High-grade GliomaPhase 1/2NCT02848794
Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
A Phase 1/2 study testing Apatinib and Irinotecan in people with High-grade Glioma, run by The First People's Hospital of Lianyungang at 1 site in China.
Trial summary
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma. Read more about this study
- Who is it for?
- Ages 15 to 75 years
- Conditions the study is for
- High-grade Glioma
- What is being tested?
- Apatinib and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Jul 2016to Jul 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with histologically-confirmed, high-grade glioma(WHO Ⅲ/Ⅳ) who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery .
- With measurable or evaluable disease defined by RECIST 1.1 criteria by MRI scan.
- Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
- Life expectancy ≥3 months.
- No evidence of serious cardiopulmonary function damage, postoperative complication and hemorrhage on the baseline.
- No history of cerebral embolism, cerebral hemorrhage and serious hypertension disease.
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- Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas and mitomycin), radiotherapy and surgery.
- Patients have adequate organ function as defined by the following criteria:
- Hemoglobin (HGB) ≥90g/L
- Absolute neutrophil count (ANC) ≥1.5×109/L
- White blood cell (WBC) ≥3.0×109/L
- Platelet count ≥80×109/L
- Alanine aminotransferase(ALT) and Aspartate aminotransferase (AST) of ≤2.5 upper normal limitation (UNL) or ≤5 UNL in case of liver metastasis
- Creatinine (Cr) of ≤1.25 UNL or creatinine clearance(Ccr) > 45 ml/min.
- Patients will take contraceptive measures for the duration of the treatments and 8 weeks after the last treatment.
- With written informed consent signed voluntarily by patients themselves.
Who cannot join
- Pregnant or lactating women.
- Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications).
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- Coronary heart disease greater than ClassⅠ;Ⅰ-level arrhythmia (including QT interval prolongation≥440 ms) together with ClassⅠcardiac dysfunction
- Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction).
- Abnormal Coagulation (international normalized ratio>1.5, prothrombin time>UNL+4s,activated partial thromboplastin time>1.5 UNL), with tendency of bleeding.
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- Currently receive thrombolytic and anticoagulation therapy
- History of pneumorrhagia(CTCAE grade ≥2 ) or other parts hemorrhage(CTCAE grade ≥3 ) within 4 weeks prior to treatment.
- History of artery thrombosis and phlebothrombosis, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, within 6 month prior to treatment.
- Medical history of clinically significant thrombosis (bleeding or clotting disorder), excluding warfarin(1mg po qd) and aspirin(80-100mg po qd) for prevention under INR≤1.5.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First's People Hospital of Lianyungang
Lianyungang, Jiangsu, 222000
Xiaodong Jiang, Doctor, +86018961326201, jxdysy1970@163.com
Tao Yang, Master, +86018961327792, 18961327792@163.com
About this study
Official title: Phase I/IIa, Single-Arm, Open Study of Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
Read the detailed description
Gliomas account for almost 80% of primary malignant brain tumors, and glioblastoma is the most common subtype. Despite treatment with surgery, radiation, and chemotherapy(Temozolomide) almost all patients with glioma experience recurrence and the median survival for most patients is less than 2 years. In recurrent disease, salvage therapies have been limited and result in minimal improvement in OS. This overwhelming need for improved treatments has driven the development of novel drugs that target glioma biology, specifically anti-VEGF therapies.
Malignant gliomas are considered among the most angiogenic of cancers and are mostly fueled by vascular endothelial growth factor (VEGF) signaling via its endothelial tyrosine kinase receptor VEGF receptor 2 (VEGFR2). Levels of VEGF and its receptor are correlated with the histologic grade of gliomas, with the highest levels present in glioblastoma.Thus glioblastoma has emerged as an attractive tumor in which to conduct clinical trials of novel anti-VEGF agents, such as monoclonal antibodies and tyrosine kinase inhibitors.
Bevacizumab is a recombinant humanized monoclonal antibody that binds all VEGF isoforms, causing reduced tumor vascularization and inhibiting tumor growth. In a single-institute, phase II trial of patients with recurrent high-grade glioma, bevacizumab in combination with irinotecan demonstrated 46% 6-month PFS and 57% OR rates. Following on from the results of this study, another phase II trial was conducted to evaluate the safety and efficacy of bevacizumab alone and in combination with irinotecan, again showing promising results. On the basis this study, as well as a study by Kreisl and colleagues, FDA has approved to bevacizumab for patients with recurrent glioblastoma in 2009. Despite bevacizumab therapy, 6-month progression-free survival (PFS) for relapsed or progressive high-grade gliomas is 30.8% to 50.3%, and median overall survival (OS) is less than 42 week. Thus, recurrent high-grade gliomas remains a largely unmet medical need, which highlights the need for novel and effective therapies.
Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). Apatinib has been demonstrated as monotherapy prolongs OS in patients with gastric or gastroesophageal junction adenocarcinoma after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse events.
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
- Conditions
- High-grade Glioma
- Being tested
- Apatinib and Irinotecan
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apatinib and IrinotecanDrug
Patients were administered at apatinib (850mg po qd) and irinotecan(125mg/m2 d1,8) intravenously every three weeks for up to 6 cycles.Maintenance apatinib (500mg po qd) was administered until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Apatinib+Irinotecan | Experimental | Apatinib and irinotecan in treating patients with recurrent high-grade glioma,who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery . Receives: Drug: Apatinib and Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)
Measured: From enrollment to progression of disease. Estimated about 6 months
Secondary outcomes (6)
Overall Survival (OS)
The length of time from enrollment until the time of death (OS, overall survival)
Measured: From enrollment to death of patients. Estimated about 1 year
Objective Response Rate (ORR)
clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate)
Measured: From enrollment to 2 months after treatment
Disease Control Rate (DCR)
Disease control rate is defined as the number of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) based on RESIST v1.1 criteria.
Measured: From enrollment to 2 months after treatment
Duration of Response（DOR）
As measured by RECIST 1.1 criteria and defined as the time from the first documented CR or PR until disease progression or death from any cause.
Measured: From first documented CR or PR until disease progression or death(up to 1 year)
Quality of life (QOL)
Quality of life (QOL) will be measured using the EORTC QLQ-C30 questionnaires,which consists of 28 questions with answers that range from 1 (Not At All) to 4 (Very Much) and 2 questions that range from 1 (Very Poor) to 7 (Excellent)
Measured: up to 1 year
Incidence of treatment-related adverse events
The incidence of treatment-related adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionJul 2018 (estimated)
- Study completionJul 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for High-grade GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First People's Hospital of Lianyungang
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong Cancer Hospital and Institute, The Affiliated Hospital of Qingdao University, Yankuang Group General Hospital, Lianyungang Hospital Affiliated Bengbu Medical College, Suzhou Kowloon Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02848794
- Sponsor's protocol ID
- AI-001
- Status last verified
- Jun 2017
- First submitted
- 22 Jul 2016
- Last updated
- 16 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Wang L, Liang L, Yang T, Qiao Y, Xia Y, Liu L, Li C, Lu P, Jiang X. A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. Medicine (Baltimore). 2017 Dec;96(49):e9053. doi: 10.1097/MD.0000000000009053.
PubMed 29245310
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa, Single-Arm, Open Study of Apatinib and Irinotecan in Treating Patients With Recurrent High-grade Glioma
- ClinicalTrials.gov ID
- NCT02848794
- Acronym / sponsor ID
- AI-001
- Conditions
- High-grade Glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- The First People's Hospital of LianyungangUniversity, hospital or other
- Collaborators
- Shandong Cancer Hospital and Institute, The Affiliated Hospital of Qingdao University, Yankuang Group General Hospital, Lianyungang Hospital Affiliated Bengbu Medical College, Suzhou Kowloon Hospital
- Study start
- Jul 2016
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Jul 2018 (estimated)
- First posted
- 28 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
Detailed description
Gliomas account for almost 80% of primary malignant brain tumors, and glioblastoma is the most common subtype. Despite treatment with surgery, radiation, and chemotherapy(Temozolomide) almost all patients with glioma experience recurrence and the median survival for most patients is less than 2 years. In recurrent disease, salvage therapies have been limited and result in minimal improvement in OS. This overwhelming need for improved treatments has driven the development of novel drugs that target glioma biology, specifically anti-VEGF therapies.
Malignant gliomas are considered among the most angiogenic of cancers and are mostly fueled by vascular endothelial growth factor (VEGF) signaling via its endothelial tyrosine kinase receptor VEGF receptor 2 (VEGFR2). Levels of VEGF and its receptor are correlated with the histologic grade of gliomas, with the highest levels present in glioblastoma.Thus glioblastoma has emerged as an attractive tumor in which to conduct clinical trials of novel anti-VEGF agents, such as monoclonal antibodies and tyrosine kinase inhibitors.
