Talimogene Laherparepvec, Capecitabine, and Chemoradiation Before Surgery in Treating Patients With Locally Advanced or Metastatic Rectal Cancer
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|ClinicalTrials.gov Identifier: NCT03300544|
Recruitment Status : Recruiting
First Posted : October 3, 2017
Last Update Posted : July 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|Rectal Adenocarcinoma Stage III Rectal Cancer AJCC v7 Stage IIIA Rectal Cancer AJCC v7 Stage IIIB Rectal Cancer AJCC v7 Stage IIIC Rectal Cancer AJCC v7 Stage IV Rectal Cancer AJCC v7 Stage IVA Rectal Cancer AJCC v7 Stage IVB Rectal Cancer AJCC v7||Drug: Capecitabine Drug: Fluorouracil Other: Laboratory Biomarker Analysis Drug: Oxaliplatin Radiation: Radiation Therapy Biological: Talimogene Laherparepvec||Phase 1|
I. To determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of talimogene laherparepvec in combination with capecitabine and radiation in rectal cancer.
I. To establish safety and feasibility of the combination including complications from surgical resection II. To determine the neoadjuvant rectal (NAR) score of talimogene laherparepvec with chemotherapy and radiation.
I. To correlate genomic information including RAS, RAF mutation status with response, disease free survival (DFS) and/or overall survival (OS).
II. To determine immunodulatory 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, 2-4, and 8-9. Patients receive capecitabine orally (PO) twice daily (BID), fluorouracil intravenously (IV) over 46 hours, oxaliplatin IV over 2 hours followed by radiation therapy for 28 fractions on weeks 2-5 and 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Talimogene Laherparepvec (Talimogene Laherparepvec) With Neoadjuvant Chemotherapy and Radiation in Adenocarcinoma of the Rectum|
|Actual Study Start Date :||September 20, 2017|
|Estimated Primary Completion Date :||July 31, 2019|
|Estimated Study Completion Date :||July 31, 2019|
Experimental: Treatment (T-VEC, capecitabine, chemoradiation)
Patients receive talimogene laherparepvec intralesionally via endoscopy on weeks 1, 2-4 and 8-9. Patients receive capecitabine PO BID, fluorouracil IV over 46 hours, oxaliplatin IV over 2 hours followed by radiation therapy for 28 fractions on weeks 2-5 and 8-13. Patients undergo resection surgery on weeks 21-25.
Other: Laboratory Biomarker Analysis
Radiation: Radiation Therapy
Biological: Talimogene Laherparepvec
- Maximum tolerated dose (MTD) of talimogene laherparepvec (TVEC) in combination with capecitabine and radiation assessed using the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0 [ Time Frame: 4 weeks after surgery ]
- Incidence of dose limiting toxicities (DLTs) of TVEC defined as grade 3 or 4 toxicities assessed using the NCI CTCAE version 5.0 [ Time Frame: 4 weeks after surgery ]
- Percent of planned dose intensity [ Time Frame: Up to 5 years ]Descriptive statistics will be used to report results.
- Pathological complete response (pCR) [ Time Frame: Up to 5 years ]Will be reported with proportions along with the appropriate confidence intervals.
- Disease free survival (DFS) [ Time Frame: Up to 5 years ]Will be reported using Kaplan-Meier method.
- Overall survival (OS) [ Time Frame: Up to 5 years ]Will be reported using Kaplan-Meier method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03300544
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Site Public Contact 877-312-3961|
|Principal Investigator: Nageshwara V. Dasari|
|Principal Investigator:||Nageshwara Dasari||University of Texas MD Anderson Cancer Center LAO|