Safety and activity of Combined AVElumab with Axitinib in unresectable or metastatic Thymomas B3 and Thymic carcinomas: The CAVEATT study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21114-e21114 ◽  
Author(s):  
Fabio Conforti ◽  
Laura Pala ◽  
Chiara Catania ◽  
Paolo Andrea Zucali ◽  
Paolo Della Vigna ◽  
...  
Keyword(s):  
Treatment Options ◽  
Predictive Biomarkers ◽  
Primary Objective ◽  
Preliminary Results ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Hand Foot Syndrome ◽  
Eortc Qlq C30 ◽  
Antiangiogenic Drugs ◽  
Eortc Qlq

e21114 Background: Patients (pts) with advanced B3 thymoma (B3T) and thymic carcinoma (TC) resistant to chemotherapy have limited treatment options. Treatment with Anti-PD1 showed not negligible toxicity and limited activity, and anti-VEGFR drugs obtained limited and short lasting antitumor responses. No data on combined anti-PD1/PD-L1 with antiangiogenic drugs are available in B3T/TC. We report preliminary results on safety and activity of avelumab combined with axitinib in this pts population. Methods: The CAVEATT is a single arm, multicentric, phase II trial in immunotherapy-naive pts with advanced B3T or TC, progressing after at least one line of platinum based chemotherapy. Prior therapy with antiangiogenic drugs is allowed. Pts received Avelumab 10 mg/kg iv every 2 weeks and Axitinib 5 mg twice a day until progression or toxicity. The primary objective of the study is overall response rate (ORR) by RECIST 1.1; secondary endpoints include ORR by irRC and ITMIG, and QoL by EORTC QLQ-C30. An interim futility analysis is planned after the enrollment of the first 18 patients. If at least 5 out of 18 patients will obtain a PR, the accrual will continue to reach the total number of 33 pts, according with a Simon’s minimax design. Tumor and blood samples are collected at baseline and whenever feasible at disease progression, to identify predictive biomarkers of response and mechanisms of resistance to treatment. Results: 1 pt with B3T and 12 with TC were enrolled from April 2019 to January 2020. Median age was 59 years (range 33-77). 8 pts received ≥2 previous line of therapies, and 6 pts were pretreated with an antiangiogenic drug. The median follow-up was 5.1 months. 10 pts were evaluable for response. The proportions of patients who achieved a partial response (PR) or a stable disease (SD) were respectively 40% (95% CI 17%–69%) and 60% (95% CI 30%–83%). The median PFS was 7.9 months (95% CI 2.5–NA) 12 pts were evaluable for toxicity. Treatment-related adverse events (AE) of grade 1 or 2 occurred in 7 (58%) pts, and the most common was diarrhea (3 pts). Grade ≥3 AEs occurred in 2 (17%) pts: 1 had G3 hyperthension and 1 G3 hand foot syndrome, both leading to axitinib drug reduction. No immune-related AEs (irAEs) were observed. No patient stopped treatment for toxicity, 5 pts stopped for progressive disease, and 8 pts are still on treatment. Conclusions: Preliminary results suggest promising antitumor activity and a good toxicity profile of the combination of axitinib and avelumab in pts with advanced B3T and TC. Accrual is ongoing to reach the target of 33 pts Clinical trial information: 2017-004048-38 .

Sequential compared to combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (ACC): A Dutch Colorectal Cancer Group (DCCG) phase III study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
C. J. Punt ◽  
M. Koopman ◽  
J. Douma ◽  
J. Wals ◽  
A. H. Honkoop ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Treatment Strategies ◽  
Sequential Therapy ◽  
Phase Iii ◽  
Cancer Group ◽  
Neutropenic Sepsis ◽  
Hand Foot Syndrome ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

