1452P Use of the Pallia 10 score in patients enrolled in phase I trials at Gustave Roussy Cancer Center

6618 Background: Despite the growing number of clinical trials conducted in Asia and the unique pt demographic and molecular profile of endemic cancers, there is still lacking of studies examining the outcomes of pts on PIT. We examined the characteristics and outcomes of pts enrolled in phase I trials in National Cancer Center Singapore (NCCS). Methods: We reviewed 296 pts enrolled in PIT from 2004-2012 to identify factors that predicted for 90-day mortality and OS. Logistic regression model and Cox proportional hazard model assessed factors associated with 90DM and OS, respectively. The discriminative ability of the RMH prognostic score (LDH, no of met sites, albumin) and the final multivariate Cox model derived in Asian pts was evaluated using Harrell’s concordance index (c-index), and that for the logistic model was based on area under ROC curve (AUC). Internal validation was performed based on simulated data via bootstrapping. Results: Median age 60 (23-85), M:F (65/35%). The commonest cancer type thoracic (56%), GI (24%), head and neck (12%). 57% pt had comorbidities, commonest diabetes (16.6%) and hepatitis B (11.1%). Median no of lines of treatment 2. 20% of pts had known mut status. 15% pts survived less than 90 days from start of trial. Median OS was 9.6 m (95CI 7.8-11.2 m). Based on the RMH prognostic model, pts with score of 0 to 1 had a superior OS (median OS = 12.9 m) compared to those with score of 2 to 3 (OS = 5.7 m) (p < 0.001). The c-index for the RMH prognostic score was 0.64. On univariate analysis, alb<35,LDH>ULN, ≥3 met sites, low BMI, ECOG>0, Na<135,plt>440, Hb<12 and ≥3 lines of chemo were negative prognostic factors. On multivariate analysis, reduced model selection techniques identified alb<35, LDH>ULN, ≥3 met sites, and ≥ 3 prior lines of chemo as independent negative predictors of OS with a bias-corrected of 0.69. For 90DM, we developed a risk normogram based on ECOG, WBC, Na and Hb as continuous predictors with bias-corrected AUC 0.78. Conclusions: We have developed a novel NCCS normogram to predict for 90DM for PIT. The RMH prognostic score can be improved upon with the addition of number of prior lines of chemotherapy, underscoring the importance of early access to phase I trials.

Download Full-text

Use of the Pallia 10 score in patients enrolled in phase I trials at Gustave Roussy Cancer Center.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.23 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 23-23

Author(s):

Kaissa Ouali ◽

Christine Mateus ◽

Ariane Laparra ◽

Elena Pavliuc ◽

Patricia Martin Romano ◽

...

Keyword(s):

Palliative Care ◽

Prognostic Factors ◽

Phase I ◽

Subsequent Treatment ◽

Palliative Care Unit ◽

Cancer Center ◽

Phase I Trials ◽

Double Blind ◽

Palliative Care Consultation ◽

Systemic Treatments

23 Background: Early phase clinical trials usually include patients (pts) with advanced disease who have failed to standard therapies. Early palliative care (EPC) for these pts has shown to improve quality of life and even survival. Pallia 10 score (from 1 to 10) is a tool developed by the French Palliative Care Society to identify the best time to introduce palliative care. Methods: We assessed the Pallia 10 score and other prognostic factors (age, ECOG, Royal Marsden Hospital (RMH) score, LDH and albumin levels, number (nb) of prior systemic treatments and metastatic sites) in pts enrolled in phase I trials (P1CT) prospectively during 2 periods of time (cohort 1 (C1) and 2 (C2)). A double-blind assessment of the Pallia 10 score was done during 15 days by a member of the palliative care unit in C2. A Pallia 10 > 3 motivated a dedicated palliative care consultation. Results: From 01/07/2018 to 01/11/2018 (C1) and from 01/12/2020 to 16/04/2021 (C2), a total of 85 pts were assessed in C1 and 302 in C2. Gastro-intestinal (23%), hematological (14%) and lung (11%) cancer were the most frequent tumor types. Pallia 10 score and prognostic factors were similar between both cohorts (Table). On C1 and C2, 12% and 4% of pts had a dedicated palliative consultation with median time of referral of 18 and 2 months (m) after the P1CT onset (p = 0.003), with a median Pallia 10 score of 1.5 and 2 (p = 0.65), respectively. Overall, 75% and 76% of pts in C1 and C2 were still alive beyond 3m after discontinuation of the P1CT (p = 0.91), followed by at least one subsequent treatment in 56% and 54% of pts. In C2, assessment of Pallia 10 score was significantly different between palliative care physician (median 5, range 3-8), phase I physician (median 1, range 1 -6) and phase I nurse (median 3, range 1-8) (p < 0.001). Conclusions: Only a few patients included in P1CT were referred to the palliative care unit. Median Pallia 10 score was low when assessed by the phase I physician which suggests the need for a better tool to implement EPC in clinical practice and trials.[Table: see text]

