Phase I trial of docetaxel (D) plus samarium153 (Sm 153) in patients (pts) with hormone refractory prostate cancer (HRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15547-15547 ◽  
Author(s):  
V. J. Sinibaldi ◽  
M. A. Carducci ◽  
T. DeWeese ◽  
J. Weber ◽  
R. Drew ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase I ◽  
Phase I Trial ◽  
Performance Status ◽  
Hepatic Function ◽  
Great Promise ◽  
Significant Activity ◽  
Ecog Performance Status ◽  
Preclinical Data ◽  
Hormone Refractory

15547 Background: Bone targeted approaches hold great promise for improving outcomes in HRPC. Docetaxel (D) and samarium 153 (Sm153 ) have individually demonstrated a clinical benefit and preclinical data strongly support biological synergism in HRPC. Preclinical data suggests that 24 hour after a dose of D, there is maximum G2M arrest. This results in the accumulation of cells in the most radiosensitive phase of the cell cycle. This phase I trial was designed to evaluate toxicity and preliminary efficacy of combined D and Sm153 administered sequentially in advanced HRPC. Methods: HRPC pts progressing after anti-androgen withdrawal; = 2 prior chemotherapy regimens; acceptable bone marrow, renal and hepatic function were eligible. Planned D treatment in 4 cohorts (N=3/cohort) includes: Cohort 1: D 50mg/m2 IV on days 1, 22, 91, and 112; cohort 2: D 75mg/m2 IV on days 1 and 22 followed by 50mg/m2 IV on days 91 and 112; cohort 3: D 75mg/m2 IV on days 1 and 22 followed by 75mg/m2 IV on days 91 and 112; cohort 4: D 75 mg/m2 IV on days 1, 22, 42, 91, 112, and 133. Sm 153 (1.0 mi/Kg) is administered IV days 2 and 92 of each cycle. Cycles are repeated Q 12 wks (max 2 cycles). The endpoint for this trial is dose limiting toxicity and maximal tolerated dose. Results: From 5/11/05 - 1/7/07 ten pts were enrolled. Median: age 69.5 yrs (range 58–76), ECOG performance status 1 (range 0–1), baseline PSA 76.65 ng/ml (range 9.6–1064 ng/ml ), prior hormonal manipulations 3 (range1–6). Three pts had prior taxotere and 3 pts had prior palliative RT. All had bone metastases and 2 also had soft tissue disease. Five pts completed 2 cycles of treatment as planned. Five pts had 1 cycle (one pt is on treatment, 3 pts had PD and 1 had prolonged grade 1 thrombocytopenia =3 wks). Nine of 10 pts had reversible grade 3 / 4 neutropenia (1 pt had reversible episode of neutropenia with fever). Seven of 7 symptomatic pts had improvement in pain. Four of 10 of pts had a 50 % decline in PSA level lasting = 4 weeks; no soft tissue disease responses. Conclusions: Our preliminary data suggest that Q 3 wk D and Q 3 month Sm153 may be administered simultaneously at full doses in extensively pretreated HRPC pts, with acceptable toxicity and significant activity. This study is supported by a grant from sanofi- aventis and Sm153 is provided by Cytogen. No significant financial relationships to disclose.

Phase I experience with c-MET inhibitor XL880 administered orally to patients (pts) with solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3526-3526 ◽  
Author(s):  
J. P. Eder ◽  
E. Heath ◽  
L. Appleman ◽  
G. Shapiro ◽  
D. Wang ◽  
...  
Keyword(s):  
Phase I ◽  
Phase 1 ◽  
Performance Status ◽  
Vegf Receptor ◽  
Significant Activity ◽  
Phase Ii Trials ◽  
Ecog Performance Status ◽  
Correlative Studies ◽  
Tumor Biopsies