4012 Background: Overall survival (OS) in phase III studies with 1st line combination therapy in ACC may be influenced by imbalances in salvage treatments. This is the first study that prospectively investigates the sequential vs the combined use of all available effective cytotoxic drugs. Methods: Previously untreated patients (pts), WHO PS 0–2 were randomized between 1st line capecitabine (Cap), 2nd line irinotecan (Iri), and 3rd line Cap + oxaliplatin (CapOx) (Arm A, sequential) vs 1st line CapIri and 2nd line CapOx (Arm B, combination). The dose of Cap was 1250 mg/m2 (mono) or 1,000 mg/m2 (combination) b.i.d. day 1–14, Iri 350 mg/m2 (mono) or 250 mg/m2 (combination), and Ox 130 mg/m2. All cycles were q 3 weeks with Iri/Ox given i.v. on day 1. Response was assessed q 3 cycles. Primary endpoint was OS. The study was designed to detect a 20% reduction in the hazard of death (HR=0.80) for an increase in median OS from 14 to 17.5 months (a=0.05, 2-tailed test). Results: 820 pts were randomized between Jan ‘03 and Dec ‘04 in 74 Dutch hospitals. Of 804 eligible pts, 796 received = 1 cycle. Median age was 63 (27–84) yrs, median WHO PS 0 (0–2), median follow-up 32 months. Pts (n) in arm A: 398 (1st line), 248 (2nd line), 141 (3rd line); arm B: 398 (1st line), 210 (2nd line). Median OS in arm A was 16.3 months (95%CI 14.3–18.2) and in arm B 17.7 months (95%CI 15.2–19.4), logrank p=0.2. Overall gr 3–4 toxicity over all lines did not differ significantly except for gr 3 hand-foot syndrome (HFS) (13% in A and 6% in B, p=0.0009). Death was probably related to treatment in 11 pts (neutropenic sepsis and/or diarrhea, 8 arm A, 3 arm B) and involved protocol violations in some. In 1st line significant differences in gr 3–4 toxicity in arm A vs arm B were diarrhea (10% vs 25%, p<0.0001), febrile neutropenia (1% vs 6%, p=0.0001) and HFS (12% vs 5%, p=0.0004). All-cause 60-day mortality was 3.0% (n=12) in arm A and 4.5% (n=18) in arm B. Updated results will be presented at the meeting, including data on QoL (EORTC QLQ C30). Conclusions: Combination therapy does not significantly improve OS compared with sequential therapy. Both treatment strategies are valid options for pts with ACC. No significant financial relationships to disclose.

Assessing financial difficulty in patients with multiple myeloma: Preliminary results of ALLIANCE A231602CD.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8031-8031
Author(s):  
Rena M. Conti ◽  
Shaylene McCue ◽  
Travis Dockter ◽  
Bruce D. Rapkin ◽  
Stacie Dusetzina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Primary Objective ◽  
National Study ◽  
Financial Difficulty ◽  
The Past ◽  
Financial Difficulties ◽  
Study Results ◽  
Eortc Qlq C30 ◽  
Chart Abstraction ◽  
Eortc Qlq

8031 Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices.Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months.Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.

scholarly journals Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer

2020 ◽  
Author(s):  
Zhen Yuan ◽  
Ying Zhang ◽  
Dongyan Cao ◽  
Keng Shen ◽  
Qingshui Li ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Low Frequency ◽  
Pegylated Liposomal Doxorubicin ◽  
Primary Objective ◽  
Open Label ◽  
Previous Response ◽  
Peritoneal Cancer ◽  
Platinum Based Chemotherapy ◽  
Hand Foot Syndrome ◽  
The Impact

Abstract Objective: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4%-46.4%), and the DCR was 65.2% (95% CI, 56.4%-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Interim results of a multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 358-358 ◽  
Author(s):  
Jill Lacy ◽  
Fabienne Portales ◽  
Pascal Hammel ◽  
Roberto A. Pazo Cid ◽  
Jose Luis Manzano Mozo ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Options ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Treatment Phase ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Eortc Qlq C30 ◽  
Treatment Naïve ◽  
Eortc Qlq