Download Full-text

Design and results of phase I cancer clinical trials: three-year experience at M.D. Anderson Cancer Center.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.1.287 ◽

1996 ◽

Vol 14 (1) ◽

pp. 287-295 ◽

Cited By ~ 71

Author(s):

T L Smith ◽

J J Lee ◽

H M Kantarjian ◽

S S Legha ◽

M N Raber

Keyword(s):

Phase I ◽

Phase Ii ◽

Alternative Methods ◽

Recommended Dose ◽

Cancer Center ◽

Phase I Trials ◽

Conducting Phase ◽

Number Of Patients ◽

Standard Design ◽

Baseline Information

PURPOSE Alternatives to the standard design for conducting phase I trials are proposed with increasing frequency. This study was undertaken to determine how phase I trials are currently conducted and to provide a basis for evaluation of evolving methodology. SUBJECTS AND METHODS All published phase I trials from a single institution over a 3-year period were reviewed to determine the method of selection of the recommended dose for a phase II trial of a new agent, type and extent of toxicity, number of patients treated at the recommended dose, and clinical response. RESULTS All 23 published trials used the standard method of entering cohorts of patients at increasing dose levels and observing toxic effects to determine the dose recommended for phase II study. Among 610 patients, 26% were treated at or within 10% of the recommended dose and 35% were treated with less than 50% of the recommended dose or on a trial that yielded no recommended dose. Among 18 trials using agents previously tested in humans, fewer patients were treated at much less than the recommended dose. For trials in which myelosuppression was dose-limiting, the estimated probability of serious myelosuppression associated with the recommended dose ranged from 23% to 66%. Nineteen patients (3%) responded to therapy. CONCLUSION This summary of phase I trials recently conducted at M.D. Anderson Cancer Center confirms the need for alternative methods, provides baseline information against which alternatively conducted trials can be compared, and demonstrates some practical clinical trial issues not generally considered when alternative methods are proposed.

Download Full-text

Outcomes of patients ≥65 years old with advanced cancer treated on phase I trials at MD ANDERSON CANCER CENTER

International Journal of Cancer ◽

10.1002/ijc.30417 ◽

2016 ◽

Vol 140 (1) ◽

pp. 208-215 ◽

Cited By ~ 5

Author(s):

Ishwaria M. Subbiah ◽

Jennifer J. Wheler ◽

Kenneth R. Hess ◽

David S. Hong ◽

Aung Naing ◽

...

Keyword(s):

Phase I ◽

Advanced Cancer ◽

Cancer Center ◽

Phase I Trials ◽

Md Anderson

Download Full-text

Complementary and Alternative Medicine Use by Patients Enrolled Onto Phase I Clinical Trials

Journal of Clinical Oncology ◽

10.1200/jco.2004.03.121 ◽

2004 ◽

Vol 22 (23) ◽

pp. 4810-4815 ◽

Cited By ~ 91

Author(s):

Grace K. Dy ◽

Lishan Bekele ◽

Lorelei J. Hanson ◽

Alfred Furth ◽

Sumithra Mandrekar ◽

...

Keyword(s):

Alternative Medicine ◽

Phase I ◽

Complementary And Alternative Medicine ◽

Demographic Data ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Phase I Trials ◽

