Microsurgical Resection Combined With Photodynamic Therapy for Recurrent Glioblastoma

N/AActive Not RecruitingNCT07832448

Yonggao Mou10 enrolled

Overview

This single-center, prospective, single-arm, open-label clinical study evaluates the effectiveness and safety of microsurgical resection combined with photodynamic therapy (PDT) in patients with recurrent glioblastoma (GBM). Patients receive intravenous hematoporphyrin injection (Hiporfin) 5 mg/kg 48-72 hours before surgery. Standard craniotomy with microsurgical resection of the recurrent tumor is then performed, followed by intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser (fluence 150-200 J/cm2). The primary outcome is the rate of tumor recurrence within 2 years after surgery. Participants are followed postoperatively for up to 24 months with contrast-enhanced brain MRI, neurological and quality-of-life assessments (EORTC QLQ-C30), and adverse event monitoring.

Background: For recurrent glioblastoma (WHO grade IV), no standard therapy has been established, and the median overall survival after recurrence is 24-44 weeks. Tumor-targeted photodynamic therapy (PDT) uses a photosensitizer that preferentially accumulates in tumor tissue; activation with 630-nm laser light generates reactive oxygen species that selectively kill residual tumor cells while sparing normal brain. Design: Prospective, single-arm, open-label, single-center study (Sun Yat-sen University Cancer Center, Guangzhou, China). Planned sample size: 10 participants. Treatment: Dexamethasone 10 mg intravenously once daily for 3 days before surgery. Two days before surgery, patients enter a darkened room and undergo a photosensitizer skin test (scratch test or intradermal test, 0.01 mg/mL). Patients with a negative skin test receive hematoporphyrin injection (Hiporfin, hematoporphyrin derivative, Chongqing Maile Biopharmaceutical Co., Ltd.; 5 mL: 25 mg) at 5 mg/kg diluted in 250 mL normal saline by light-protected intravenous infusion. Forty-eight hours after infusion, standard craniotomy with microsurgical resection of the recurrent tumor is performed, and the resection cavity is irradiated with a 630-nm semiconductor laser (output power 1 W; power density 120-150 mW/cm2; fluence 150-200 J/cm2; approximately 10-20 minutes) using a cylindrical diffuser or flat-cut fiber selected according to the cavity shape. After phototherapy, the wound is closed routinely. Postoperatively, patients remain in a darkened room with whole-body skin protection for 72 hours and avoid direct outdoor sunlight until 30 days after surgery. Follow-up: Contrast-enhanced brain MRI at day 3, day 7 (+/-1), day 30 (+/-2), day 90 (+/-2), day 180 (+/-2), day 270 (+/-2), and day 360 (+/-1); thereafter every 2 months (efficacy) and monthly (survival). Neurological examination, Karnofsky/ECOG performance status, EORTC QLQ-C30 quality-of-life assessment, and laboratory safety tests are performed at scheduled visits. Analysis: Efficacy and safety analyses will be performed on the per-protocol set. All statistical tests will be two-sided with P \<= 0.05 considered significant. Adverse events will be graded according to NCI CTCAE version 5.0 and coded with MedDRA.

Interventions

Hematoporphyrin Injection (Hiporfin)DRUG

Skin test (scratch or intradermal, 0.01 mg/mL) 2 days before surgery; if negative, hematoporphyrin derivative (HpD) 5 mg/kg in 250 mL normal saline by light-protected intravenous infusion 48-72 hours before surgery.

Microsurgical Tumor ResectionPROCEDURE

Standard craniotomy for microsurgical gross-total or subtotal resection of the recurrent glioblastoma, performed 48 hours after photosensitizer infusion.