358 Background: Treatment options for pts with LAPC are limited and generally similar to those for metastatic PC (mPC). The phase 3 MPACT trial of pts with mPC demonstrated a > 3-fold shrinkage of primary tumors with nab-P + G vs G, suggesting the potential of nab-P + G for LAPC treatment. Here, we present interim results on disease control rate (DCR), adverse events (AEs), and quality of life (QoL) from the international phase 2 LAPACT trial. Methods: Pts with treatment-naive unresectable LAPC and ECOG performance status of 0 or 1 received 6 cycles (C) of nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 of each 28-day C. After the initial nab-P + G treatment phase, pts without PD and unacceptable AEs were eligible for investigator’s choice (IC) of continued treatment with nab-P + G, chemoradiation, or surgery. Surgery could occur prior to completing 6 C in the case of a major response. Pt-reported QoL was assessed via EORTC QLQ-C30 and QLQ-PAN26 questionnaires at screening and prior to infusion on day 1 of each C. Results: As of Aug 17, 2016, 47 pts completed (28/47, 60%) or discontinued (19/47, 40%) the initial nab-P + G treatment (median, 5 C). Median age was 66 years (range, 44 - 86). The most frequent reasons for discontinuation were AE (10/47 [21%], with the most common being neutropenia and abnormal liver function [2 pts each]) and PD (3/47, 6%). The most common grade ≥ 3 AEs were neutropenia (34%) and anemia (11%). The DCR ≥ 16 weeks was 76% (34/45 efficacy-evaluable pts [defined as having evaluable baseline and ≥ 1 postbaseline scan]; PR, n = 13; SD, n = 21). Twenty-two pts (47%) were assigned by the investigators to an IC treatment: 4 (9%) to continue nab-P + G, 8 (17%) to chemoradiation, and 10 (21%) to surgical resection. Mean QoL scores remained stable during the study, with improved symptom scores for appetite and pain. During the initial nab-P + G treatment phase, most patients reported a complete resolution of certain limitations, including depression (≈ 80%), constipation (≈ 62%), and nausea (≈ 93%). Conclusions: These interim results suggest that for pts with LAPC, nab-P + G is tolerable and produces a promising DCR. On average, QoL scores remained stable during nab-P + G treatments. Clinical trial information: NCT02301143.

scholarly journals Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e001126
Author(s):  
Claire F Friedman ◽  
Alexandra Snyder Charen ◽  
Qin Zhou ◽  
Michael A Carducci ◽  
Alexandre Buckley De Meritens ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Primary Objective ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Recurrent Cervical Cancer ◽  
Platinum Based Chemotherapy

BackgroundThere are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.MethodsWe report the results from a phase II, open-label, multicenter study (NCT02921269). Patients with advanced cervical cancer were treated with bevacizumab 15 mg/kg intravenous every 3 weeks and atezolizumab 1200 mg intravenous every 3 weeks. The primary objective was to measure the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsIn the total evaluable population (n=10), zero patients achieved an objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1, resulting in a confirmed ORR of 0%. Of note, there were two patients who achieved an unconfirmed PR. The DCR by RECIST V.1.1 was 60% (0% complete response, 0% partial response, 60% stable disease). Median PFS was 2.9 months (95% CI, 1.8 to 6) and median OS was 8.9 months (95% CI, 3.4 to 21.9). Safety results were generally consistent with the known safety profile of both drugs, notably with two high-grade neurologic events.ConclusionsThe combination of bevacizumab and atezolizumab did not meet the predefined efficacy endpoint, as addition of bevacizumab to PD-L1 blockade did not appear to enhance the ORR in cervical cancer.

scholarly journals Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhen Yuan ◽  
Ying Zhang ◽  
Dongyan Cao ◽  
Keng Shen ◽  
Qingshui Li ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Low Frequency ◽  
Pegylated Liposomal Doxorubicin ◽  
Primary Objective ◽  
Open Label ◽  
Previous Response ◽  
Peritoneal Cancer ◽  
Platinum Based Chemotherapy ◽  
Hand Foot Syndrome ◽  
The Impact