3526 Background: XL880 is a sub-nM inhibitor of the hepatocyte growth factor receptor (Met) and VEGF receptor family with low in vitro nM inhibition of PDGFRβ, KIT, FLT3, Tie-2 and Ron. Methods: The safety of XL880 was evaluated in two phase 1 studies. XL880 was administered mass-based on a 5 days on / 9 days off schedule (study 1) or as a fixed daily dose (study 2). Inclusion criteria include ECOG performance status = 2, adequate liver, cardiac, and renal function and no brain metastases. Tumor response is assessed every 8 wks by RECIST criteria. Pharmacokinetics, pre and post treatment tumor biopsies and plasma markers of angiogenesis (VEGF, sVEGFR and Ang2) were collected. Results: To date, 51 pts have been dosed in studies 1 & 2. In study 1, dose limiting toxicities (DLT) included reversible Gr3 elevations of lipase, hepatic transaminases and proteinuria. The maximum tolerated dose (MTD) was 3.6 mg/kg. In study 2, the MTD has not been defined. Common adverse events include hypertension and fatigue with loss of concentration. In study 1, 5 of 40 pts had partial responses (2+ -12+ months[m]), 3 pts had minimal responses and 8 pts had stable disease (SD) > 3 m. In study 2, 5 of 8 evaluable pts had SD > 3 m (4 ongoing) and 3 are too early to evaluate. Correlative studies in tumor biopsies show marked inhibition of phospho (p)-met, p-RON, p- ERK, p-AKT and increased apoptosis at less than the MTD. Patients in study 2 pts showed lower XL880 Cmax values with consistent mean concentrations (Css)compared with study 1 MTD pts. Css levels are reached in 15 d. Conclusions: XL880 as daily oral or 5 day on / 9 day off administration is generally well tolerated for > 1 year, although hypertension is nearly universal but manageable. XL880 has demonstrated substantial phase I antitumor activity with both dosing regimens. Correlative studies indicate significant activity against Met and Ron signaling. Enrollment continues on study 2. Phase II trials in gastric cancer and head and neck cancer will begin soon. No significant financial relationships to disclose.

A phase I trial of bexarotene and docetaxel in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13085-13085
Author(s):  
M. J. Pishvaian ◽  
K. Firozvi ◽  
J. J. Hwang ◽  
J. L. Marshall ◽  
P. Ramzi ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase I Trial ◽  
Performance Status ◽  
Fixed Dose ◽  
Ecog Performance Status ◽  
Radiation Recall ◽  
Serum Triglycerides ◽  
Experienced Grade ◽  
Grade Iii

13085 Background: Retinoids have been used to treat a wide variety of malignancies. Bexarotene is a synthetic retinoid that binds preferentially to the RXR subclass of retinoid receptors. In the initial phase I trial of bexarotene, a subset of patients with non-small cell lung cancer (NSCLC) had prolonged stabilization of disease and survival. In vitro evidence suggests that the effects of retinoids may be enhanced when used in conjunction with taxanes. This is a phase I trial designed to determine the maximum tolerated dose of docetaxel in combination with a fixed dose of bexarotene. Methods: Patients with pathologically confirmed solid tumors for whom no standard therapies exist, who have an ECOG performance status ≤2, adequate organ function and normal serum triglycerides were eligible. Each cycle was 4 weeks long. Oral bexarotene was given at 400 mg/m2 daily. Docetaxel was given weekly for 3 out of 4 weeks at two dose levels, 25 or 30 mg/m2, for up to 6 cycles. For patients exhibiting disease stabilization or response, treatment with bexarotene was continued until disease progression. Restaging studies were performed after every 2 cycles. Results: To date 10 patients have been enrolled, half of whom had NSCLC - 7 male, mean age = 61 (range 37–73), 100% PS = 0 or 1. 29 cycles were completed (range 1 to 8). 7 patients have been treated at 25 mg/m2 and 3 at 30 mg/m2 of docetaxel. Hypothyroidism, hypertriglyceridemia, and fatigue were common but generally mild. Two patients experienced grade III fatigue, and 1 each experienced grade III hypertriglyceridemia, neutropenia, and cough. There were no grade IV toxicities. Two patients were taken off study because of non-fatal radiation recall pneumonitis that was controlled with steroids. In this heavily pretreated population, of 8 patients assessable for response, 5 had stable disease for at least 2 cycles. One patient with NSCLC had a partial response that persisted for 6 cycles. Conclusions: Bexarotene and docetaxel (at a minimum of 25 mg/m2) can be safely coadministered. Care should be taken in patients who have been previously irradiated. Enrolment and dose escalation for the phase I trial is still ongoing. A phase II trial of the combination as second line therapy in NSCLC is planned. [Table: see text]

