MGMT-Unmethylated GlioblastomaPhase 2NCT05033587
Study of AK105 With Anlotinib and Radiotherapy Adjuvant Therapy in MGMT Unmethylated Newly Diagnosed Glioblastoma.
A Phase 2 study testing Anlotinib, AK105 and Radiotherapy in people with MGMT-Unmethylated Glioblastoma, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
Trial summary
This is a prospective, open-label single-arm, exploratory, two-stage design trial, aiming to investigate safety and efficacy of AK105 with anlotinib and radiotherapy adjuvant therapy in MGMT unmethylated newly diagnosed glioblastoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- MGMT-Unmethylated Glioblastoma
- What is being tested?
- Anlotinib, AK105 and Radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- Sep 2021to 1 Nov 2023
- Phase
- Phase 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient voluntarily joined the study and signed a written informed consent;
- Pathologically confirmed treatment-naïve glioblastoma with PCR tested MGMT unmethylated;
- The interval between the last biopsy or surgery is 4-6 weeks, and the surgical incision is healed well;
- According to Rano criteria, there are evaluable measurable disease;
- 18-70 years of age;
- Karnofsky performance status (KPS) ≥ 60; and estimated survival of at least 3 months;
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- The main organ function to meet the following criteria:
- 1) routine blood test: HB≥90g/L(no blood transfusion in 14 days); ANC≥1.5×109/L; White blood cell counts≥3.5×109/L; PLT≥90×109/L; 2) blood biochemical test: ALT and AST ≤2.5×ULN(times the upper limit of normal) and if liver/bone metastases≤5×ULN; TBIL ≤1.5 ULN; Serum Cr≤1.5×ULN and CrCL≥60 ml/min; 3) APTT, INR and PT≤1.5×ULN;
- The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 6 months after it; who are not in the lactation period and examined as negative in blood serum test or urine pregnancy test within 7 days before the research.
Who cannot join
- Prior therapy with anti-angiogenic drugs, such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, surufatinib, regorafenib or fruquintinib ect, or with anti-PD-1(L1) or anti-CTLA-4 agents;
- Patients who get other monoclonal antibodies have severe hypersensitivity;
- Present or along with other malignancies within 5 years. Exceptions include cured basal cell carcinoma of the skin or in situ prostate cancer or in situ cervical cancer;
- Patients have any active autoimmune disease that required systemic treatment, including but not limited to autoimmune hepatitis, enteritis, vasculitis, nephritis; asthma that require bronchodilators for medical intervention. Exceptions include patients with vitiligo, psoriasis, alopecia or well-controlled type 1 diabetes but not required systemic treatment, or hypothyroidism with normal thyroid function after alternative treatment;
- In the past, there is a treatment toxicity of CTCAE5.0 ≥2 grade that has not been completely relieved (the adverse reaction grades in this article, unless otherwise specified, are defaulted to the CTCAE 5.0 standard);
- Immunodeficiency diagnosis or receiving chronic systemic steroid therapy (>10mg/day prednisone or equivalent) or any other form of immunosuppressive therapy, and continued to be used within 2 weeks before the first dose in this study;
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- Those with multiple factors affecting oral drugs (such as inability to swallow, post gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.);
- Imaging (CT or MRI) shows that the tumor has invaded or unclearly separated the large blood vessels;
- Patients with active bleeding, or unexplained persistent decline in hemoglobin should postpone their screening/enrollment until the bleeding stops and the investigator judges it to be safe;
- Within 4 weeks before the first dose in this study, patients with CTCAE5.0 grade 3+ bleeding; patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; on the premise that the international normalized ratio of prothrombin time (INR) ≤1.5, it is allowed to use low-dose warfarin (≤1mg/D), low-dose heparin (≤12000U /D) or low-dose aspirin (≤100mg/D) for preventive purposes;
- Within 4 weeks before the first dose in this study, patients with unhealed wounds, fractures, gastric and duodenal active ulcers, ulcerative colitis, or unresected tumors have active bleeding, or may be caused as determined by the researchers other conditions of gastrointestinal bleeding and perforation, have undergone major surgery (excluding vascular access surgery), inoculated with preventive vaccine or attenuated vaccine;
- Received the treatment of proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions within 2 weeks before the start of the study treatment(Including compound cantharidin capsules, Kangai injection, Kanglaite capsule/injection, Aidi injection, brucea javanica oil injection/capsule, Xiaoaiping tablet/injection, Huachansu capsule, etc.); or received drugs with immunomodulatory effects (including thymosin, interferon, and interleukin, except for local use to control pleural effusion or ascites);
- History of organ or blood transplantation;
- Patients have active diverticulitis, abdominal abscess, gastrointestinal obstruction;
- Patients with any severe and/or uncontrollable disease, including:
- 1) Patients with unsatisfactory blood pressure control (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg); 2)Within 6 months of the first administration patients with myocardial ischemia or myocardial infarction, arrhythmia that require treatment (including QTC ≥480ms), and grade ≥2 congestive heart failure; 3) active or uncontrolled serious infection (≥CTCAE5.0 Grade 2 infection), tuberculosis patients; 4) Known clinical history of liver disease, including viral hepatitis, carriers of hepatitis b virus must be excluded from active HBV infection, i.e., HBV DNA positive (>2500 copy /mL or >500IU/mL);known hepatitis c virus infection (HCV) and HCV RNA positive (>1 x 10^3 copy /mL), or other decompensated liver disease, chronic hepatitis requires antiviral treatment; 5) HIV test positive or Syphilis Testing RPR positive; 6) Diabetes is poorly controlled (fasting blood glucose (FBG) ≥10mmol/L); 7) Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantification is more than 1.0 g;
- Those considered by the researcher to be unsuitable for inclusion.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
Mi Yang, Dr., +86-25-83106666, yangmi@nju.edu.cn
About this study
Official title: AK105 With Anlotinib and Radiotherapy Adjuvant Therapy in MGMT Unmethylated Newly Diagnosed Glioblastoma: a Prospective, Open-label Single-arm, Exploratory Trial.