Abstract Objective To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

A pilot study exploring issues around decision making in older women with primary operable breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20588-e20588
Author(s):  
Ruth M. Parks ◽  
Louise Hall ◽  
Siau-Wei Tang ◽  
Radhika Lakshmanan ◽  
Penny Howard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Pilot Study ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Negative Feeling ◽  
Structured Interviews ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
The Right

e20588 Background: Decision making process related to cancer treatment is complex, influenced by tumour factors, patients and clinicians, and may affect outcomes eg quality of life (QOL). Studies are scarce in exploring this subject in the older population. This pilot study aimed to investigate this in older (≥70 years) women newly diagnosed with clinically T0-2N0-1M0 breast cancer. Methods: Patients as described were invited to participate. Actual treatment planning was made by the clinical team and was not part of the study. Semi-structured interviews were conducted within 6 weeks and at 6 months, alongside Comprehensive Geriatric Assessment (CGA) and QOL assessment using EORTC QLQ-C30. Interview recordings were transcribed (intelligent verbatim) and then analysed by (i) identifying themes; and (ii) comparing them with CGA and QOL measures. Results: Forty-one patients took part at the time of analysis. The following themes emerged in different patient combinations, at both time points. 1) Symptoms - The majority presented symptomatically (87%, 21/31). At 6 months, 45% (18/40) reported a negative feeling, but 81% (22/27) said they would choose the same treatment again. 2) Knowledge - Most patients (80%, 28/35) knew someone with a cancer diagnosis, but did not know much about breast cancer or treatment (87%, 18/24). 3) Reactions - At diagnosis, only 48% (10/23) felt ‘shocked’ or ‘surprised,’ while the remainder had ‘no reaction’ or ‘were prepared’. The majority (91%, 29/32) felt that they had received enough information about treatment options or that they did not have an option. 4) QOL - Most patients (88%, 15/17) thought they had made the right treatment choice. The majority (86%, 6/7) were not worried about the future and 91% (10/11) reported no change in QOL. No relationship was seen between these interview findings and the treatment modalities received. These findings were consistent with the results of CGA and QOL assessment. Conclusions: These preliminary findings suggest that these patients were generally happy with the decision made for their treatments and had a fairly good QOL and future outlook. The study has now entered into a second stage where more in-depth interviews are being conducted.

Patient-reported outcomes and quality of life in ALTA: The randomized phase 2 study of brigatinib (BRG) in advanced ALK+ non–small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9066-9066
Author(s):  
Corey J. Langer ◽  
Hui Huang ◽  
Joice Huang ◽  
David Kerstein ◽  
William Reichmann ◽  
...  
Keyword(s):  
International Study ◽  
Cumulative Distribution ◽  
Phase 2 ◽  
Open Label ◽  
Meaningful Improvement ◽  
Prior Therapy ◽  
Anaplastic Lymphoma ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

9066 Background: The ALTA trial (NCT02094573), an open-label, phase 2, randomized, multicenter, international study, evaluated the efficacy and safety of BRG (arm A: 90 mg qd and arm B: 180 mg qd with 7-day lead-in at 90 mg) in patients (pts) with advanced anaplastic lymphoma kinase–positive (ALK+) NSCLC whose disease had progressed on prior therapy with crizotinib (CRZ). The objective of this analysis was to describe pt-reported outcomes (PROs) in the ALTA study. Methods: PROs were collected using the EORTC QLQ-C30 at baseline and on the first day of each cycle. Multivariable mixed effects models were constructed to estimate adjusted mean changes from baseline in QLQ-C30 scores. Cumulative distribution function (CDF) plots of EORTC QLQ-C30 change scores from baseline to Cycle 5 were generated to evaluate a clinically meaningful threshold of individual pt change, which was determined through anchor- and distribution-based methods. Results: Among 222 randomized pts, 208 (94%) completed the questionnaire at baseline and at least 1 on-treatment PRO follow-up. In multivariable analyses, there were no statistically significant differences in Global Health Status (GHS)/QOL between arms over time when adjusted for baseline score, ECOG status, and presence of liver or bone metastases. At Cycle 5, CDF plots indicated that 80% of all pts experienced an increase or no change in GHS/QOL scores; 50% of all pts experienced a clinically meaningful improvement. At Cycle 5, 80% of all pts reported a reduction or no change in pain score, and 90% of all pts reported a reduction or no change in dyspnea score. Approximately 30% of pts had clinically meaningful reductions in these symptoms. Less than 15% and < 5% of all pts reported clinically meaningful worsening of nausea/vomiting and diarrhea scores, respectively, at Cycle 5. Conclusions: Treatment with BRG for CRZ-refractory ALK+ NSCLC resulted in improved GHS/QOL scores and reduction in pain and dyspnea scores, while rates for nausea/vomiting and diarrhea were minimally worse. These pt-level benefits support BRG as a promising treatment option. Clinical trial information: NCT02094573.