Phase I Clinical Trials ◽

Cam Use ◽

Complementary And Alternative

Purpose To describe the prevalence, clinical characteristics, and pattern of use of complementary and alternative medicine (CAM) in patients enrolled onto phase I trials. Patients and Methods Questionnaires were administered to 108 patients with advanced malignancies enrolled onto phase I chemotherapy trials at the Mayo Clinic Comprehensive Cancer Center (Rochester, MN). CAM was classified into two modalities, pharmacologic and nonpharmacologic. Clinical and demographic data, including age, sex, and prior cancer treatment, were subsequently obtained from patient charts and examined for any correlation with CAM use, using χ2 analysis. Results One hundred two survey forms were returned. Among respondents, 88.2% (90 of 102) had used at least one CAM modality; 93.3% (84 of 90) and 53.3% (48 of 90) had used pharmacologic and nonpharmacologic CAM, respectively; and 46.7% (42 of 90) used both modalities. Vitamin and mineral preparations constituted 89.3% (75 of 84) of all pharmacologic CAM used. Intake was highest for vitamins E (48.8% [41 of 84]) and C (38.1% [32 of 84]), and 71.4% (60 of 84) of respondents took nonvitamin/mineral agents. Green tea (29.8% [25 of 84]), echinacea (13.1% [11 of 84]), and essiac (9.5% [8 of 84]) were the most popular. Prayer and spiritual practices were the most commonly used nonpharmacologic CAM, accounting for 52.1% (25 of 48). Chiropractors, the most frequently visited nontraditional medicine practitioners, were consulted by only 10% (9 of 90) of those who practiced CAM. Both CAM modalities were used more frequently by women (53.5% [23 of 43]) than men (40.4% [19 of 47]). Conclusion CAM use is common among patients in phase I trials and should be ascertained by investigators, because some of the agents used may interact with investigational agents and affect adverse effects and/or efficacy.

Download Full-text

Use of the PALLIA 10 Score in Patients Enrolled in Phase I Trials at Gustave Roussy Cancer Center

10.21203/rs.3.rs-1141116/v1 ◽

2022 ◽

Author(s):

Kaïssa Ouali ◽

Cristine Mateus ◽

Arianne Laparra ◽

Elena Pavliuc ◽

Patricia Martin-Romano ◽

...

Keyword(s):

Palliative Care ◽

Prognostic Factors ◽

Phase I ◽

Palliative Care Unit ◽

Cancer Center ◽

Phase I Trials ◽

Double Blind ◽

Early Palliative Care ◽

Palliative Care Consultation ◽

Systemic Treatments

Abstract Background Early phase clinical trials usually include patients with advanced disease who have failed standard therapies. Early palliative care for these patients has shown to improve quality of life and even survival. PALLIA 10 score (ranging from 1 to 10) is a tool developed by the French Palliative Care Society to identify the best time to introduce palliative care. Methods We assessed the PALLIA 10 score and other prognostic factors (age, ECOG, Royal Marsden Hospital (RMH) score, LDH and albumin levels, number of prior systemic treatments and metastatic sites) in patients enrolled in phase I trials at Gustave Roussy Cancer Center prospectively during 2 periods of time (cohort 1 (C1) and 2 (C2)). A double-blind assessment of the PALLIA 10 score was done during 15 days by a member of the palliative care unit in C2. A PALLIA 10 > 3 motivated a dedicated palliative care consultation. Results From July 1st 2018 to November 1st 2018 (C1) and from December 1st 2020 to April 16th 2021 (C2), a total of 86 patients were assessed in C1 and 302 in C2. No difference was observed between the two cohorts regarding prognostic factors. Median PALLIA 10 was also similar and very low (median 1, range 1-5 in C1 and 1-8 in C2). On C1 and C2, 12% and 5% of patients had a dedicated palliative consultation. Overall, 77% and 74% of patients in C1 and C2 were still alive beyond 3 months after discontinuation of the trial (p=0.78), followed by at least one subsequent treatment in 63% and 70% of pts. In C2, assessment of PALLIA 10 score was significantly different between palliative care physician (median 5, range 3-8), phase I physician (median 1, range 1 -6) and phase I nurse (median 3, range 1-8) (p<0.001). Conclusion Only a few patients included in phase I clinical trial were referred to the palliative care unit. Median PALLIA 10 score was low when assessed by the phase I physician which suggests the need for a better tool to implement early palliative care in clinical practice and trials.

Download Full-text

Outcome analyses of patients with metastatic cervical cancers in a phase I clinic.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e13534 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e13534-e13534

Author(s):

Ming-Mou Hou ◽

Xiaochun Liu ◽

Jennifer J. Wheler ◽

Aung Naing ◽

David S. Hong ◽

...

Keyword(s):

