- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02935309
Capecitabine and Lenvatinib With External Radiation in Rectal Adenocarcinoma
May 27, 2022 updated by: H. Lee Moffitt Cancer Center and Research Institute
Phase I Study of Pre-operative Capecitabine and Lenvatinib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma
This research study is designed to see if Capecitabine and Lenvatinib in combination with external radiation therapy are effective in treating locally advanced rectal adenocarcinoma in patients who have not yet had surgery, and what the best dosage is.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically (archival tissue) confirmed adenocarcinoma of the rectum that begins within 12 cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy with no evidence of distant metastasis.
- Locally advanced rectal cancer determined by any of the following features: 1.) Fixed or immobile tumor on physical exam and/or; 2.) T3 disease with invasion through the muscularis propria as defined by transrectal ultrasound, CT or MRI; 3.) T4 disease with invasion of adjacent structures such as pelvic sidewall, sacrum, pelvis, bladder and/or prostate as determined appropriate imaging modalities such as ultrasound, CT or MRI; 4.) Any T with + N on CT scan/MRI or transrectal ultrasound.
- Age equal to or greater than 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
- Adequate bone marrow, liver and renal function.
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least 3 months after the last administration of lenvatinib.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
Exclusion Criteria:
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Participants must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Previous pelvic irradiation therapy.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
- Active clinically serious infection > CTCAE Grade 2.
- Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic, attacks, deep vein thrombosis (DVT) within the past 6 months.
- Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. (Treatment with low molecular weight heparin (LMWH) is allowed).
- Active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated non-pelvic cancer from which the patient has been continuously disease free more than 3 years.
- Marked baseline prolongation of QT/QTc interval (QTc interval ≥ 500 msec) using the Fridericia method (QTc = QT/RR0.33) for QTc analysis.
- Greater than 30 mg/dL on urine analysis. Patients with >30 mg/dL on urine analysis on urine analysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Patients with 24-hour protein ≥1 g/24 hours will be ineligible.
- Needing medical attention for serious bleeding in past 4 weeks.
- Previous chemotherapy except for antiangiogenic agent or tyrosine kinase inhibitor (TKI) will be allowed as long as it is more than 5 years.
- Major surgeries within 3 weeks of starting chemotherapy.
- Evidence or history of bleeding diathesis.
- Use of St. John's Wort or rifampin.
- Known or suspected allergy to lenvatinib or any agent given in the course of this trial.
- Any condition that impairs participant's ability to swallow whole pills.
- Any malabsorption problem.
- Medical need for the continued use of potent inhibitors/inducers of CYP3A4.
- Creatinine clearance not within study guidelines.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pre-Surgery Chemotherapy/Radiotherapy
Pre-surgery chemotherapy and external radiation therapy.
Dose escalation of Lenvatinib; fixed dose Capecitabine; Radiotherapy.
Lenvatinib and capecitabine will be started on day 1 with radiation and will be discontinued on the last day of radiation.
Surgical resection should occur between 6 - 10 weeks after the participant completes preoperative lenvatinib, capecitabine, and radiation therapy.
Postoperative chemotherapy after surgery will be given at investigator's discretion.
|
Pre-surgery Lenvatinib, days 1 - 5. Dose Escalation Levels: 1.) 10 mg by mouth (PO) daily (QD); 2.) 14 mg PO QD; 3.) 20 mg PO QD; 4.) 24 PO QD.
Other Names:
Pre-surgery Capecitabine, 850 mg/m^2, twice a day (BID) on days 1-5 for 5½ -6 weeks.
Other Names:
Pre-surgery RT: Participants will receive 6 weeks of radiation therapy.
The radiation sessions will be daily, Monday through Friday, except for holidays.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: Up to 6 months
|
MTD of lenvatinib used in combination with capecitabine and external beam radiation as neoadjuvant therapy for patients with locally advanced rectal carcinoma.
The MTD of lenvatinib will be defined as the highest dose level at which no more than 1 out of 6 participants experiences dose-limiting toxicity (DLT).
DLT: Any of the hematology or non-hematologic toxicities noted in Table 3 of the protocol, considered to be at least possibly related to lenvatinib and/or capecitabine.
|
Up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Pathologic Response
Time Frame: Up to 36 months
|
Pathologic response rate after pre-operative therapy and surgery.
Pathologic Complete Response (pCR) will be defined as pathologic proof of a complete response based on histologic evaluation of the resected specimen.
|
Up to 36 months
|
Occurrence of Treatment Related Adverse Events
Time Frame: Up to 36 months
|
To further define safety profile of the combination.
Adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0.
|
Up to 36 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Potential Biomarkers for Vascular Endothelial Growth Factor (VEGF)
Time Frame: Up to 36 months
|
Investigators will identify potential biomarkers for VEGF pathway and attempt to correlate with pCR.
The associations of the potential biomarkers and radiosensitivity index (RSI) with pCR will be examined using logistic regression.
A two-sided p-value of <0.05 will be considered statistically significant.
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Up to 36 months
|
Radiosensitivity Index (RSI)
Time Frame: Up to 36 months
|
To determine if low radiosensitivity index (RSI) will correlate with pathologic complete response (pCR).
pCR will be examined using logistic regression.
A two-sided p-value of <0.05 will be considered statistically significant.
|
Up to 36 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 14, 2016
Primary Completion (Actual)
October 11, 2019
Study Completion (Actual)
May 14, 2020
Study Registration Dates
First Submitted
October 12, 2016
First Submitted That Met QC Criteria
October 13, 2016
First Posted (Estimate)
October 17, 2016
Study Record Updates
Last Update Posted (Actual)
May 31, 2022
Last Update Submitted That Met QC Criteria
May 27, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Adenocarcinoma
- Rectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Capecitabine
- Lenvatinib
Other Study ID Numbers
- MCC-18646
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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