scholarly journals Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer

2020 ◽  
Author(s):  
Zhen Yuan ◽  
Ying Zhang ◽  
Dongyan Cao ◽  
Keng Shen ◽  
Qingshui Li ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Low Frequency ◽  
Pegylated Liposomal Doxorubicin ◽  
Primary Objective ◽  
Open Label ◽  
Previous Response ◽  
Peritoneal Cancer ◽  
Platinum Based Chemotherapy ◽  
Hand Foot Syndrome ◽  
The Impact

Abstract Objective: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy.Methods: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints.Results: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4%-46.4%), and the DCR was 65.2% (95% CI, 56.4%-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires.Conclusions: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Preliminary results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8009-8009 ◽  
Author(s):  
R. K. Amaravadi ◽  
L. M. Schuchter ◽  
A. Kramer ◽  
S. F. Barth ◽  
J. Villanueva ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Prior Therapy ◽  
Optimal Dosing ◽  
Hand Foot Syndrome ◽  
Correlative Studies ◽  
Grade 3 ◽  
Ecog Ps

8009 Background: Sorafenib (SO) is an oral Raf kinase/VEGFR-2 inhibitor that has anti-melanoma activity when given with carboplatin/paclitaxel. The primary objective of this study is to estimate the duration of progression-free survival (PFS) for patients with metastatic melanoma (MM) taking SO + temozolomide (TEM). Secondary objectives are to determine the optimal dosing of TEM when given with SO, response, and toxicity rates. Correlative studies include BRAF genotyping and assessment of intratumoral Raf inhibition. Methods: Patients with MM and ECOG PS<2 are eligible. Prior therapy is allowed. Accrual is designed for 167 patients in one stage. All patients receive SO 400 mg po bid continuously. After one week of SO alone, patients without brain metastasis and no prior TEM are randomized to receive either extended daily dosing (EDD): TEM 75 mg/m2 po qd for 6 /8 weeks (Arm A), or standard dosing (STD): TEM 150 mg/m2 po qd for days1–5/28 (Arm B). Patients with prior TEM use are treated with EDD (Arm C) and patients with brain metastasis without prior TEM are treated with STD (Arm D). Responses are assessed using RECIST criteria. Results: 65 patients were evaluated for toxicity. Of these, 58 received SO + TEM and were evaluable for response (Table). SO + TEM resulted in a 24% overall response rate (ORR) [95% CI 11–41%] in patients without brain metastasis or prior TEM and 20% ORR [95% CI 3–56%] in patients with brain metastasis and no prior TEM. Observed grade 3 toxicities attributable to study medication were: hand-foot syndrome (12%), rash (8%), nausea (5%), anorexia (8%), and hypertension (3%). Nausea and anorexia were more prevalent with STD. Tumor blocks and 8 paired biopsy samples have been collected for correlative studies. Conclusions: Initial phase II results demonstrate encouraging antitumor activity and safety profile for SO + TEM in MM. Updated PFS data, response and toxicity rates, and correlative results will be presented. [Table: see text] [Table: see text]

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