Maintenance Dovitinib for Colorectal and Pancreas Cancer

Study Overview
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Brief Summary
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This study is for patients with stage 4 colon cancer who have had initial chemotherapy or had surgery to remove metastases and patients with pancreas cancer, which has been surgically removed and are receiving adjuvant chemotherapy or is locally advanced and have already received chemotherapy and radiation. The purpose of this study is to determine the effects of oral dovitinib in patients with advanced stage colorectal and pancreas. Effects include biomarker changes, progression-free survival and safety. Dovitinib will be taken by mouth for 5 days out of every week for up to 2 years.

Detailed Description
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This is a single institution, nonrandomized, open-label pilot study of dovitinib as maintenance and adjuvant therapy in patients with colorectal and pancreas cancers. Patient Populations: Cohort 1: Stage 4 Colon Cancer s/p metastasectomy (Adjuvant cohort) Cohort 2: Stage 4 Colon Cancer after initial chemotherapy (Maintenance cohort) Cohort 3: Pancreas Cancer s/p resection and adjuvant chemo (Adjuvant cohort) Cohort 4: Locally advanced pancreas cancer s/p chemo and radiation (Maintenance cohort) Each of the 4 cohorts will be accrued independently. 15 patients will be accrued to each cohort. Treatment will begin following the completion of the standard adjuvant or induction therapy. Patients will continue to take dovitinib until they demonstrate progression of disease using standard RECIST criteria, withdraw consent, or experience unacceptable toxicity. Blood and urine Biomarker studies will be performed on all patients in all cohorts. Samples will be collected at baseline and every 8 weeks for the first 6 months and then every 3 months thereafter, while patients are on study. Blood and urine will be collected and banked for protein, miRNA and metabolomic analysis. Tumor specimens will be taken from patients in maintenance cohorts before and 2 weeks after initiation of dovitinib. All of these samples will be analyzed to determine if biomarkers of benefit and progression can be determined.

Official Title
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A Pilot Study of Dovitinib as Maintenance and Adjuvant Therapy in Patients With Colorectal and Pancreas Cancers

Conditions
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Colorectal Cancer, Pancreas Cancer

Intervention / Treatment
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* Drug: Dovitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a confirmed diagnosis of: Stage 4 colon cancer either s/p metastasectomy or post-initial chemotherapy or maintenance standard of care, either involving 5-fluorouracil/leucovorin (5-FU/LV) alone or continual bevacizumab alone. Patients in maintenance cohort must have had 2 consecutive CT scans showing stable disease and not be experiencing significant prior treatment-related toxicity above Grade 1. Pancreas cancer, either s/p resection and adjuvant chemotherapy or locally advanced pancreas cancer s/p chemotherapy and radiation. Initial chemotherapy or radiation therapy may have been stopped between 2 weeks and 2 months prior to study start, and patients must have recovered from prior treatment related toxicity to grade 1 or less. Prior surgery, including tumor resection or metastasectomy must have been performed at least 4 weeks prior to study enrollment. No concomitant anti-cancer treatment is allowed Age >/= 18 years Performance status of 0-1 Adequate hepatic, bone marrow, and renal function Partial thromboplastin time (PTT) must be </= 1.5 x upper normal limit of institution's normal range and INR (International Normalized Ratio) < 1.5. Life expectancy >/= 4 months for maintenance cohorts and >/= 6 months for adjuvant cohorts Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and must not be lactating. Subject is capable of understanding and complying with protocol demands and able to sign and date the informed consent Exclusion Criteria: Women of child-bearing potential, who are biologically able to conceive, not employing two forms of highly effective contraception or who are pregnant. Women who are breast-feeding Fertile males unwilling to use contraception Patients with brain metastases or any history of brain metastases Patients who have undergone major surgery (e.g., intra-thoracic, -abdominal, or -pelvic) </= 4 weeks prior to starting study treatment or who have not recovered from such therapy Patients with a history of pulmonary embolism, or untreated deep vein thrombosis within the past 6 months Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib The subject has had another active malignancy within the past 5 years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Patients who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies </= 2 weeks prior to starting the study drug, or who have not recovered from the side effects of such therapy Cirrhosis, chronic active hepatitis or chronic persistent hepatitis Patients who are currently receiving prasugrel No concurrent use of isoniazid, labetolol, trovafloxacin, tolcapone, and felbamate No concurrent use of other investigational drugs or antineoplastic therapies. Patients with impaired cardiac function or clinically significant cardiac diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dovitinib<br>Dovitinib 500 mg orally daily for 5 days followed by 2 days off (7 day cycles) for up to 2 years | Drug: Dovitinib<br>* All patients in the study will receive Dovitinib, 500 mg orally daily for 5 days followed by 2 days off (7 day cycles) for up to 2 years. If 500 mg is intolerable, 400 mg will be dosed. If 400 mg is intolerable, 300 mg will be dosed<br>* Other names: TKI258;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker Discovery | Changes in biomarkers from before treatment compared to during or after treatment: expression of pFGFR, pFRS2, pERK, BFGF, VEGF, FGFR1, FGFR2,VEGFR, Ki-67, Asp175, and CA9 in tumor tissue; FGFR, VEGFs, BFGF, PLGF, sVEGFR1/ 2, FGF23, GCSF, PDGF-AB, SDF-1a and SCF levels in serum | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Time in days from study entry until disease progression or death Disease progression was defined according to RECIST as at least a 20% increase in the sum of the longest diameter of the target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one or more new lesions | 2 years | 
| Safety | Percent of subjects who experience grade 3/ 4 adverse events | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maintenance therapy, Adjuvant Therapy