Phase I study of preoperative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3636-3636
Author(s):  
Gopi Kesaria Prithviraj ◽  
Kun Jiang ◽  
Xiuhua Zhao ◽  
Dung-Tsa Chen ◽  
Brian Morse ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
External Radiation ◽  
External Radiation Therapy

scholarly journals Phase I study of pre-operative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma

2016 ◽  
Vol 118 (2) ◽  
pp. 382-386 ◽  
Author(s):  
Richard Kim ◽  
Gopi Kesaria Prithviraj ◽  
Ravi Shridhar ◽  
Sarah E. Hoffe ◽  
Kun Jiang ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
External Radiation ◽  
External Radiation Therapy

Phase I study of preoperative capecitabine and lenvatinib with external radiation therapy in locally advanced rectal adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 694-694
Author(s):  
Jessica Frakes ◽  
Rutika Mehta ◽  
Sarah E. Hoffe ◽  
Iman Imanirad ◽  
Maria E Martinez Jimenez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
Radiation Therapy ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Vascular Endothelial Cell ◽  
Rectal Adenocarcinoma ◽  
External Beam Radiation ◽  
Beam Radiation

694 Background: Despite routine use of neoadjuvant chemoradiation, patients with advanced rectal tumors experience significant rates of treatment failure and recurrence. Radiation resistance is a particular problem. Dual targeting of PDGF and VEGFR (Vascular endothelial cell growth factor receptor) in combination with radiation can enhance tumor response. Lenvatinib inhibits the kinase activities of VEGFR1-3, FGFR1-4, PDGFRα, KIT, and RET and in vivo results show that it effectively delays the growth of human colorectal xenografts. Methods: This is a phase I clinical trial of lenvatinib in combination with capecitabine administered with radiation. Patients with stage II or III rectal cancer confirmed by endoscopic ultrasound or MRI were eligible for the study. In this 3+3 phase I study with 3 cohorts, patients were treated with escalating doses of lenvatinib administered in combination with standard doses of capecitabine (850 mg/m2 PO BID D1-5 weekly for 5 ½ to 6 weeks) and external beam radiation therapy (180 cGY on D1-5 weekly for 5 ½ to 6 weeks). Patients underwent surgery 6-10 weeks after neoadjuvant therapy. Results: Nine patients have been enrolled in the 3 cohorts with the median age of 51 years. Lenvatinib dosing started at 14 mg PO daily (cohort 1) and was safely escalated to 20 mg PO daily (cohort 2) followed by 24 mg PO daily (cohort 3). There were no DLTs at the maximum tested dose of lenvantinib (24 mg). 5 patients have undergone low anterior resection and 4 have had abdominoperineal resection. The pathological complete response (pCR) rate was 33.33%, and downstaging was observed in 100% of patients. Median neoadjuvant rectal cancer score (NAR) was 8.7. Three pts had grade 3 events (2 hypertension (HTN), 1 lymphopenia) without any grade 4 events. Most common AEs were HTN and fatigue. No perioperative complications were observed. Tissues for all pts have been collected for planned correlative studies. Conclusions: This study shows that the combination of lenvatinib with capecitabine, and EBRT is well tolerated. NAR score and downstaging rates are encouraging. Currently we are enrolling 10 additional pts at the maximum tested dose of lenvatinib to further evaluate efficacy and safety. Clinical trial information: NCT02935309.

A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
B. G. Czito ◽  
C. Willett ◽  
P. Kennedy-Newton ◽  
D. S. Tyler ◽  
H. Hurwitz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Study ◽  
Locally Advanced ◽  
Exploratory Laparotomy ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Level 1

281 Background: Localized PC is commonly managed with chemoradiotherapy, with or without surgical resection. The optimal combination of agents and doses is the subject of continued investigation. This phase I study examines the combination of two targeted radiosensitizing agents in combination with radiation therapy. Methods: Eligible patients had resectable, borderline resectable or locally advanced adenocarcinoma. Patients received RT (1.8 Gy qd to 50.4 Gy) concurrent with bevacizumab and erlotinib. Dose-level 1 was bevacizumab 10 mg/kg weeks 1, 3 and 5 and erlotinib 100 mg daily, RT days only. Drug doses were escalated depending on encountered toxicity. The primary endpoint was determination of the maximally tolerated dose of this combination. Secondary endpoints included toxicity and activity assessment. Results: Nine patients were enrolled in the phase I study. Maximal EUS/CT stage was T2N0 (n=1), T3N0 (n=1), T3N1 (n=2) or T4N0 (n=5). Of 3 patients in dose-level 1, two had radiographic stable disease (SD) and one partial response (PR). One pt underwent exploratory laparotomy and found to be unresectable, experiencing prolonged postoperative incisional healing. Three patients were then enrolled at dose-level 2 (bevacizumab 10 mg/kg, erlotinib 125 mg). Two had SD and one progressive disease (PD). One pt underwent exploratory laparotomy, aborted due to previously undetected hepatic metastases. Three patients were then enrolled at dose-level 3 (bevacizumab 10 mg/kg, erlotinib 150 mg). One pt had SD and two PR. One pt underwent distal pancreatectomy, experiencing postoperative pancreatic leak and abscess formation. All patients with elevated CA 19-9 at baseline had a decrease, with amedian decrease of 69% (R:13-93%). Dose-limiting toxicity (DLT) was not encountered at any dose-level. Primary non-dose limiting toxicities in all cohorts included NCI CTCAE v3.0 grade 1-2 nausea/vomiting, rash, diarrhea, fatigue, and anorexia. Conclusions: Concurrent chemoradiotherapy utilizing erlotinib and bevacizumab is reasonably well-tolerated. The recommended phase II dose is bevacizumab 10 mg/kg weeks 1, 3, and 5 and erlotinib 150 mg RT days only. Phase II accrual is underway. [Table: see text]

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