background: The prognosis of cholangiocarcinoma (CC) and gallbladder carcinoma (GC) remains grim. The purpose of this study was to report the presenting characteristics and outcomes of patients with CC and GC treated on phase 1 clinical trials focused on targeted agents at a major cancer center. Methods: We reviewed the records of consecutive patients with GC and CC in the Phase I Clinical Trials Program at the M. D. Anderson Cancer Center from Nov 2004. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics. Results: Fifty-two patients were identified (7 with GC, 45 with CC). The median age was 58 yrs (range, 20-75 yrs). ECOG performance status (PS) was 0, 1, 2, and 3 in 9 (17%), 30 (58%), 7 (13%), and 6 (12%) pts, respectively. Median number of prior therapies was 3 (range 0-17). The median time from diagnosis of metastatic disease to primary Phase I clinic evaluation was 14.6 months. Of 52 patients, 17 (33%) were not enrolled on a Phase I trial due to decline in PS (n=13) or decision to pursue other treatments (n=4). Of 35 patients evaluable for response, 2 (6%) had a partial response (PR), and 3 (9%) had stable disease > 4 months. Prognostic factors analyzed include Hg < 10.5 g/dL, elevated CA 19-9 (>47 ng/mL), ECOG PS > 3, LDH > 618 IU/L, albumin < 3.5 g/dL, platelets < 150 K/UL, and number of metastatic sites. Full analysis including the mutational analysis for PIK3CA, KRAS, BRAF, TP53 is in progress. Median survival since presentation to the Phase I clinic was 4.1 months (range 2.3 - 30.8 months). Median overall survival from diagnosis was 23.9 months. The median survival since enrollment in a Phase I trial was 4.6 months w the median time to disease progression on Phase I treatment was 2.2 months (range 0.6 - 25.6 months). Conclusions: Prognosis of pts with CC and GC referred for phase I studies remains poor. Further analysis including complete mutational profiles of CC and GC patients will be reported.

scholarly journals Clinical outcomes of patients with gastrointestinal malignancies participating in phase I clinical trials.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 428-428
Author(s):  
Amit Mahipal ◽  
Nancy Burke ◽  
Georgine Wapinsky ◽  
Barbara Bertels ◽  
TzuHua Juan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Liver Metastases ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Phase 1 ◽  
Cancer Center ◽  
Phase I Clinical Trials ◽  
Gastrointestinal Malignancies ◽  
Systemic Therapies

428 Background: Early phase clinical trials play a pivotal role in drug development. However, limited data is available on the clinical outcomes of patients with gastrointestinal (GI) malignancies enrolled in phase 1 clinical trials. The aim of this study is to evaluate the clinical characteristics and survival of patients with GI cancers participating in phase 1 clinical trials. Methods: All consecutive patients with advanced GI tumors who participated in phase 1 clinical trials from 1/2007 to 12/2013 at Moffitt Cancer Center were included. Data for individual patients were extracted from the OnCore database and clinical charts. Only patients who received at least one dose of the study drug were included. Cox regression model was used to estimate multivariable adjusted hazard ratios and 95% CI. Results: 243 pts with GI malignancies who participated in phase 1 clinical trials were included. Median age was 62 years (26-82 years) with 55% of the patients aged >60 years. Patients had the following disease types: pancreas (42%), colorectal (34%), gastro-esophageal (10%), hepatobiliary (13%) and others (2%). The distribution of patients for baseline variables are: male (55%), DVT/PE (12%), ECOG ≥1 (72%), prior systemic therapies ≥2 (59%), no. of metastatic sites > 2 (31%), lung metastases (40%) and liver metastases (77%). Pts received treatment with chemotherapy only (14%), targeted therapy (41%), chemotherapy + targeted therapy (42%) and others (2%). The response rate was 4% with 38% achieving stable disease; 42% of pts had progressive disease. The median OS was 5.8 months (0.2-52.4). ECOG score of 0, prior systemic therapies < 2 and absence of liver metastases were associated with better OS on multivariate analysis. Conclusions: This is the largest study to assess clinical outcomes in this patient population. Phase 1 clinical trials provide clinical benefit to patients with advanced GI malignancies and should be recommended as a treatment option in appropriate patients. [Table: see text]

scholarly journals Clinical outcomes of breast cancer patients treated in phase I clinical trials at University of Colorado Cancer Center

2020 ◽  
Vol 9 (23) ◽  
pp. 8801-8808
Author(s):  
Jennifer A. Weiss ◽  
Andrew Nicklawsky ◽  
Jodi A. Kagihara ◽  
Dexiang Gao ◽  
Christine Fisher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Phase I Clinical Trials ◽  
University Of Colorado

Patients with metastatic breast cancer enrolled in phase I clinical trials: Clinical outcomes and cohort trends.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1099-1099
Author(s):  
Jennifer Weiss ◽  
Dexiang Gao ◽  
Anthony D. Elias ◽  
Virginia F. Borges ◽  
Peter Kabos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Clinical Outcomes ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Cancer Center ◽  
Phase I Clinical Trials ◽  
Metastatic Setting