A phase I trial of concurrent chemoradiotherapy (cCRT) with the conventional administration of docetaxel (D) and cisplatin (P) for dry-stage III non-small cell lung cancer (NSCLC) (JCOG9901DI)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7549-7549
Author(s):  
N. Hida ◽  
S. Tsujimura ◽  
T. Fujii ◽  
K. Naoki ◽  
H. Kunikane ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Recommended Dose ◽  
Stage Iii ◽  
Ecog Performance Status ◽  
Full Dose ◽  
Level 2

7549 Background: In cCRT for locally advanced NSCLC, full dose chemotherapy with a new agent plus a platinum doublet is considered to have unacceptable toxicities. Consequently, weekly or split chemotherapy doses are often used. However, cCRT plus conventional regimens are expected to enhance systemic effects. This phase I trial aimed to establish the MTD of cCRT plus conventional administration of DP (conv-DP). Methods: Unresectable stage III NSCLC patients (pts) (<70 years) with ECOG performance status 0–1 and adequate organ function were eligible. Pts received 60 Gy in 30 fractions by once daily radiotherapy. Concurrent P (day1; 60 mg/m2 at levels 1–3, 80 mg/m2 at level 4) and D (day1; 30 mg/m2 at level 1, 40 mg/m2 at level 2, 50 mg/m2 at levels 3–4) were given every 4 weeks for at least 2, and up to 4 courses. DLT was defined as either Gr3/4 febrile neutropenia, Gr4 neutropenia lasting ≥ 4 days, Gr4 thrombocytopenia, Gr2 pneumonitis or any Gr3 non-hematological toxicities except for nausea, vomiting and alopecia. Results: Eighteen pts were enrolled from 06/1999 to 05/2006: 6 pts at levels 2 and 4, 3 pts at levels 1 and 4; 13 males; median age 60 years (range 43–70); stage IIIA/IIIB 5/13; histology Ad/Sq/Large 9/7/2. DLTs were observed for 3 pts at level 2 (D40/P60): Gr4 pneumonitis at level 3(D50/P60), Gr3 cerebral infarction and Gr3 atrial fibrillation. Although 3 cases were added at these levels, tolerability for each level was cleared, as DLTs occurred for ≤ 2 pts among 6. MTD was not detected, even at the highest dose (D50/P80). However, dose escalation was stopped, as D60/P80 was the recommended dose for chemotherapy alone in Japan. Radiotherapy (60 Gy) was completed for 15 pts. Seventeen pts received more than 2 courses of chemotherapy. No Gr3/4 esophagitis or severe hematologic toxicities were observed. Objective response rate was 89% and 1-yr survival rate was 55%. Conclusions: The recommended dose in this regimen was D50/P80, which was near the full dose for conv-DP. Based on these promising results, we are planning a phase II trial to evaluate the efficacy and toxicity of this cCRT with conv-DP therapy. No significant financial relationships to disclose.

Phase I Trial of Oral Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Combination with Bortezomib in Patients with Advanced Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1172-1172 ◽  
Author(s):  
Donna M. Weber ◽  
Sundar Jagannath ◽  
Amitabha Mazumder ◽  
Ronald Sobecks ◽  
Gary J. Schiller ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Phase I ◽  
Stable Disease ◽  
Phase I Trial ◽  
Performance Status ◽  
Single Agent ◽  
Primary Objective ◽  
Combination Regimen ◽  
Ecog Performance Status

