A Pilot Study of Dovitinib as Maintenance and Adjuvant Therapy in Patients With Colorectal and Pancreas Cancers
- Patients with a confirmed diagnosis of:
1. Stage 4 colon cancer either s/p metastasectomy or post-initial chemotherapy or
maintenance "standard of care", either involving 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.
2. 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 chemotherapy and radiation is allowed as defined above.
- 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
- 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 parameters as outlined in the
protocol and able to sign and date the informed consent
- 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 not willing to use contraception
- Patients with brain metastases or any history of brain metastases
- Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal, or
intra-pelvic) = 4 weeks prior to starting study treatment or who have not recovered
from side effects of 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
- Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- Patients who are currently receiving prasugrel
- Concurrent use of isoniazid, labetolol, trovafloxacin, tolcapone, and felbamate are
- Concurrent use of other investigational drugs is not permitted.
- The administration of other antineoplastic therapy is not permitted
- Anticipated patient survival under 4 months for maintenance cohorts and 6 months for
- Patients with any of the following concurrent severe and/or uncontrolled medical
conditions which could compromise participation in the study. Impaired cardiac
function or clinically significant cardiac diseases, including any of the following:
1. History or presence of serious uncontrolled ventricular arrhythmias
2. Clinically significant resting bradycardia
3. LVEF assessed by 2-D echocardiogram < 50% or lower limit of normal (whichever is
higher) or multiple gated acquisition scan < 45% or lower limit of normal
(whichever is higher)
4. Any of the following within 6 months prior to starting study treatment:
myocardial infarction, severe/unstable angina, coronary artery bypass graft,
congestive heart failure, cerebrovascular accident, transient ischemic attack
5. Uncontrolled hypertension defined by a SBP >/= 160 mm Hg and/or DBP >/= 100 mm
Hg, with or without anti-hypertensive medication. Initiation or adjustment of
antihypertensive medication(s) is allowed prior to study entry.
- Life-threatening visceral disease or other severe concurrent disease
- Patients receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to dovitinib.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with