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]

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 docetaxel as a radiosensitizer for locally advanced squamous cell cervical cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5053-5053
Author(s):  
E. A. Alvarez ◽  
A. H. Wolfson ◽  
J. M. Pearson ◽  
M. Crisp ◽  
N. C. Lambrou ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Study ◽  
Locally Advanced ◽  
Concurrent Radiotherapy ◽  
Level 1 ◽  
Experienced Grade

5053 Background: Concomitant radiotherapy with cisplatin chemotherapy is the standard of care for locally advanced squamous cell cervical cancer (LASCCC). Alternatives to cisplatin are needed due to patient intolerance or toxicity. Taxanes have demonstrated clinical cytotoxic activity to SCCC and in-vitro radio-sensitization. This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy for the primary treatment of LASCCC. Methods: Twenty-three patients with FIGO stage IIB-IVA LASCCC without para-aortic lymph node involvement were screened and 13 enrolled in a dose-escalating phase I study. Docetaxel dose levels were 20 mg/m2, 30 mg/m2 and 40 mg/m2 given intravenously every 7 days for 6 cycles. Three patients were treated at each dose level and six patients received the MTD. Radiation therapy (RT) delivered a total dose of approximately 85 Gy to Point “A”. RT was administered with megavoltage external beam irradiation (EBI) at 1.8 Gy/fraction (fx) for 30 fxs to the pelvis over 6 weeks using a 4-field “box” technique for the first 25 fxs. A midline shield was applied for the last 5 fxs. Following EBI, patients underwent low-dose-rate brachytherapy. Results: Thirteen patients completed 4 - 6 cycles of chemotherapy. The other patients withdrew consent or needed alternative treatment before initiating the study. Reasons for completing less than 6 cycles were: noncompliance (5), adverse event (2), progression (1). One patient was lost to follow-up after 4 cycles. DLT’s were not observed at the 20 mg/m2 dose level. At the 30 mg/m2 dose level, 1/4 patient had a treatment-unrelated pelvic abscess and celiotomy. Another had progression 4 months after treatment. At the 40 mg/m2 dose level, 1/6 patients had progression and experienced grade 2 pneumonia, not treatment related. DLT was not observed in 6 patients at the 40 mg/m2 level. Overall, 5/13 (38%) experienced grade 2 diarrhea, 5 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. Seven of 9 patients (78%) had no evidence of disease with follow-up ranging from 10–21 months. Conclusions: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for LASCCC is 40 mg/m2. The phase II trial is underway. No significant financial relationships to disclose.

A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14044-14044
Author(s):  
C. R. Kelsey ◽  
B. G. Czito ◽  
J. C. Bendell ◽  
C. G. Willett ◽  
M. A. Morse ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Infusion Pump ◽  
Symptom Control ◽  
Local Therapy ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Level 1 ◽  
Grade 3

14044 Background: Chemoradiotherapy is used to treat esophageal cancer with curative intent or local symptom control. A phase I study of 5-FU + CARB + TAX + EBRT showed 100% RR and 50% pCR rate. CAP allows for fluoropyrimidine treatment without the inconvenience of an infusion pump. CARB allows for platinum treatment with less toxicity than cisplatin. We evaluated this combination of agents in a phase I study. Methods: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus requiring local therapy received CAP (825 mg/m2 bid on radiation days) + CARB (AUC 2 qweek) + TAX (60 mg/m2 qweek) + EBRT (1.8 Gy qd to 50.4 Gy). DLT was defined as any grade 4 heme toxicity, grade 3 heme toxicity lasting ≥ 7 days, ≥ grade 3 N/V, diarrhea, or esophagitis lasting ≥ 4 days despite optimal medical management, grade 3 other toxicity, inability to deliver 75% of scheduled CAP dose, or treatment delay > 3 days. Results: 13 pts were enrolled (10M, 3F). Median age was 62 (R- 48–78). EUS stage was uT3N0 (n=1), uT2N1 (n=1), or T3N1 (n=11). 2/3 pts had DLT at dose level 1 (both grade 4 esophagitis). Esophagectomy was performed in 2/3 patients, both pCR. Three pts were then enrolled at dose level -1 (CAP 600 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2). One patient developed DLT (grade 3 esophagitis) so 7 more pts were added at this dose level. Overall, 3/10 patients at dose level -1 developed DLT (two grade 3 esophagitis, one grade 3 hypotension). Esophagectomy was performed in 6/10 pts - 2/6 had pCR; 6/6 had pathologic downstaging. Conclusions: MTD for this regimen was CAP 625 mg/m2 bid + CARB AUC 1.5 + TAX 45 mg/m2 with EBRT to 50.4 Gy. However, at the MTD, this regimen is relatively toxic with no significant improvement in rate of pCR. [Table: see text]