This is a prospective, open-label single-arm, exploratory, two-stage design trial, aiming to investigate safety and efficacy of AK105 with anlotinib and radiotherapy adjuvant therapy in MGMT unmethylated newly diagnosed glioblastoma.
Read the detailed description
Glioblastoma is the most common and aggressive primary brain tumor in adults. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The Central Brain Tumor Registry of the United States (CBTRUS) Statistical Report primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016, glioblastoma accounted for 48.3% of primary malignant brain tumors.
The Stupp protocol has become standard of care for the treatment of newly diagnosed GBM, however, some MGMT unmethylated glioblastomas are still resistant to temozolomide.
Immunotherapy is being studied as treatment for the cancer, AK105 is a humanized monoclonal antibody that specially binds to PD-1. Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor. Based on the mechanism study, tumor vascular abnormalities promote tissue hypoxia and increase lactic acid, thereby activating immunosuppression and inhibiting T cell function. Anti-angiogenic drugs enhance the infiltration of effector immune cells by inducing normalization of blood vessels and reducing immunosuppression.
- Conditions
- MGMT-Unmethylated Glioblastoma
- Being tested
- Anlotinib, AK105, Radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Also called Anlotinib Hydrochloride Capsules
Anlotinib a multi-target receptor tyrosine kinase inhibitor.
AK105Drug
Also called Penpulimab Injection
AK105 is a humanized monoclonal antibody that specifically binds to PD-1.
RadiotherapyRadiation
The radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy.
| Study group | Role | What they receive |
|---|---|---|
| AK105 injection with anlotinib and radiotherapy | Experimental | AK105 200mg intravenously (IV) on day 1 of each 21-day cycle until disease progression or treatment intolerance, the dose can not be adjusted.
Anlotinib 12mg capsules given orally on once daily in 21-day cycle until disease progression or treatment intolerance(14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21), the dose can be adjusted to 10mg or 8mg according to the specific conditions of the patient.
The conventional radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy. Receives: Drug: Anlotinib; Drug: AK105; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFSR-6m
Progression-Free Survival rate at 6 months.
Measured: up to 6 months
Secondary outcomes (5)
Progression-Free Survival（PFS）
PFS is defined as the time from randomization until the first documented progressive disease (PD) or death from any cause response assessment, based on Response Assessment in Neuro-Oncology (RANO) prior.
Measured: up to approximately 24 months
Objective Response Rate（ORR）
ORR is defined as percentage of subjects confirmed complete response (CR) or partial response (PR), based on Response Assessment in Neuro-Oncology (RANO) prior to progression or any further therapy.
Measured: up to approximately 24 months
Overall Survival（OS）
From the start of treatment to the date of death or the last follow-up.
Measured: up to approximately 24 months
Disease Control Rate（DCR）
The DCR is defined as the proportion of subjects with CR, PR, or stable disease (SD), based on Response Assessment in Neuro-Oncology (RANO) prior.
Measured: up to approximately 24 months
Safety
Observe any adverse events that occurred in all subjects during the clinical study and within 1 month after stopping the drug, including clinical symptoms, abnormal vital signs, and abnormalities in laboratory examinations, and record their clinical features, severity, and time of occurrence, duration, treatment methods and prognostic outcome, and determine its correlation with the study drug, based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the safety.
Measured: up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study startSep 2021 (estimated)
- Primary completion1 May 2023 (estimated)
- Study completion1 Nov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MGMT-Unmethylated GlioblastomaStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Responsible party
- Principal investigator, Yang Yang, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05033587
- Sponsor's protocol ID
- 2021-252-02
- Status last verified
- Aug 2021
- First submitted
- 27 Aug 2021
- Last updated
- 5 Sep 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AK105 With Anlotinib and Radiotherapy Adjuvant Therapy in MGMT Unmethylated Newly Diagnosed Glioblastoma: a Prospective, Open-label Single-arm, Exploratory Trial.
