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The main purpose of this study is to evaluate the safety and efficacy of Apatinib in combination with Gefitinib as compared to placebo in combination with Gefitinib in participants with stage ⅢB-IV Non-squamous non-small-cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). Safety and tolerability of Apatinib in combination with Gefitinib will be assessed in the first portion (Part A) before proceeding to the second portion of this study (Part B).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gefitinib + Apatinib | Experimental | (Part A) Phase I, Open-label, Dose-escalation Study Escalating doses(500mg, 750mg, or 250mg) of Apatinib in combination with 250mg Gefitinib daily orally. Participants may continue to receive treatment until progress or intolerable. (Part B)Multicenter, Randomized, Double-Blind Study Apatinib (dose determined from Part A of study) in combination with 250mg Gefitinib. |
|
| Gefitinib + Placebo | Placebo Comparator | (Part A) Not Applicable (Part B) Placebo in combination with 250mg Gefitinib. Participants may continue to receive treatment until progress or intolerable. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apatinib | Drug | Patients will be treated with Apatinib, 250/500/750 mg(dose determined from Part A of study) p.o., daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| (Part A) Determine Dose-Limiting Toxicity (DLT) of Apatinib in combination with Gefitinib | Determine the safety, tolerability and DLTs of Apatinib in Combination With Gefitinib | 1 months |
| (Part A) Maximum Tolerated Dose (MTD) of Apatinib in Combination With Gefitinib | MTD was determined by testing increasing doses up to 750 mg daily (qd) on dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (= Dose Limiting Toxicity (DLT) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria (CTC) Grade 4 Neutropenia in specific conditions, platelets < 25,000 cells/mL; specific non-hematologic/biochemical toxicities CTC Grade 3 or 4; additionally, any toxicity considered by the investigator severe enough was designated a DLT); CTC Version 2 were used. | 1 months |
| (Part B) Progression Free Survival (PFS) | Time from the date of enrolment until documented progression or death, whichever occurs first. | Randomization to Measured Progressive Disease or Death from Any Cause (Estimated as 42 Months) |
| Measure | Description | Time Frame |
|---|---|---|
| (Part B) Overall Survival (OS) | Time from the date of enrolment until death from any cause. | Randomization to Date of Death from Any Cause (Estimated as 50 Months) |
| (Part B) Objective Response Rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hongyun Zhao | Contact | 86-20-8734 2482 | zhaohy@sysucc.org.cn |
| Name | Affiliation | Role |
|---|---|---|
| Hongyun Zhao | Sun Yat-Sen University Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Center | Recruiting | Guangzhou | Guangdong | 510000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34033974 | Derived | Zhao H, Yao W, Min X, Gu K, Yu G, Zhang Z, Cui J, Miao L, Zhang L, Yuan X, Fang Y, Fu X, Hu C, Zhu X, Fan Y, Yu Q, Wu G, Jiang O, Du X, Liu J, Gu W, Hou Z, Wang Q, Zheng R, Zhou X, Zhang L. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. doi: 10.1016/j.jtho.2021.05.006. Epub 2021 May 24. | |
| 33067126 |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | May 5, 2022 | |
| Reset | Feb 3, 2023 |
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| Gefitinib | Drug | Patients will be treated with Gefitinib, 250 mg p.o., daily |
|
|
| Placebo | Drug |
|
Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment
| Randomization to Disease Progression (Estimated as 42 Months) |
| (Part B) Disease Control Rate (DCR) | Achievement of objective response or stable disease for at least 6 weeks | Randomization to Disease Progression (Estimated as 42 Months) |
| (Part B) Duration of Response (DoR) | Interval from the date of first documentation of objective response by RECIST to the date of first documented progression or relapse | Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Estimated as 42 Months) |
| (Part B) Time to progression disease (TTPD) | Time to progression disease | Randomization to Measured Progressive Disease (Estimated as 42 Months) |
| (Part B) Quality of Life (QoL) questionnaire | Baseline, End of Study (Estimated as 50 Months) |
| (Part A + B) Safety assessment : Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | including adverse events, physical examination, vital signs (including Blood Pressure(BP)), clinical chemistry and hematology | Randomization to Measured Progressive Disease (Estimated as 50 Months) |
| (Part A) Area Under roc Curve (last) | Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) Area Under roc Curve (tau) | Area under the plasma concentration time profile after single dose from time zero to the next dose | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) Cmax | Maximum observed plasma concentration | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) Tmax | Time for Cmax | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) t½a | Terminal half life | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) Ctrough | Predose concentration during multiple dosing | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) The Apparent Clearance(CL/F) | Apparent clearance | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) The Apparent Volume of Distribution (Vd/F) | Apparent volume of distribution | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) The Metabolite to Parent Ratio of Area Under roc Curve (tau) | Metabolite to parent ratio for Area Under roc Curve (tau) | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| (Part A) The Metabolite to Parent Ratio of Css,max(MRCmax) | Metabolite to parent ratio for Cmax | Apatinib & Gefitinib: Cycle1 Day 1 and 15 |
| Derived |
| Deng Z, Qin Y, Liu Y, Zhang Y, Lu Y. Role of Antiangiogenic Agents Combined With EGFR Tyrosine Kinase Inhibitors in Treatment-naive Lung Cancer: A Meta-Analysis. Clin Lung Cancer. 2021 Jan;22(1):e70-e83. doi: 10.1016/j.cllc.2020.08.005. Epub 2020 Sep 18. |
| 32508029 | Derived | Zhang Z, Zhang Y, Luo F, Ma Y, Fang W, Zhan J, Li S, Yang Y, Zhao Y, Hong S, Zhou T, Zhang Y, Zhao S, Huang Y, Zhao H, Zhang L. Dual blockade of EGFR and VEGFR pathways: Results from a pilot study evaluating apatinib plus gefitinib as a first-line treatment for advanced EGFR-mutant non-small cell lung cancer. Clin Transl Med. 2020 Jun;10(2):e33. doi: 10.1002/ctm2.33. Epub 2020 Jun 4. |
| 31699150 | Derived | Zhang Z, Luo F, Zhang Y, Ma Y, Hong S, Yang Y, Fang W, Huang Y, Zhang L, Zhao H. The ACTIVE study protocol: apatinib or placebo plus gefitinib as first-line treatment for patients with EGFR-mutant advanced non-small cell lung cancer (CTONG1706). Cancer Commun (Lond). 2019 Nov 7;39(1):69. doi: 10.1186/s40880-019-0414-4. |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| May 5, 2022 | Feb 3, 2023 |
| ID | Term |
|---|---|
| C553458 | apatinib |
| D000077156 | Gefitinib |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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