PHASE I STUDY OF BESTATIN: (II) CLINICAL TRIAL OF BESTATIN IN MALIGNANT SKIN TUMORS

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.

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End-of-life health care utilization (EOLHCU) in patients with thoracic, head and neck cancers with or without phase I study participation at a single institution.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19153 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19153-e19153

Author(s):

Dominic Min-Tran ◽

Annika Gustafson ◽

Keith D. Eaton ◽

Elizabeth Trice Loggers ◽

Cristina P. Rodriguez ◽

...

Keyword(s):

Health Care ◽

Clinical Trial ◽

Phase I ◽

Head And Neck ◽

End Of Life ◽

Phase I Study ◽

Care Utilization ◽

Study Participation ◽

Quality Of Death

e19153 Background: Several retrospective studies suggest patients enrolled in clinical trials have more end-of-life health care utilization (EOLHCU). This is particularly concerning for phase I clinical trial participants who are known to have therapeutic misconceptions about the purpose and benefits of phase I clinical trial participation. Methods: We identified all phase I participants at the Seattle Cancer Care Alliance (SCCA) with thoracic, head and neck cancers (THNC) who died between July 1, 2014 and June 30, 2018(P1C). We compared them to 139 randomly selected THNC patients who died within the same time period without phase I study participation (NP1C). Patient records were abstracted from the electronic health record (and Epic Care Everywhere if patients received EOL care outside of SCCA). A chi-square test was used to compare categorial variables and t-tests were used for numerical variables. Results: 67 P1C patients were identified; 3 patients had no outside records at the end of life and were removed from the database. No statistically significant differences in gender, ethnicity, marital status, or form of insurance were found between the two groups. P1C patients were younger (median age of 62 (interquartile range (IQR) 55-69) vs. 66 (IQR 59-72), p=0.008) and had more lines of therapy from diagnosis until death (median 4 (IQR 1-3) vs. 2 (IQR 1-3), p=<0.0001). No difference in end-of-life care or quality of death metrics were found between the two groups, however a trend toward more referrals to palliative care were noted in phase I participants. (Table). Conclusions: At our center no differences in EOLHCU or quality of death parameters were seen in THNC patients who did or did not participate in phase I studies. [Table: see text]

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