Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer

NCT01531777 | Completed Phase 2 DMC

• 1 other identifier: APTN-II-CRC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable. PURPOSE:

1. 1.Studying how well Apatinib works in treating patients.
2. 2.Finding the efficacy and safety of 500 mg or 750mg Apatinib.
3. 3.Pharmacokinetics/Pharmacodynamics(PK/PD).
4. 4.Exploring new outcome measures of antiangiogenic drugs.

Conditions

Colorectal Cancer

Keywords

Advanced Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• ORR (Objective Response Rate)

  12 weeks

Secondary Outcomes (4)

• DCR (Disease Control Rate)

  12 weeks after treatment

• PFS

  3 years

• OS (Overall Survival)

  3 years

• QoL (Quality of Life)

  3 years

Study Arms (2)

Apatinib 500mg

EXPERIMENTAL

500mg,p.o.,qd

Drug: Apatinib

Apatinib 750mg

EXPERIMENTAL

750mg,p.o.,qd

Drug: apatinib

Interventions

apatinib DRUG

500 mg,p.o.,qd, until disease progression or intolerable toxicity or patients withdrawal of consent.

Apatinib 500mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 and ≤ 70 years of age
• Histological confirmed advanced or metastatic colorectal Cancer，at least one measurable lesion, larger than 10 mm in diameter by spiral CT scan(scanning layer ≤ 5 mm )
• Have failed for ≥ 2 lines of chemotherapy
• Life expectancy of more than 3 months
• ECOG performance scale ≤ 1
• Duration from the last therapy is more than 6 weeks for nitroso or mitomycin More than 4 weeks for operation, radiotherapy or cytotoxic agents
• Adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 10E+9/L, neutrophil \> 1.5 × 10E+9/L, serum creatinine ≤ 1×upper limit of normal(ULN), bilirubin \< 1.25 ULN, and serum transaminase ≤ 2.5× ULN)
• Child bearing potential, a negative urine or serum pregnancy test result before initiating apatinib, must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article.
• Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.

You may not qualify if:

• History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
• Pregnant or lactating women
• Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite using single medical therapy, more than class I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia(including QTcF:male ≥ 450 ms, female ≥ 470 ms), or cardiac insufficiency myocardial ischemia, arrhythmia, or cardiac insufficiency
• Before or at the same time any, second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
• Any factors that influence the usage of oral administration Evidence of CNS metastasis
• URT: urine protein ≥ (++)and \> 1.0 g of 24 h
• PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation
• Abuse of drugs
• Certain possibility of gastric or intestine hemorrhage
• Less than 4 weeks from the last clinical trial
• Viral hepatitis type B or type C
• Prior VEGFR inhibitor treatment
• Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead
• Fudan University: collaborator

Study Sites (1)

Fudan University cancer hospital

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

apatinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Jin Li, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2012
• First Posted: February 13, 2012
• Study Start: April 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 3, 2015

Record last verified: 2012-02

Locations

CN (1)