630-nm Semiconductor LaserDEVICE

Intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser: output power 1 W, power density 120-150 mW/cm2, energy density 150-200 J/cm2, approximately 10-20 minutes, using cylindrical diffuser or flat-cut fiber according to cavity shape.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18-65 years, any sex * KPS score \>= 70 and ECOG performance status 0-2 * Patient and family members willing and able to provide written informed consent * Histopathologically confirmed glioblastoma (WHO grade IV) that has progressed or recurred after standard radiotherapy and chemotherapy, based on radiological evidence of measurable disease * More than 3 months since completion of brain radiotherapy * Hospitalized for recurrence/progression with a sizable lesion causing related symptoms and/or mass effect, for which gross-total or subtotal resection is considered feasible at reoperation * No concomitant malignancy, severe autoimmune disease or congenital immunodeficiency, severe active infection, cranial nerve disorder, or psychiatric disease * Life expectancy greater than 12 weeks * Cardiac function: essentially normal electrocardiogram, stable hemodynamics, left ventricular ejection fraction \> 55% * White blood cell count \> 3.5 x 10\^9/L, platelet count \> 100 x 10\^9/L, absolute neutrophil count \> 1.5 x 10\^9/L, hemoglobin \> 90 g/L * ALT and AST \< 2.5 x upper limit of normal (\< 5 x ULN if hepatic impairment mainly due to tumor infiltration), total bilirubin \< 1.5 x ULN, serum creatinine \< 1 x ULN * INR or prothrombin time \< 1.5 x ULN and APTT \< 1.5 x ULN (for patients on anticoagulation, PT/PTT within the expected therapeutic range) * Negative for HIV antibody, Treponema pallidum antibody, HBsAg, HCV antibody, and EBV-DNA * Female subjects must use effective contraception throughout the study, with negative serum or urine pregnancy test at screening and during the study * Able to attend regular follow-up visits at the study institution throughout the trial * Expected benefit of participation judged to outweigh the risks by the investigators Exclusion Criteria: * KPS score \< 70 * Prior or concurrent malignancy at other sites, unless disease-free for \>= 3 years * Pregnant or lactating women * History of allergy to photosensitizers or hematoporphyrin * Porphyria or soy allergy * Contraindications to surgery * Other uncontrolled active infection * Treatment with any investigational drug within 30 days before study entry * Psychiatric disease or other conditions (e.g., uncontrolled cardiac or pulmonary disease, diabetes) precluding compliance with study treatment and monitoring * Severe renal or hepatic impairment (bilirubin \> 1.5 x ULN, alkaline phosphatase and AST \> 2.5 x ULN, creatinine clearance \< 30 mL/min) * Prior allogeneic tissue or organ transplantation * Poor compliance or inability to follow skin photosensitivity precautions * HIV-positive or AIDS-related disease * Contraindications to magnetic resonance imaging * Follow-up impossible for psychological, family, social, or geographical reasons * Lack of legal capacity (deprived of liberty or under guardianship) * Refusal to participate or to provide consent * Any other condition judged unsuitable for enrollment by the investigator

Outcomes

Primary Outcomes

Rate of tumor recurrence or progression within 2 years after surgery

The proportion of participants with radiologically confirmed tumor recurrence or progression on contrast-enhanced brain MRI within 24 months after combined surgery and PDT, assessed according to the radiologic criteria specified in the study protocol (maximum perpendicular diameters of measurable lesions).

Time frame: 24 months after surgery (brain MRI every 2 months)

Secondary Outcomes

Recurrence-free survival (RFS)

Time from surgery to first radiologically documented recurrence or progression

Time frame: From date of surgery (Day 0) to first documented recurrence/progression or last follow-up; MRI every 2 months, up to 24 months

Overall survival (OS)

Time from surgery to death from any cause.

Time frame: From date of surgery to death from any cause or last follow-up; monthly, up to 24 months

Incidence of adverse events, including skin phototoxicity

Adverse events and serious adverse events graded with NCI CTCAE version 5.0, with specific grading of photosensitivity (skin phototoxicity) reactions occurring during the light-protection period.

Time frame: From study drug administration (Day 0) through Day 360 (+/-1) and all subsequent follow-up visits

Change in quality of life (EORTC QLQ-C30)

EORTC QLQ-C30 (V3.0) scores administered at baseline and scheduled postoperative visits; change from baseline reported.

Time frame: Baseline (preoperative) through Day 360 (+/-1) and follow-up visits