Colorectal Cancer, Pancreas Cancer
Conditions
Keywords
Maintenance therapy, Adjuvant Therapy
Brief summary
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
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.
Interventions
DRUGDovitinib
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
Sponsors
Novartis
Georgetown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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-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. 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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biomarker Discovery | 2 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 2 years | 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 |
| Safety | 2 years | Percent of subjects who experience grade 3/ 4 adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dovitinib Dovitinib 500 mg orally daily for 5 days followed by 2 days off (7 day cycles) for up to 2 years
Dovitinib: 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. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lack of Efficacy | 4 |
Baseline characteristics
| Characteristic | Dovitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 50.9 years |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 5 / 9 |
Outcome results
Primary
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
Time frame: 2 years
Population: Data cannot be summarized in the data table because biomarker analysis did not take place after study closure due to insufficient number of samples to yield significant results related to dovitinib administration. Instead, collected samples are stored in our biobank, as consented by all patients, for future Oncological analyses of importance.
Secondary
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
Time frame: 2 years
Population: Patients had either Stage 4 Colon Cancer, post-metastasectomy; Stage 4 Colon Cancer post-initial chemotherapy; Pancreas Cancer, post-resection and adjuvant chemo; or Locally advanced pancreas cancer post-chemo and radiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dovitinib | Progression-free Survival | 46 days |
Secondary
Safety
Percent of subjects who experience grade 3/ 4 adverse events
Time frame: 2 years
Population: Patients had either Stage 4 Colon Cancer, post-metastasectomy; Stage 4 Colon Cancer post-initial chemotherapy; Pancreas Cancer, post-resection and adjuvant chemo; or Locally advanced pancreas cancer post-chemo and radiation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dovitinib | Safety | 56 percentage of participants |