Pilot Study of Anlotinib With STUPP Regimen for Patients With Newly Diagnosed Glioblastoma

Pilot Study of Anlotinib in Combination With STUPP Regimen for Treatment of Patients With Newly Diagnosed Glioblastoma

The purpose of this study is to test the the efficacy and safety of Anlotinib in combination with STUPP regimen for patients with newly diagnosed glioblastoma.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Radiation: Radiotherapy was initiated 4 to 6 weeks postoperatively.; Drug: Drug is Anlotinib.; Drug: Drug is Temozolomide Capsule.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Primary, pathologically confirmed glioblastoma, and complete molecular biological marker tests (MGMT, 1p/19q, IDH, TERT, BRAF, p53, EGFR);
2. 2 ~ 6 weeks after operation; the surgical incision healed well;
3. Presence of lesions evaluable according to Rano criteria;
4. Aged 18-70 years;
5. Karnofsky performance status (KPS) ≥ 60;
6. The dose of corticosteroid therapy was stable or gradually reduced in the past 5 days;
7. No previous radiotherapy, chemotherapy, immunotherapy, or biologic therapy;
8. Serum hemoglobin ≥ 100 g/L, platelet count ≥ 80 × 109/L, neutrophil count ≥ 1.5 × 109/L;
9. Serum creatinine ≤ 1.25 × ULN or creatinine clearance ≥ 60 mL/min;
10. Serum bilirubin ≤ 1.5 × ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN, alkaline phosphatase ≤ 5 × ULN;
11. Normal coagulation function (PT prolongation does not exceed 3s, APTT prolongation does not exceed 10s);
12. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and 8 days after administration of the trial drug. Males must agree to use an appropriate method of contraception or be surgically sterile during the trial and after 8 weeks of trial drug administration;
13. Patient is sufficiently compliant with study and follow-up procedures;
14. Patients signed a formal informed consent form to indicate that they understood that the study was in accordance with hospital policy and ethical requirements.

Exclusion Criteria:

1. Secondary glioblastoma;
2. Patients with any other malignant tumor before or now, except skin non-melanotic carcinoma or cervical carcinoma in situ;
3. Any other diseases or conditions are contraindications to chemoradiotherapy (such as active phase of infection, within 6 months after cerebral myocardial infarction, symptomatic heart disease including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy);
4. Pregnant or lactating women;
5. Women and men who are likely to become pregnant but are unwilling to take appropriate contraceptive measures;
6. Evidence of hereditary bleeding constitution or coagulation disorders;
7. Patients requiring anticoagulant therapy due to other diseases;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single-arm; single-arm Drug: Anlotinib Drug: Temozolomide Radiotherapy:Radiotherapy was initiated 4 to 6 weeks postoperatively at a dose of 1.8-2.0 Grays (Gy) per fraction for 5 days per week for 6 weeks with a total dose of 54-60 Gy.

Radiation: Radiotherapy was initiated 4 to 6 weeks postoperatively.; Radiotherapy was initiated 4 to 6 weeks postoperatively at a dose of 1.8-2.0 Grays (Gy) per fraction for 5 days per week for 6 weeks with a total dose of 54-60 Gy.; Drug: Drug is Anlotinib.; Anlotinib 8 mg/day (Chia-tai Tianqing Pharmaceutical Co., Ltd.) was given orally on days 1 to 14 per 3-week cycle for 2 cycles during concomitant therapy and maximally 8 cycles during adjuvant chemotherapy. One week after discontinuation of adjuvant chemotherapy, anlotinib 8 mg/day was given for maintenance .; Drug: Drug is Temozolomide Capsule.; Temozolomide 75 mg/m2/day was taken for maximally 49 days during concurrent chemoradiotherapy. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients received adjuvant temozolomide for 5 days every 28 days, first cycle 150 mg/m2/day and subsequent cycles 200 mg/m2/day for maximally 6 cycles .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-Free Survival	from enrollment to progression or death (for any reason),assessed up to 18months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	from enrollment to death (for any reason).assessed up to 24 months
adverse event	Adverse events are described in terms of CTC AE 5.0	from enrollment to death (for any reason).assessed up to 24 months
Health-related quality of life	Health-related quality of life are measured by the EORTC-QL30/BN20.	from enrollment to death (for any reason).assessed up to 24 months
Neurocognitive function	Neurocognitive function are measured by John-Hopkins adapted cognitive exam (ACE).	from enrollment to death (for any reason).assessed up to 24 months

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Chen Ming, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): August 23, 2022

Study Registration Dates

• First Submitted: October 6, 2019
• First Submitted That Met QC Criteria: October 6, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: GBM-AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No