Rectal Adenocarcinoma Clinical Trial
Official title:
A Phase I Study of Talimogene Laherparepvec (Talimogene Laherparepvec) With Neoadjuvant Chemotherapy and Radiation in Adenocarcinoma of the Rectum
This phase I trial studies the best dose and side effects of talimogene laherparepvec in combination with 5-fluorouracil, leucovorin, oxaliplatin, capecitabine, and chemoradiation before surgery in treating patients with rectal cancer that has spread from where it started to nearby tissue and lymph nodes. Drugs used in immunotherapy, such as talimogene laherparepvec, may stimulate the body's immune system to fight tumor cells. Drugs used in chemotherapy, such as 5-fluorouracil, leucovorin, oxaliplatin, and capecitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving talimogene laherparepvec, 5-fluorouracil, leucovorin, oxaliplatin, and capecitabine and chemoradiation before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PRIMARY OBJECTIVE: I. To determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of talimogene laherparepvec in combination with chemotherapy and radiation in rectal cancer. SECONDARY OBJECTIVES: I. To establish safety and feasibility of the combination. II. To determine the neoadjuvant rectal (NAR) score of talimogene laherparepvec with chemotherapy and radiation. EXPLORATORY OBJECTIVES: I. To correlate genomic information including RAS, RAF mutation status with response, disease free survival (DFS) and/or overall survival (OS). II. To determine immunomodulatory changes following talimogene laherparepvec, chemotherapy and radiation treatment including proportions of immune cell infiltrates in serially collected peripheral blood and/or frozen tumor samples (pre-, on treatment, and at post progression). III. To identify magnetic resonance imaging (MRI)-based features including MRI circumferential margin (mrCRM) at baseline or post-therapy mrCRM, MRI tumor regression grade (mrTRG) to define determinants of response, DFS and OS. IV. To determine the disease free survival (DFS) and overall survival (OS) of talimogene laherparepvec with chemotherapy and radiation in patients undergoing curative resection. V. To determine the pathological complete response (pCR) rate of talimogene laherparepvec with chemotherapy and radiation. OUTLINE: This is a dose-escalation study of talimogene laherparepvec. Patients receive talimogene laherparepvec intralesionally via endoscopy on weeks 1, 4, 6, and 8. Patients receive 5-fluorouracil intravenously (IV) by bolus and over 46 hours, leucovorin IV bolus, and oxaliplatin IV over 2 hours on weeks 2 and 4. Patients also receive capecitabine orally (PO) twice daily (BID) followed by radiation therapy for 28 fractions on days 1-5 of weeks 8-13. Patients undergo resection surgery on weeks 21-25. After completion of study treatment, patients are followed up for 30 days and up to 5 years thereafter. ;
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