1099 Background: Phase I clinical trials have traditionally enrolled patients with advanced solid tumors and many providers perceive the likelihood of clinical benefit as low. The purpose of this study was to evaluate clinical outcomes for patients with metastatic breast cancer enrolled on Phase I clinical trials and explore differences in outcomes for patients enrolled in all-comer versus breast cancer-specific cohorts. Methods: We performed a retrospective chart review of patients with metastatic breast cancer enrolled in Phase I clinical trials at the University of Colorado Cancer Center from 2012-2018. We included trials with Phase I and/or Phase Ib in the title. Studies or cohorts enrolling patients with ≥ 3 tumor types were considered all-comer and those with enrollment restricted to breast cancer or a breast cancer subtype were considered breast cancer-specific. Results: A total of 208 patients were enrolled in Phase I clinical trials, 168 in breast cancer-specific cohorts and 40 in all-comer trials. Patients on average were 56.9 years old (range 31-79), 98.6% (205/208) female, 1.4% (3/208) male, 57.2% ER+/Her2-, 30.1% ER-/Her2- and 11.1% Her2+. Patients received on average 2.1(range 0-10) prior lines of chemotherapy in the metastatic setting. Patients enrolled on Phase I clinical trials remained on study without progression on average for 138 days (CI 95%, 112.64 to 163.91). Patients enrolled on breast cancer-specific studies remained on study for 152 days (CI 95%, 120.66 to 182.56) compared to 82 days (CI 95%, 59.43 to 105.13) for those enrolled on all-comer trials, p< 0.05. Patients went off study for disease progression (83.17%), adverse events (7.69%), and other (9.14%), including withdrawal of consent. Conclusions: Patients with metastatic breast cancer previously treated with multiple lines of chemotherapy in the metastatic setting enrolled in Phase I clinical trials received clinical benefit from treatment that is favorable compared to historical controls of late-line chemotherapy. The majority of patients were treated on breast cancer-specific cohorts consistent with trends in Phase I trial design including more tumor specific cohorts.

A rapid method to estimate the value of genetic analysis of excised cancers: A comparison in the phase I setting.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 264-264
Author(s):  
Henry Jacob Conter ◽  
Razelle Kurzrock ◽  
Vancheswaran Gopalakrishnan ◽  
Leonard A. Zwelling
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Incremental Cost ◽  
Rapid Method ◽  
Cost Effective ◽  
Molecular Testing ◽  
Primary Concern ◽  
Phase I Clinical Trials ◽  
Genetic Sequencing ◽  
The Cost

264 Background: There is great interest in delivering personalized phase I clinical trials for patients. The value of this strategy will be determined by the increased benefit of the testing against the testing’s associated increased costs. We developed and employed a rapid method for determining this value in a cohort of metastatic melanoma patients who participated in phase I clinical trials at M.D. Anderson Cancer Center. Methods: The clinical parameter of benefit used was time to treatment failure (TTF) and the charges were those accrued by patients during their participation on the trial. Charge data were extracted from the MD Anderson business database. Clinical and charge data were employed in a simulation to compare two strategies: testing all patients' tumor for genetic aberrations or not. Results: In the subcohort of patients (N = 103) that were reviewed for this analysis, patients who underwent molecular testing experienced an increase in TTF of 2 months (4.2 versus 2, p=0.1) compared to those not tested, but this was not the primary concern of this study. Rather, the charges and clinical data allowed for a calculation of the value of the testing. The incremental cost-effectiveness ratio (ICER) of genetic sequencing was $49,103 per failure-free month. Ninety-four percent of the this incremental cost was due to the cost of staying on the phase I trial, with only 6% due to the cost of the genetic testing. If the cost of the genetic test was zero, the incremental ICER would still over $46,000 per failure-free month. Probabilistic sensitivity analysis demonstrated that the untested strategy was predicted to be the most cost-effective strategy with a willingness-to-pay (WTP) under $52,000 per failure-free month. The sequencing of tumors becomes 85% likely to be the most acceptable strategy by a WTP threshold of $360,000 per failure free month. Conclusions: These data suggest that making molecular testing cost effective requires reducing the costs of clinical research. This methodology is a way to make a determination of value, as well as attributable costs, which we believe will have to be made for each individual clinical setting.

scholarly journals Risk of serious toxicity in 1181 patients treated in phase I clinical trials of predominantly targeted anticancer drugs: the M. D. Anderson Cancer Center experience

2012 ◽  
Vol 23 (8) ◽  
pp. 1963-1967 ◽  
Author(s):  
J.J. Wheler ◽  
A.M. Tsimberidou ◽  
D.S. Hong ◽  
A. Naing ◽  
G.S. Falchook ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Anticancer Drugs ◽  
Cancer Center ◽  
Phase I Clinical Trials
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