- ClinicalTrials.gov ID
- NCT05033587
- Acronym / sponsor ID
- 2021-252-02
- Conditions
- MGMT-Unmethylated Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Study start
- Sep 2021 (estimated)
- Primary completion
- 1 May 2023 (estimated)
- Study completion
- 1 Nov 2023 (estimated)
- First posted
- 5 Sep 2021 (actual)
- 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.
This is a prospective, open-label single-arm, exploratory, two-stage design trial, aiming to investigate safety and efficacy of AK105 with anlotinib and radiotherapy adjuvant therapy in MGMT unmethylated newly diagnosed glioblastoma.
Detailed description
Glioblastoma is the most common and aggressive primary brain tumor in adults. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The Central Brain Tumor Registry of the United States (CBTRUS) Statistical Report primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016, glioblastoma accounted for 48.3% of primary malignant brain tumors.
The Stupp protocol has become standard of care for the treatment of newly diagnosed GBM, however, some MGMT unmethylated glioblastomas are still resistant to temozolomide.
Immunotherapy is being studied as treatment for the cancer, AK105 is a humanized monoclonal antibody that specially binds to PD-1. Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor. Based on the mechanism study, tumor vascular abnormalities promote tissue hypoxia and increase lactic acid, thereby activating immunosuppression and inhibiting T cell function. Anti-angiogenic drugs enhance the infiltration of effector immune cells by inducing normalization of blood vessels and reducing immunosuppression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK105 injection with anlotinib and radiotherapy | Experimental | Drug: Anlotinib, Drug: AK105, Radiation: RadiotherapyAK105 200mg intravenously (IV) on day 1 of each 21-day cycle until disease progression or treatment intolerance, the dose can not be adjusted. Anlotinib 12mg capsules given orally on once daily in 21-day cycle until disease progression or treatment intolerance(14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21), the dose can be adjusted to 10mg or 8mg according to the specific conditions of the patient. The conventional radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- The patient voluntarily joined the study and signed a written informed consent;
- Pathologically confirmed treatment-naïve glioblastoma with PCR tested MGMT unmethylated;
- The interval between the last biopsy or surgery is 4-6 weeks, and the surgical incision is healed well;
- According to Rano criteria, there are evaluable measurable disease;
- 18-70 years of age;
Key exclusion criteria (17 listed)
- Prior therapy with anti-angiogenic drugs, such as anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, surufatinib, regorafenib or fruquintinib ect, or with anti-PD-1(L1) or anti-CTLA-4 agents;
- Patients who get other monoclonal antibodies have severe hypersensitivity;
- Present or along with other malignancies within 5 years. Exceptions include cured basal cell carcinoma of the skin or in situ prostate cancer or in situ cervical cancer;
- Patients have any active autoimmune disease that required systemic treatment, including but not limited to autoimmune hepatitis, enteritis, vasculitis, nephritis; asthma that require bronchodilators for medical intervention. Exceptions include patients with vitiligo, psoriasis, alopecia or well-controlled type 1 diabetes but not required systemic treatment, or hypothyroidism with normal thyroid function after alternative treatment;
- In the past, there is a treatment toxicity of CTCAE5.0 ≥2 grade that has not been completely relieved (the adverse reaction grades in this article, unless otherwise specified, are defaulted to the CTCAE 5.0 standard);
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 |
|---|---|---|
| AnlotinibAlso: Anlotinib Hydrochloride CapsulesAnlotinib a multi-target receptor tyrosine kinase inhibitor. | Drug | AK105 injection with anlotinib and radiotherapy |
| AK105Also: Penpulimab InjectionAK105 is a humanized monoclonal antibody that specifically binds to PD-1. | Drug | AK105 injection with anlotinib and radiotherapy |
| RadiotherapyThe radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy. | Radiation | AK105 injection with anlotinib and radiotherapy |
Primary outcome
PFSR-6m
Time frame: up to 6 months
Progression-Free Survival rate at 6 months.
5 secondary outcomes
Progression-Free Survival（PFS）
Time frame: up to approximately 24 months
Objective Response Rate（ORR）
Time frame: up to approximately 24 months
Overall Survival（OS）
Time frame: up to approximately 24 months
Disease Control Rate（DCR）
Time frame: up to approximately 24 months
Safety
Time frame: up to approximately 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
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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 2 study testing Anlotinib, AK105 and Radiotherapy in people with MGMT-Unmethylated Glioblastoma, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School 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 9 inclusion and 17 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 5 Sep 2021. 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 phase mean?
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 Mi Yang, Dr. (+86-25-83106666, yangmi@nju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFSR-6m (time frame: up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Sep 2021.