Safety and Efficacy of Anlotinib in Combination With Irinotecan in Patients With Pretreated Advanced Colorectal Cancer

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Colo-rectal Cancer

Treatments

Drug: Anlotinib Hydrochloride with Irinotecan

Study type

Interventional

Funder types

Other

Identifiers

NCT03545711

NCC201803012

Details and patient eligibility

About

Patients with pretreated advanced colorectal cancer are recruited to the phase I portion of this prospective non-randomised study in an escalated dose cohort. The primary endpoint of the dose-escalation phase is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of anlotinib when given in combination with irinotecan. The phase II (dose-expansion) portion is designed to characterize the safety and potential efficacy of the combination therapy in pretreated advanced colorectal cancer patients.

Enrollment

42 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

willing and able to provide written informed consent and comply with the requirements of the study
histologically- or cytologically-confirmed advanced colorectal cancer
failed or intolerable to at least one prior therapy
have evidence of measurable disease per RECIST v1.1
Eastern Collaborative Oncology Group (ECOG) Performance Status ≤ 1
weight ≥40kg
life expectancy >12 weeks

Exclusion criteria

Subjects meeting any of the following criteria are ineligible for participation in the study:

history of any anti-cancer therapy (including investigational agents) within 28 days prior to study entry
presence of toxicity of prior anti-cancer therapy that has not resolved to Grade 1, as determined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
symptomatic brain metastasis requiring active treatment
any previous malignancy, except for non squamous-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix within 5 years prior to study entry
active or clinically unstable infection requiring systemic therapy
unable to swallow oral medications or with gastrointestinal disorders that might interfere with proper absorption of oral drugs
active digestive ulcer disease, inflammatory bowel disease, intestinal obstruction or any other condition that, in the clinical judgment of the Principal Investigator, may cause severe gastrointestinal bleeding or perforation
unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event ≤2 months prior to study entry
history of stroke or transient ischemic attack (TIA) within 12 months prior to study entry
any of the following abnormal findings in organ or marrow function 1 week prior to study entry:
- Leukocytes < 1.5*10^9/L, or Platelets < 100*10^9/L, or Hb< 90g/L
- Total bilirubin > 1.5 × institutional upper limit of normal (ULN), or AST (aspartate amino transferase)/ALT (alanine amino transferase)> 3 × institutional ULN for liver metastases, > 1.5 × institutional ULN in case of no liver metastases
- any electrolyte imbalance of clinical significance
- creatinine > institutional ULN and creatinine clearance < 60 mL/min
- spot urine protein ≥(2+) or 24-hour proteinuria ≥1.0g/24h
- APTT (activated partial thromboplastin time) or INR (international normalized ratio for prothrombin time) > 1.5 × institutional ULN
treatment refractory hypertension defined as a blood pressure of systolic> 140 millimeter of mercury (mm Hg) and/or diastolic > 90 mm Hg which cannot be controlled by a single anti-hypertensive agent
LVEF (left ventricular ejection fraction ) <50%
history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft within 6 months prior to study entry, or history or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association (NYHA)
present with non-healing fractures of bone or wounds of skin
pregnant or lactating female
sexually active female (of childbearing potential) or male unwilling to adopt an effective method of birth control during the course of the study
serious and/or unstable pre-existing psychiatric disorder
familial, sociological or geographical conditions that, in the clinical judgment of the Principal Investigator, do not permit compliance with the protocol
known immediate or delayed hypersensitivity reaction to anlotinib, irinotecan or their excipients
administration of irinotecan in prior treatments