scholarly journals Phase I trial of a murine antibody to MUC1 in patients with metastatic cancer: evidence for the activation of humoral and cellular antitumor immunity

2004 ◽  
Vol 15 (12) ◽  
pp. 1825-1833 ◽  
Author(s):  
J.S. de Bono ◽  
S.Y. Rha ◽  
J. Stephenson ◽  
B.C. Schultes ◽  
P. Monroe ◽  
...  
Keyword(s):  
Phase I ◽  
Antitumor Immunity ◽  
Phase I Trial ◽  
Metastatic Cancer ◽  
Murine Antibody

A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer

2015 ◽  
Vol 33 (3) ◽  
pp. 710-719 ◽  
Author(s):  
Analia Azaro ◽  
Jordi Rodon ◽  
Antonio Calles ◽  
Irene Braña ◽  
Manuel Hidalgo ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Metastatic Cancer ◽  
Akt Inhibitor ◽  
S6 Kinase ◽  
P70 S6 Kinase

A novel phase I trial design featuring a two-dimensional dose-finding algorithm optimizing the dose of gemcitabine and doxorubicin with bortezomib in metastatic urothelial carcinoma (UC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 263-263 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Sijin Wen ◽  
Yu Shen ◽  
Kristi Stigall ◽  
David James McConkey ◽  
...  
Keyword(s):  
Phase I ◽  
Trial Design ◽  
Phase I Trial ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Fixed Ratio ◽  
Single Component ◽  
Neutropenic Fever ◽  
Dose Finding ◽  
Poor Renal Function

263 Background: Preclinical studies suggested that bortezomib (B) enhanced the activity of gemcitabine and doxorubicin (GA) in UC; thus we sought to define possible combinations of bortezomib with this doublet. We employed a novel phase I trial design systematically exploring doses in 2 dimensions. The method estimates an isotoxic curve allowing not only a combination with approximately equal (with respect to single component MTD) contributions of the two components to be found, but also combinations emphasizing one component or the other. Methods: Since 11/06, 74 patients with previously treated metastatic cancer were enrolled (70 UC, 3 prostate, 1 renal). GA was treated as a single component and given in a fixed ratio to a maximum of 900 and 50 mg/m2, and B to a maximal dose of 1.6 mg/m2 IV, with dosing every 14 days. After determining the MTD along the diagonal, we then decreased the dose of B, increasing GA, and vice versa, exploring doses along an isotoxic curve aiming for ≤ 30% dose limiting toxicity (DLT) in cycle 1. The objective response rate (ORR) includes PR or CR, and excludes SD. Results: The MTD along the diagonal for GAB was 756, 42, and 1.4 mg/m2, respectively. Doses maximizing the GA (900, 50) required reduction of B to 1.2 mg/m2. Likewise, doses maximizing B (1.6) required reduction of GA to 559 and 33 mg/m2. The most common DLT were thrombocytopenia 14%, neutropenic fever 5%, and mucositis 1%. There was minimal activity at the on-diagonal MTD with an ORR 1/10. Of the tolerable doses along the isotoxic curve, the greatest activity was seen when maximizing B (1.5-1.6 mg/m2, ORR 7/12 (58%)). The ORR when maximizing GA was 4/10. The most frequent ≥ G3 toxicities include: thrombocytopenia (26%), neutropenia (26%), anemia (24%), fatigue (8%), and neutropenic fever or infection (12%). Treatment was tolerable in poor renal function; 36 patients (49%) had a GFR < 50 ml/min. Conclusions: The combination of GAB has promising activity at doses maximizing proteosome inhibition, despite relatively low doses of GA. Traditional phase I design dosing to the MTD "along the diagonal" would have lead to the incorrect conclusion that there was minimal activity. Clinical trial information: NCT00479128.

A Phase I trial of the sulfonylhydrazine alkylator, VNP40101M (101M), administered weekly in patients (pts) with metastatic cancer

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 2060-2060 ◽  
Author(s):  
J. Murren ◽  
S. Gerson ◽  
S. Kummar ◽  
M. Davies ◽  
S. Remick ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Metastatic Cancer

scholarly journals Phase I trial of afatinib and 3-weekly trastuzumab with optimal anti-diarrheal management in patients with HER2-positive metastatic cancer

2018 ◽  
Vol 82 (6) ◽  
pp. 979-986 ◽  
Author(s):  
Nicolas Martin ◽  
Nicolas Isambert ◽  
Carlos Gomez-Roca ◽  
Rainer-Georg Goeldner ◽  
Sylvie Zanetta ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Metastatic Cancer ◽  
Her2 Positive

Phase I trial of pemetrexed plus oxaliplatin administered every other week in patients with metastatic cancer

2008 ◽  
Vol 26 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Daniel G. Stover ◽  
A. Craig Lockhart ◽  
Jordan D. Berlin ◽  
Emily Chan ◽  
Alan B. Sandler ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Metastatic Cancer

Fixed dose rate (FDR) gemcitabine (G) and capecitabine (C) in patients with advanced and/or metastatic cancer: phase I trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12016-12016
Author(s):  
D. Santini ◽  
B. Vincenzi ◽  
V. Virzì ◽  
A. La Cesa ◽  
G. Schiavon ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Rate ◽  
Cancer Patients ◽  
Dose Level ◽  
Phase I Trial ◽  
Metastatic Cancer ◽  
Fixed Dose ◽  
Clinical Activity ◽  
Open Label ◽  
Fixed Dose Rate