Bevacizumab is a recombinant humanized monoclonal antibody that binds all VEGF isoforms, causing reduced tumor vascularization and inhibiting tumor growth. In a single-institute, phase II trial of patients with recurrent high-grade glioma, bevacizumab in combination with irinotecan demonstrated 46% 6-month PFS and 57% OR rates. Following on from the results of this study, another phase II trial was conducted to evaluate the safety and efficacy of bevacizumab alone and in combination with irinotecan, again showing promising results. On the basis this study, as well as a study by Kreisl and colleagues, FDA has approved to bevacizumab for patients with recurrent glioblastoma in 2009. Despite bevacizumab therapy, 6-month progression-free survival (PFS) for relapsed or progressive high-grade gliomas is 30.8% to 50.3%, and median overall survival (OS) is less than 42 week. Thus, recurrent high-grade gliomas remains a largely unmet medical need, which highlights the need for novel and effective therapies.
Apatinib is a small-molecule tyrosine kinase inhibitor (TKI) that highly selectively binds to and strongly inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). Apatinib has been demonstrated as monotherapy prolongs OS in patients with gastric or gastroesophageal junction adenocarcinoma after two or more lines of chemotherapy with moderate, reversible, and easily managed adverse events.
The study is aimed to evaluate the efficacy and safety of Apatinib and Irinotecan in patients with recurrent high-grade glioma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Apatinib+Irinotecan | Experimental | Drug: Apatinib and IrinotecanApatinib and irinotecan in treating patients with recurrent high-grade glioma,who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery . |
Who may qualify
- Ages
- 15 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with histologically-confirmed, high-grade glioma(WHO Ⅲ/Ⅳ) who have progressed on temozolomide, or radiotherapy alone, or combined with chemotherapy within 3 months after surgery .
- With measurable or evaluable disease defined by RECIST 1.1 criteria by MRI scan.
- Eastern Cooperative Oncology Group Performance Status (ECOG P.S.) of ≤ 2
- Life expectancy ≥3 months.
- No evidence of serious cardiopulmonary function damage, postoperative complication and hemorrhage on the baseline.
Key exclusion criteria (10 listed)
- Pregnant or lactating women.
- Inadequately controlled hypertension (defined as systolic blood pressure > 140 and/or diastolic blood pressure > 90 mmHg on antihypertensive medications).
- New York Heart Association (NYHA) Grade II or greater congestive heart failure.
- Coronary heart disease greater than ClassⅠ;Ⅰ-level arrhythmia (including QT interval prolongation≥440 ms) together with ClassⅠcardiac dysfunction
- Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Apatinib and IrinotecanPatients were administered at apatinib (850mg po qd) and irinotecan(125mg/m2 d1,8) intravenously every three weeks for up to 6 cycles.Maintenance apatinib (500mg po qd) was administered until disease progression or unacceptable toxicity. | Drug | Apatinib+Irinotecan |
Primary outcome
Progression-Free Survival (PFS)
Time frame: From enrollment to progression of disease. Estimated about 6 months
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival)
6 secondary outcomes
Overall Survival (OS)
Time frame: From enrollment to death of patients. Estimated about 1 year
Objective Response Rate (ORR)
Time frame: From enrollment to 2 months after treatment
Disease Control Rate (DCR)
Time frame: From enrollment to 2 months after treatment
Duration of Response（DOR）
Time frame: From first documented CR or PR until disease progression or death(up to 1 year)
Quality of life (QOL)
Time frame: up to 1 year
Incidence of treatment-related adverse events
Time frame: up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2017.
- Derived from this study: PubMed 29245310Wang L, Liang L, Yang T, Qiao Y, Xia Y, Liu L, Li C, Lu P, Jiang X. A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. Medicine (Baltimore). 2017 Dec;96(49):e9053. doi: 10.1097/MD.0000000000009053.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Apatinib and Irinotecan in people with High-grade Glioma, run by The First People's Hospital of Lianyungang at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaodong Jiang, Doctor (+86018961326201, jxdysy1970@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: From enrollment to progression of disease. Estimated about 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02848794, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2017.