Apatinib Versus Placebo as a Third Line Treatment in Patients With Advanced or Metastatic Gastric Cancer

• ClinicalTrials.gov Identifier: NCT00970138
• Recruitment Status: Completed
• First Posted: September 2, 2009
• Last Update Posted: July 12, 2011
• Sponsor: Fudan University
• Information provided by: Fudan University

Study Description

Brief Summary:

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 and the maximum tolerable daily dose is 850 mg. The purpose of this study is to determine whether apatinib can improve progression free survival compared with placebo in patients with metastatic gastric carcinoma who failed two lines of chemotherapy.

Condition or disease	Intervention/treatment	Phase
Gastric Carcinoma	Drug: apatinib tablet	Phase 2; Phase 3

Detailed Description:

Up to now, although FU based, cisplatin based and taxane based regimen, and ECF regimen have been suggested as the first line therapy for A/MGC by FDA, the efficacy of these treatment is still unsatisfied for their toxicity and limitation in prolonging survival. Based on the promising results of apatinib in the phase I study, this clinical trial has been designed to evaluate whether apatinib can improve progression free survival in patients with metastatic gastric carcinoma who failed two lines of chemotherapy compared with placebo. Patients will be randomized to 3 groups, one group patients will receive the treatment of apatinib 850mg qd, one group patients will receive apatinib 425mg bid, and the other group will receive placebo.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2/3 Study of Apatinib as Third Line Treatment in Patients With Metastatic Gastric Carcinoma
• Study Start Date: June 2009
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: December 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: A 850; apatinib 850 mg qd, and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent	Drug: apatinib tablet; A850: apatinib 850 mg qd p.o. plus placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent B425: apatinib 425 mg bid p.o. until disease progression or intolerable toxicity or patients withdrawal of consent Cpla: placebo bid p.o. until disease progression or intolerable toxicity or patients withdrawal of consent
Experimental: B 425; apatinib 425 mg bid, and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent	Drug: apatinib tablet; A850: apatinib 850 mg qd p.o. plus placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent B425: apatinib 425 mg bid p.o. until disease progression or intolerable toxicity or patients withdrawal of consent Cpla: placebo bid p.o. until disease progression or intolerable toxicity or patients withdrawal of consent
Placebo Comparator: C pla; placebo bid, and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent	Drug: apatinib tablet; A850: apatinib 850 mg qd p.o. plus placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent B425: apatinib 425 mg bid p.o. until disease progression or intolerable toxicity or patients withdrawal of consent Cpla: placebo bid p.o. until disease progression or intolerable toxicity or patients withdrawal of consent

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: 8 weeks ]

Secondary Outcome Measures :

1. Overall survival safety [ Time Frame: 8 weeks ]
2. DCR (Disease control rate) [ Time Frame: 8 weeks ]
3. ORR (Objective response rate) [ Time Frame: 8 weeks ]
4. QoL (Quality of life) [ Time Frame: 8 weeks ]
5. Toxicity [ Time Frame: 8 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• ≥ 18 and ≤ 70 years of age
• Histologically confirmed advanced or metastatic adenocarcinoma of the stomach
• Have failed for 2 lines of chemotherapy
• Life expectancy of more than 3 months
• ECOG performance scale ≤ 2
• At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan)
• Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
• More than 4 weeks for operation or radiotherapy
• More than 4 weeks for cytotoxic agents or growth inhibitors
• Adequate hepatic, renal, heart, and hematologic functions (platelets > 80 × 109/L, neutrophil > 2.0 × 109/L, serum creatinine ≤ 1.5mg/dl, total bilirubin within upper limit of normal(ULN), and serum transaminase≤2.5×the ULN).

Exclusion Criteria:

• Pregnant or lactating women
• History of other 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
• History of another malignancy within the last five years except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix
• Intercurrence with one of the following: hypertension, coronary artery disease, arrhythmia and heart failure
• Receiving the therapy of thrombolysis or anticoagulation
• Abuse of alcohol or drugs
• Allergy to the ingredient of the agent or more than two kinds of food and drug
• Less than 4 weeks from the last clinical trial
• Disability of serious uncontrolled intercurrence infection.

Contacts and Locations

Locations

China, Shanghai

Fudan University Cancer Hospital

ShangHai, Shanghai, China, 200032

Sponsors and Collaborators

Fudan University

Investigators

• Principal Investigator: Jin Li, MD, PHD; Fudan University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.

• Responsible Party: Jin Li/Dr, Fudan University cancer hospital
• ClinicalTrials.gov Identifier: NCT00970138
• Other Study ID Numbers: 2009APA-MGC
• First Posted: September 2, 2009
• Last Update Posted: July 12, 2011
• Last Verified: September 2010

Keywords provided by Fudan University:

Progress free survival; Toxicity; Response rate; Overall survival; Quality of live

Additional relevant MeSH terms:

Carcinoma; Stomach Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Apatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action