12016 Background: Combination of C and G has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. To determine the toxicity of C plus Fixed Dose Rate (FDR) G in metastatic cancer patients, a phase I trial was conducted. Methods: This is an open-label, single-center, dose-escalating phase I study. C was administered orally according to the standard 21-day schedule: bid in equal doses (650 mg/m2 bid) for 14 days every 21 days. G was administered at a FDR of 10 mg/m2 per min in escalating durations of infusion on days 1 and 8 every 21 days. The doses of G explored were 600, 700, 800 mg/m2 infused at FDR in 60, 70 and 80 minutes, respectively. 15 pts (10 female, 5 male), aged 37–70 yr (median 66) with a variety of advanced solid tumors have been treated (11 peri-ampullary cancers, 3 colorectal cancers and 1 ovarian cancer). The FDR G dose was escalated when 3 patients in a cohort had completed two cycles of treatment without experiencing dose-limiting toxicities (DLT). The MTD was defined as the dose level at which no more than one of nine patients experienced a DLT. Results: No DLT occurred at doses of 600 and 700 mg/m2 in any of the 3 patients included at each level. At 800 mg/m2, 1 of 9 patients experienced DLT (neutropenia grade 4 with fever). The non-haematological toxicities have been generally mild or moderate in all patients (grade 2 stomatitis: 4 patients; grade 2 fatigue: 3 patients; grade 2 nausea/vomiting: 2 patients). 2 patients showed one episode of grade 4 neutropenia spontaneously regressed in 3 days. 2 patients showed one episode of grade 2 thrombocytopenia. The recommended dose for further studies is C bid in equal doses (650 mg/m2 bid) for 14 days (28 doses) plus FDR G at 800 mg/m2 infused in 80 minutes on days 1 and 8 every 21 days. Other patients with periampullary carcinoma are being evaluated at the same dose level, with an ongoing evaluation of cumulative (all cycles) toxicity and efficacy. In terms of response, we have observed 2 PR and 3 SD in the 6 pancreatic cancer patients evaluated for response after the first 3 cycles. Conclusions: C plus FDR G combination seems to be a feasible and safety approach which has demonstrated promising clinical activity. No significant financial relationships to disclose.

A novel phase I trial design featuring a two-dimensional dose-finding algorithm optimizing the dose of gemcitabine and doxorubicin with bortezomib in metastatic urothelial carcinoma (UC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4548-4548
Author(s):  
Arlene O. Siefker-Radtke ◽  
Sijin Wen ◽  
Yu Shen ◽  
Kristi Stigall ◽  
David James McConkey ◽  
...  
Keyword(s):  
Phase I ◽  
Trial Design ◽  
Phase I Trial ◽  
Metastatic Cancer ◽  
Phase 1 ◽  
Objective Response ◽  
Fixed Ratio ◽  
Single Component ◽  
Neutropenic Fever ◽  
Dose Finding

4548 Background: Preclinical studies suggested that bortezomib (B) enhanced the activity of gemcitabine and doxorubicin (GA) in UC; thus we sought to define possible combinations of bortezomib with this doublet. We employed a novel phase I trial design systematically exploring doses in 2 dimensions. The method estimates an isotoxic curve allowing not only a combination with approximately equal (with respect to single component MTD) contributions of the two components to be found, but also combinations emphasizing one component or the other. Methods: Since 11/06, 74 patients with previously treated metastatic cancer were enrolled (70 UC, 3 prostate, 1 renal). GA was treated as a single component and given in a fixed ratio to a maximum of 900 and 50 mg/m2, and B to a maximal dose of 1.6 mg/m2 IV, with dosing every 14 days. After determining the MTD along the diagonal, we then decreased the dose of B, increasing GA, and vice versa, exploring doses along an isotoxic curve aiming for ≤ 30% dose limiting toxicity (DLT) in cycle 1. The objective response rate (ORR) includes PR or CR, and excludes SD. Results: The MTD along the diagonal for GAB was 756, 42, and 1.4 mg/m2, respectively. Doses maximizing the GA (900, 50) required reduction of B to 1.2 mg/m2. Likewise, doses maximizing B (1.6) required reduction of GA to 559 and 33 mg/m2. The most common DLT were thrombocytopenia 14%, neutropenic fever 5%, and mucositis 1%. There was minimal activity at the on-diagonal MTD with an ORR 1/10. Of the tolerable doses along the isotoxic curve, the greatest activity was seen when maximizing B (1.5-1.6 mg/m2, ORR 7/12 (58%)). The ORR when maximizing GA was 4/10. The most frequent ≥ G3 toxicities include: thrombocytopenia (26%), neutropenia (26%), anemia (24%), fatigue (8%), and neutropenic fever or infection (12%). Treatment was tolerable in poor renal function; 36 patients (49%) had a GFR < 50 ml/min. Conclusions: The combination of GAB has promising activity at doses maximizing proteosome inhibition, despite relatively low doses of GA. Traditional phase 1 design dosing to the MTD "along the diagonal" would have lead to the incorrect conclusion that there was minimal activity. Clinical trial information: NCT00479128.

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