Phase I ◽

Cell Carcinoma ◽

Phase I Trial ◽

High Rate ◽

Prognostic Scores ◽

Cancer Center ◽

Phase I Trials ◽

Pik3ca Mutations ◽

Cervical Cancers ◽

Md Anderson

e13534 Background: Patients with metastatic cervical cancers have a poor prognosis and few effective therapies available. Thus, access to a phase I trial may provide a viable option. Methods: Outcomes of 54 consecutive patients with metastatic cervical cancers seen in a phase I clinic at MD Anderson Cancer Center from 1/1/2006 to 12/31/2012 were reviewed in accordance with the MD Anderson IRB guidelines. Results: The 54 patients included Caucasians (n=34, 63%), Hispanics (n=9, 17%), African Americans (n=7, 13%), and others (n=4, 7%). Pathological diagnoses were squamous cell carcinoma (n=33, 60%), adenocarcinoma (n=12, 22%), adenosquamous (n=3, 6%), poorly differentiated carcinoma (n=2, 4%), small cell carcinoma (n=2, 4%), clear cell carcinoma (n=1, 2%), and melanoma (n=1, 2%). Initial staging was as follows: I (n=16, 30%), II (n=11, 20%), III (n=11, 20%), and IV (n=16, 30%). Prior treatment included surgery (n=23, 43%), radiotherapy (n=41, 76%), and systemic chemotherapy (n=54, 100%) including one regimen (n=30, 55%), two (n=15, 28%) and more (n=9, 17%). At their initial visit to the phase I clinic, the median age was 47 years. The majority of patients had ECOG PS 0-1 (n=45, 83%), and MDACC prognostic scores 0-1 (n=48, 89%). Almost all the 54 referred patients were enrolled into a phase I trial (n=52, 96%). Initial phase I trials these patients had received led to one CR, five PR, and 12 SD ≥ 6 months (CR/PR/SD≥6 months=35%). Of the patients who progressed on their first protocols, 11 patients (21%) were enrolled into a second protocol, leading to 36% of PR/SD≥6 months (n=4). Among those enrolled into a third (n=4) and a fourth (n=1) study, no CR/PR/SD≥6 months was achieved. The median overall survival in these 54 referred patients was 10.6 months. Among 36 patients who underwent molecular marker studies, 15 were found to harbor PIK3CA mutations and/or PTEN loss (42%) and achieved 60% of CR/PR/SD≥6 months (3 PR and 6 SD≥6 months). Conclusions: Aberrant PI3K pathway was frequently identified in advanced cervical cancers, and the high rate of CR/PR/SD≥6 months was observed in these patients treated under a phase I trial, suggesting that phase I trials, especially mutation matched regimens, may provide potential benefits to these patients.

Download Full-text

Phase I clinical trials as a therapeutic option for patients with metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5073 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5073-5073

Author(s):

Andrew W Hahn ◽

Omar Alhalabi ◽

Funda Meric-Bernstam ◽

Aung Naing ◽

Eric Jonasch ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Phase I ◽

Checkpoint Inhibitors ◽

Therapeutic Option ◽

Phase I Clinical Trial ◽

Cancer Center ◽

Phase I Trials ◽

Phase I Clinical Trials ◽

Entire Cohort

5073 Background: Immune checkpoint inhibitors, multi-kinase VEGF agents, and mTOR inhibitors are approved for mRCC. Due to the overlapping mechanisms of action of the twelve approved therapies for mRCC, select patients are referred for phase I clinical trials after progression on multiple lines of treatment. We sought to evaluate the efficacy of phase I trials in patients with mRCC. Methods: Patients with all histologies of mRCC were included if they received treatment on a phase I clinical trial at MD Anderson Cancer Center. Baseline clinical characteristics and outcomes data were retrospectively collected. The historical control was a study of 1112 patients with mRCC who received third-line treatment in the IMDC database (PMID: 27318422). Time to event endpoints were calculated using Kaplan-Meier methods. Hazard ratios (HR) were calculated using the Cox proportional hazard model. Results: Between 2014 and 2019, there were 106 cases where 82 patients with mRCC were enrolled in a phase I clinical trials (40 unique trials). 30% (32/108) of the cases were in patients with non-clear cell RCC (nccRCC), and the most prevalent nccRCC histologies were papillary (n = 7) and renal medullary carcinoma (n = 7). The median number of prior systemic therapies was 2 (range 0-9). Across the entire cohort, median PFS was 5.9 months (m), median OS was 31.2 m, and the ORR was 23% (Table). In patients who received at least two prior lines of therapy (n = 70), the median PFS was 4.8 m and median OS was 24.9 m. In patients with metastatic nccRCC, median OS, PFS, and ORR were numerically lower, but statistically did not contradict the supposition that these outcomes did not differ from ccRCC (Table). Conclusions: In the largest pooled phase I clinical trial experience for patients with mRCC, phase I trials may have therapeutic value when compared to historical controls, where median PFS was 3.9 m, median OS was 12.4 m, and ORR was 10.5%. Patients with all histologies of mRCC may derive clinical benefit from phase I clinical trials, yet patients with ccRCC had numerically better outcomes. Patients with mRCC should be considered for phase I clinical trials. [Table: see text]

Download Full-text