Capecitabine and Lenvatinib With External Radiation in Rectal Adenocarcinoma
Phase I Study of Pre-operative Capecitabine and Lenvatinib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma
1 other identifier
interventional
20
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2016
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 12, 2016
CompletedStudy Start
First participant enrolled
October 14, 2016
CompletedFirst Posted
Study publicly available on registry
October 17, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 11, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
May 14, 2020
CompletedMay 31, 2022
May 1, 2022
3 years
October 12, 2016
May 27, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose (MTD)
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 Outcomes (2)
Rate of Pathologic Response
Up to 36 months
Occurrence of Treatment Related Adverse Events
Up to 36 months
Other Outcomes (2)
Rate of Potential Biomarkers for Vascular Endothelial Growth Factor (VEGF)
Up to 36 months
Radiosensitivity Index (RSI)
Up to 36 months
Study Arms (1)
Pre-Surgery Chemotherapy/Radiotherapy
EXPERIMENTALPre-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.
Interventions
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.
Pre-surgery Capecitabine, 850 mg/m\^2, twice a day (BID) on days 1-5 for 5½ -6 weeks.
Pre-surgery RT: Participants will receive 6 weeks of radiation therapy. The radiation sessions will be daily, Monday through Friday, except for holidays.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Related Publications (1)
Mehta R, Frakes J, Kim J, Nixon A, Liu Y, Howard L, Martinez Jimenez ME, Carballido E, Imanirad I, Sanchez J, Dessureault S, Xie H, Felder S, Sahin I, Hoffe S, Malafa M, Kim R. Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma. Oncologist. 2022 Aug 5;27(8):621-e617. doi: 10.1093/oncolo/oyac003.
PMID: 35325225DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Richard Kim, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 12, 2016
First Posted
October 17, 2016
Study Start
October 14, 2016
Primary Completion
October 11, 2019
Study Completion
May 14, 2020
Last Updated
May 31, 2022
Record last verified: 2022-05