| Eligibility |
Inclusion Criteria
1. Provision of informed consent prior to any study specific procedures, sampling and
analyses.
2. Male or female, age18-75 years.
3. Pathologically confirmed unresectable locally advanced or advanced metastatic
colorectal adenocarcinoma .
4. The patient had previously failed standard first-line systemic chemotherapy,Prior
adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy,
investigational agents) if 6 months or more have passed since completion of therapy.
5. A WHO performance status equal to 0-1 with no deterioration over the previous 2 weeks
and a minimum life expectancy of 12 weeks.
6. At least 1 lesion that has not previously been irradiated, that has not been chosen
for biopsy during the study screening period, and that can be accurately measured at
Baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short
axis = 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI),
whichever is suitable for accurately repeated measurements. If only one measurable
lesion exists, it is acceptable to be used (as a target lesion) as long as it has not
been previously irradiated and baseline tumour assessment scans are done at least
14days afar the screening biopsy is performed.
7. Inadequate bone marrow reserve or organ function, as demonstrated by any of the
following laboratory values:
1. Absolute neutrophil count (ANC) =1.5×109/L
2. Platelet count =100×109 / L
3. Hemoglobin=90 g/L(<9 g/dL)
4. Alanine aminotransferase =2.5 × upper limit of normal (ULN) if no demonstrable
liver metastases or = 5 × ULN in the presence of liver metastases.
5. Aspartate aminotransferase (AST) = 2.5 × ULN if no demonstrable liver metastases
or = 5 × ULN in the presence of liver metastases.
6. Total bilirubin (TBL)= 1.5 × ULN if no liver metastases or = 3 × ULN in the
presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or
liver metastases.
7. Creatinine= 1.5 × ULN concurrent with creatinine clearance =50 mL/min (measured
or calculated by the Cockcroft-Gault equation); confirmation of creatinine
clearance is only required when creatinine is =1.5 × ULN.
8. Females should be using adequate contraceptive measures throughout the study; should
not be breastfeeding at the time of screening, during the study and until 3 months
after completion of the study; and must have a negative pregnancy test prior to start
of dosing if of childbearing potential or must have evidence of non-childbearing
potential by fulfilling 1 of the following criteria at Screening:
1. Postmenopausal defined as age more than 50 years and amenorrheic for at least 12
months following cessation of all exogenous hormonal treatments.
2. Women under 50 years old would be considered postmenopausal if they have been
amenorrheic for 12 months or more, following cessation of exogenous hormonal
treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone
(FSH) levels in the postmenopausal range for the laboratory.Documentation of
irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or
bilateral salpingectomy, but not by tubal ligation. Male patients should be
willing to use barrier contraception (i.e., condoms).
3. For inclusion in study, patient must provide a written informed consent.
Exclusion Criteria:
1. Treatment with any of the following:
1. Prior treatment with Surufatinib .
2. Major surgery (excluding placement of vascular access) within 4 weeks of the
first dose of study drug.
3. Radiotherapy with a limited field of radiation for palliation within 4 week of
the first dose of study drug, with the exception of patients receiving radiation
to > 30% of the bone marrow or with a wide field of radiation within 4 weeks of
the first dose of study drug.
2. Patients with other malignancies, except basal cell carcinoma and carcinoma in situ..
3. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria
for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the
exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
4. Spinal cord compression or brain metastases unless asymptomatic, stable, and not
requiring steroids for at least 2 weeks prior to start of study treatment.
5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes
it undesirable for the patient to participate in the trial OR which would jeopardize
compliance with the protocol such as active infection. Screening for chronic
conditions is not required.
6. Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to
swallow the study drug, or previous significant bowel resection that would preclude
adequate absorption of Surufatinib.
7. Any of the following cardiac criteria:
1. Mean resting corrected QT interval (QTc) > 470 ms obtained from 3
electrocardiograms (ECGs), using the screening clinic's ECG machine and
Fridericia's formula for QT interval correction (QTcF).
2. Any clinically important abnormalities in rhythm, conduction, or morphology of
the resting ECG (e.g., complete left bundle branch block, third-degree heart
block, second-degree heart block, PR interval > 250 ms).
3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events, such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or unexplained sudden death under 40 years of age in
first degree relatives or any concomitant medication known to prolong the QT
interval.
4. Left ventricular ejection fraction (LVEF) = 40%.
8. Past medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis that required steroid treatment, or any evidence of
clinically active interstitial lung disease.
9. Women who are breastfeeding or have a positive urine or serum pregnancy test at the
Screening Visit.
10. History of hypersensitivity to any active or inactive ingredient of Surufatinib or to
drugs with a similar chemical structure or class to Surufatinib.
11. Patients who are allergic to paclitaxel or other drugs prepared with polyoxyethyl
castor oil, carboplatin or other platinum containing compounds.
Patients with contraindications of Chemotherapy .
12. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions, and
requirements.
13. Any disease or condition that, in the opinion of the Investigator, would compromise
the safety of the patient or interfere with study assessments.
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