Abstract Background: Vorinostat is a histone deacetylase inhibitor that has demonstrated antiproliferative and proapoptotic activity alone and in combination with the proteasome inhibitor bortezomib in preclinical multiple myeloma (MM) models. In a Phase I study, vorinostat also demonstrated modest single agent activity in patients (pts) with relapsed or refractory MM. Patients and Methods: We conducted a Phase I trial of oral vorinostat (200 mg bid or 400 mg daily × 14 days (d1–14) in combination with bortezomib 0.7 or 0.9 mg/m2 i.v. on d 4, 8, 11 and 15 or 0.9, 1.1, or 1.3 mg/m2 i.v. on d 1, 4, 8 and 11. Cycles were repeated every 21 d for a maximum of 8 cycles until progressive disease (PD) or intolerable toxicity. Pts with active relapsed or refractory MM who had not received bortezomib in the preceding 3 months and with adequate hematologic, hepatic, and renal function, and ECOG performance status of 0–2 were eligible. The primary objective was to determine the maximum tolerated dose (MTD). Activity (utilizing EBMT criteria) and safety of the combination regimen were also assessed. Results: Twenty pts have been enrolled: median age, 61 years (range 52–76), median number prior systemic therapies, 3 (range 1–14), prior therapy with bortezomib (4 pts). Eighteen pts have received ≥ 1 dose and were evaluable for safety as of 7/1/07. One pt (cohort 3) experienced a dose-limiting toxicity (DLT, Table). The MTD has not been reached. The most common drug-related toxicities of any grade were nausea (56%), thrombocytopenia (50%), diarrhea (39%), vomiting (39%), fatigue (39%), and anemia (22%). Grade ≥ 3 drug-related adverse events were thrombocytopenia (33%, none associated with bleeding), peripheral neuropathy (11%), neutropenia (11%, none associated with fever), diarrhea (6%), diverticulitis (6%), fatigue (6%), increased AST (6%), memory changes (6%), nausea (6%), vomiting (6%), and upper respiratory infection (6%). Eight pts discontinued treatment, 3 due to PD and 5 due to adverse experiences [fatigue (2), nausea (2), diverticulitis (1)]. Of 17 evaluable pts for efficacy, all had measurable response or stable disease; 4 had a partial response, 2 had a minimal response, and 11 stable disease. Among 3 evaluable pts previously treated with bortezomib, 1 achieved a partial response and 1, minimal response. Pts at the highest dose level were not yet evaluable for response. Conclusion: Although accrual continues to determine the MTD, the combination of vorinostat and bortezomib is well tolerated and effective in this group of heavily pretreated pts with refractory/relapsed MM. Table Cohort Vorinostat Dose (mg) Bortezomib Dose (mg/m2) N # of Cycles DLTs Best Response MR = minimal response; NE = not evaluable; PR = partial response; SD = stable disease. *Days 4, 8, 11 and 15. †Days 1, 4, 8 and 11. ‡Treatment cycle in progress. 1 200 0.7* 3 3, 3, 14 - SD (2), PR 2 200 0.9* 3 4, 5, 6 - SD (2), PR 3 400 0.9† 6 2, 3, 5, 6, 6, 6 Transient AST elevation SD (3), MR, PR (2) 4 400 1.1† 5 3, 3, 4, 5, 11 - SD (4), MR 5 400 1.3† 3 1‡, 1‡, 2 - NE (3)

Clinical outcomes of patients with breast cancer in a phase I clinic: The M. D. Anderson Cancer Center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1054-1054
Author(s):  
J. J. Wheler ◽  
A. Tsimberidou ◽  
S. Moulder ◽  
M. Cristofanill ◽  
D. Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Clinical Outcomes ◽  
Median Duration ◽  
Phase I Trial ◽  
Performance Status ◽  
Metastatic Breast ◽  
Ecog Performance Status