A phase I study of tirapazamine in combination with radiation and weekly cisplatin in patients with locally advanced cervical cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5543-5543
Author(s):  
D. Rischin ◽  
K. Narayan ◽  
A. Oza ◽  
L. Mileshkin ◽  
D. Bernshaw ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Pulmonary Embolism ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Level 1 ◽  
Grade 3

5543 Background and Purpose: Hypoxia is an adverse prognostic factor in locoregionally advanced cervical cancer treated with radiation. GOG are currently studying the hypoxic cytotoxin, tirapazamine (TPZ) in combination with biweekly intermediate dose cisplatin (CIS) and radiation in a large phase III trial. The aim of this phase I study was to develop a better tolerated regimen that added TPZ to the standard regimen of radiation and weekly low dose CIS. Methods: Eligible patients had previously untreated carcinoma of the cervix, Stages IB2 - IVA. The starting schedule was radiotherapy (45 to 50.4 Gy external beam radiation followed by brachytherapy), with concomitant weekly CIS 40 mg/m2 weeks 1–6 and weekly TPZ 290 mg/m2 (prior to CIS) in weeks 1–5. Results: Between 3/05 and 7/06 eleven patients were enrolled, median age (range) 52 (31–65), squamous cell carcinoma 10, adenocarcinoma 1, 1B2–5, IIA-1, IIB-3, IIIB- 1, IVA-1. The first 2 patients on dose level 1 experienced a dose limiting toxicity (DLT), one grade 3 ALT (SGPT) elevation and grade 4 pulmonary embolism and one grade 3 ototoxicity. Doses were decreased to dose level -1 CIS 30 mg/m2 and TPZ 260 mg/m2. Three patients were treated without any DLTs. Six patients were then treated on dose level -1a, CIS 35 mg/m2 and TPZ 260 mg/m2, with 2 DLTs: grade 3 neutropenia with dose omission and grade 4 pulmonary embolism with major hemodynamic compromise. The sixth patient on dose level -1a withdrew from the trial in week 2 after being advised about the DLTs observed on this dose level. 3 additional patients will be accrued on dose level -1 to confirm safety of this dose level. One patient has relapsed in pelvic nodes, all other patients remain disease-free with a median followup of 10 months (range 5 - 21) Conclusions: The combination of weekly TPZ and CIS with radiation for locally advanced cervical cancer was associated with more toxicity than anticipated with the recommended dose level being TPZ 260 mg/m2, CIS 30 mg/m2. No significant financial relationships to disclose.

scholarly journals S0356: A Phase II Clinical and Prospective Molecular Trial With Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy Before Surgery for Patients With Esophageal Adenocarcinoma

2011 ◽  
Vol 29 (34) ◽  
pp. 4555-4560 ◽  
Author(s):  
Lawrence P. Leichman ◽  
Bryan H. Goldman ◽  
Pierre O. Bohanes ◽  
Heinz J. Lenz ◽  
Charles R. Thomas ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Neoadjuvant Therapy ◽  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
External Beam Radiation Therapy ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation

Purpose Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival. Patients and Methods Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m2 on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m2/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed for mRNA expression and polymorphisms in genes involved in drug metabolism and DNA repair. Results Ninety-three patients were evaluable. Two deaths (2.2%) were attributable to preoperative therapy, and two deaths (2.2%) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3% and 19.4% of patients, respectively. Seventy-nine patients (84.9%) underwent surgery; 67.7% of patients had R0 resections. Twenty-six patients (28.0%) had confirmed pCR (95% CI, 19.1% to 38.2%). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1%, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS. Conclusion Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.

Sign in / Sign up

Export Citation Format

Share Document