1054 Background: Patients with metastatic breast cancer refractory to standard therapy are eligible for phase I trials. We assessed prognostic factors and clinical outcomes for patients with breast cancer in a phase I clinic focused on targeted agents. Methods: We reviewed the medical records of sequential patients with metastatic breast cancer who presented to our phase I clinic from September 2004 to May 2008. We assessed the relationship between overall survival and patients’ demographic and clinical characteristics using both univariate and multivariate (Cox proportional hazard model) analyses. Results: Ninety-two patients were identified with median age of 53 years (range 28 to 83 years). The median number of prior therapies was 5 (range 1 to 16). The median follow-up of surviving patients is 7.4 months. The median overall survival is 6.7 (95% CI: 5.2, 9.7) months. In univariate analysis, factors predicting shorter survival were elevated Ca-125 (p = 0.001) (Ca27.29 was not significant), albumin < 3.5 g/dL (p = 0.002), worsening ECOG performance status (p = 0.004), absolute neutrophil count < 7.3 x 109/L (p = 0.004), ≥ 10 prior treatment regimens (p = 0.008), ≥ 5 prior chemotherapy-only regimens (p = 0.008), body mass index (BMI) < 25 (p = 0.018), and elevated platelet counts (p = 0.007). In multivariate analysis, independent factors predicting shorter survival were ≥10 prior treatments (vs. <10 prior treatments) (HR = 3.27; 95% CI 1.37, 7.81; p = 0.0077), ECOG performance status 2–3 (vs. 0–1) (HR = 2.92; 95% CI 1.28, 6.66; p = 0.01), and albumin < 3.5 g/dL (vs. > 3.5g/dL) (hazard ratio [HR] = 2.88; 95% CI; 1.41, 5.89; p = 0.004). Of 78 patients treated on a first phase I trial, 14 (18%) demonstrated stable disease (SD), with a median duration of 18 weeks (range 10–25). Of those 19 patients treated on a second phase I trial, 6 (32%) had SD with a median duration of 12 weeks (range 8–17). Two of 4 (50%) patients treated on a third phase I trial had SD with a median duration of 20 weeks (range 16–24). Conclusions: Patients with metastatic breast cancer referred for our phase I studies had a median survival of 6.6 months. In this preliminary analysis, independent factors predicting shorter survival were ≥ 10 prior treatments, worsening ECOG performance status and low albumin levels. No significant financial relationships to disclose.

Phase I trial of daily lenalidomide and docetaxel given every three weeks in patients with advanced solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3570-3570 ◽  
Author(s):  
S. L. Sanborn ◽  
M. Cooney ◽  
J. Gibbons ◽  
J. Brell ◽  
P. Savvides ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase I Trial ◽  
Performance Status ◽  
Unknown Primary ◽  
Hematologic Toxicity ◽  
Advanced Solid Tumors ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Grade 3

3570 Background: Lenalidomide is a potent anti-angiogenic and immune modulating agent. This phase I trial of docetaxel and lenalidomide was undertaken to evaluate the maximal tolerated dose (MTD), dose-limiting toxicity (DLT), and secondarily, any tumor response for this novel combination. Methods: Patients with advanced solid tumors with adequate organ function were eligible. Lenalidomide was given orally days 1–14, and docetaxel was administered intravenously on day 1 of each 21-day cycle. DLT was defined as grade 3 or higher non-hematologic toxicity, grade 4 neutropenia with fever, and grade 4 anemia or thrombocytopenia. Results: Nineteen patients, 14 male and 5 female, with tumor types including prostate (7), sarcoma (3), head and neck (2), pancreatic, colon, melanoma, adenocarcinoma of unknown primary, gastric, bladder, and GIST have been enrolled. ECOG performance status was zero (10 patients) or one (9 patients). The median age was 59 years (range 35 to 86). Fourteen patients had zero or one prior treatment regimens (range 0 to 6). A total of 64 cycles have been administered (range 1 to 12). In the first nine evaluable patients, eight (89%) had grade 3 or 4 neutropenia. Docetaxel 75 mg/m2 given every 3 weeks with lenalidomide 5 mg on days 1–14 exceeded the MTD due to one grade 3 nausea/vomiting and one grade 4 neutropenia with fever. After the addition of pegfilgrastim on day 2, there has not been any neutropenia in the subsequent seven evaluable patients. Other grade 3 and 4 toxicities included leukopenia (31%), lymphopenia (19%), as well as nausea, vomiting, fatigue, anemia, infection, hyponatremia, and hypokalemia (6% each). Seven patients (44%) have had stable disease (range 3 to 12 cycles). One prostate cancer patient experienced a >95% reduction of PSA. Enrollment is ongoing and the current dose level is docetaxel 75 mg/m2, lenalidomide 10 mg days 1–14, and pegfilgrastim on day 2. Conclusions: The toxicity evaluation is ongoing. This trial will provide the MTD of docetaxel 75 mg/m2 given every 3 weeks with lenalidomide on days 1–14 in combination with pegfilgrastim support to avoid neutropenia. No significant financial relationships to disclose.

604: A Phase I Trial of Vaccination of Personalized Peptides for HLA-A2/A24 Positive Patients with Hormone-Refractory Prostate Cancer

2007 ◽  
Vol 177 (4S) ◽  
pp. 202-202
Author(s):  
Hirotsugu Uemura ◽  
Motoyoshi Tanaka ◽  
Shigeya Uejima ◽  
Takafumi Minami ◽  
Kiyohide Fujimoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies

2020 ◽  
Vol 7 (2) ◽  
pp. 125-132
Author(s):  
Karen A. Gelmon ◽  
Christian Kollmannsberger ◽  
Stephen Chia ◽  
Anna V. Tinker ◽  
Teresa Mitchell ◽  
...  
Keyword(s):  
Phase I ◽  
Salvia Miltiorrhiza ◽  
Performance Status ◽  
Parent Drug ◽  
Maximum Tolerated Dose ◽  
Ecog Performance Status ◽  
Advanced Malignancies ◽  
Gi Toxicity ◽  
Adequate Organ Function ◽  
Recommended Phase Ii Dose

Background/Objective: With the increasing interest in natural products, a phase I openlabel study of OMN54 (Aneustat™) in patients with advanced malignancies was initiated to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent, combining three Chinese botanicals; Ganoderma lucidium, Salvia miltiorrhiza and Scutellaria barbata. Methods: Eligible patients (pts) were >18 years of age with advanced solid tumors, able to swallow oral capsules, ECOG performance status < 2, measurable disease as defined by RECIST 1.1 and adequate organ function. Results: Twenty-two patients were enrolled in 6 dose levels, 2 with daily dosing and 4 with twicedaily dosing ranging from 1 to 5 grams daily. All were evaluated for toxicity and 20 for response. No treatment-related dose-limiting toxicities (DLTs) were reported and the recommended phase II dose (RP2D) was determined to be 2.5 g twice daily. Seven adverse events in 5 patients were reported as possibly drug-related; 6 were GI toxicity and 1 was a skin disorder. All were grade 1 except one grade 2 vomiting. No RECIST responses were seen. Six pts were treated with > 2 cycles; one for 8 cycles. Four patients had reductions in TGF –β and EGF, exploratory biomarkers possibly suggestive of a drug effect. Plasma half-lives of 1 -2 hours were noted for all parent drug chemical markers with no accumulation over time. Conclusion: OMN54 was well tolerated, with no DLTs observed. Further studies at the RP2D will assess the biological activity.

scholarly journals Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions

2020 ◽  
Vol 16 (9) ◽  
pp. e859-e867
Author(s):  
Rachel S. Hianik ◽  
Gavin P. Campbell ◽  
Eli Abernethy ◽  
Colleen Lewis ◽  
Christina S. Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Phase I ◽  
Shared Decision Making ◽  
Phase I Trial ◽  
Performance Status ◽  
Shared Decision ◽  
Phase I Clinical Trials ◽  
Decision Making Model

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient’s opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2

2019 ◽  
Vol 37 (3) ◽  
pp. 230-238 ◽  
Author(s):  
Teresa Macarulla ◽  
Roberto Pazo-Cid ◽  
Carmen Guillén-Ponce ◽  
Rafael López ◽  
Ruth Vera ◽  
...  
Keyword(s):  
Phase I ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Ductal Adenocarcinoma ◽  
Tolerability Profile ◽  
Ecog Performance Status ◽  
Actuarial Survival ◽  
Number Of Patients

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

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