Phase 1-2 of Temozolomide and Hypofractionated Radiotherapy in Tx of Supratentorial Glioblastoma Multiform

Browse trials for

• Glioblastoma 1,920
• Brain Neoplasms 1,960

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.

This study's enrollment of 30 is below the median of 36 across 1,618 interventional studies indexed under Glioblastoma.

Lead sponsor

Stanford University is the lead sponsor of 2,117 studies on the registry; 425 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 197 (76%) have results posted.

Study arms

• Experimental
  Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide

  Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

  Drug: Temozolomide · Procedure: Stereotactic Radiosurgery (SRS)

• Experimental
  Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide

  Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

  Drug: Temozolomide · Procedure: Stereotactic Radiosurgery (SRS)

• Experimental
  Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide

  Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

  Drug: Temozolomide · Procedure: Stereotactic Radiosurgery (SRS)

• Experimental
  Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide

  Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

  Drug: Temozolomide · Procedure: Stereotactic Radiosurgery (SRS)

Interventions

• DrugTemozolomide

  75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.

  Also known as: Temodar, Temodal

• ProcedureStereotactic Radiosurgery (SRS)

  Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)

  Also known as: Hypofractionated stereotactic radiosurgery (h-SRS), Hypofractionated stereotactic radiotherapy, Cyberknife surgery

Primary outcomes

1. Number of Dose-limiting Toxicities (DLTs)

   The maximum-tolerated dose (MTD) of study treatment (temozolomid plus hypofractionated radiotherapy administered as 5 fractions) is defined as either: * The highest radiation dose per protocol, or * The radiation dose at which dose-limiting toxicities (DLTs) occurred in ≥ 2 of 3 participants at a dose level, and/or ≥ 2 of 6 participants, at a dose level. Dose-limiting toxicity (DLT) was defined as a treatment-related (with possible, probable or definite attribution) Grade 3 to 5 CNS toxicity \[Common Terminology Criteria for Adverse Events (CTCAE) v4\] occurring within 30 days of stereotactic radiosurgery (SRS). The non-stratified outcome is reported as the number of DLTs observed in by radiation dose and by strata (Planning Target Volume (PTV) \< 60 cm³ and from 60 to 150 cm³).

   Time frame: 30 days

Secondary outcomes

1. Number of Acute Toxicity Within 30 Days

   Acute toxicity is defined as treatment-related adverse events that occur within 30 days of receiving radiotherapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is used to grade adverse events. The non-stratified outcome is reported as number of treatment-related adverse events observed for each radiotherapy dose level. Acute toxicity is based on radiotherapy dose level not tumor volume, and is reported by radiotherapy dose level only.

   Time frame: 30 days

2. Long-term Toxicity After More Than 30 Days

   Long-term toxicity is defined as treatment-related adverse events (any grade or any Body System) that occur ≥ 30 days after receiving radiotherapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is used to grade adverse events. The non-stratified outcome is reported as number of treatment-related adverse events observed for each dose level. Long-term toxicity is based on radiotherapy dose level not tumor volume, and is reported by radiotherapy dose level only.

   Time frame: 12 months

3. Percent of Participants With Radiographic Response

   Radiographic response rate was assessed following radiotherapy until disease progression. Response is considered to be the sum and proportion participants that achieved a complete response (CR); partial response (PR); or minor response (MR). The outcome is expressed as a number without dispersion for each cohort. CR: Tumor is no longer detected by computed tomography (CT) or magnetic resonance imaging (MRI). PR: Decrease in the product of the two greatest diameters \> 50%, as determined by CT or MRI, with no new lesions, and the same or lower dose of dexamethasone. MR: Decrease in the product of the two greatest diameters \< 50%, as determined by CT or MRI, and neither PR nor PD. PD: New tumor lesion, or \> 25% increase in the product of the two greatest diameters of target lesion, as determined by CT or MRI, provided that within 2 months of completion of radiotherapy, the participant has not had a decrease in steroid dose since the last evaluation.

   Time frame: 6 months

4. Progression-free Survival

   Progression-free survival (PFS) following radiotherapy, measured in months. Progressive disease (PD) is defined as: New tumor lesion, or \> 25% increase in the product of the 2 greatest diameters of target lesion, as determined by computed tomography (CT) or magnetic resonance imaging (MRI), provided that within 2 months of completion of radiotherapy, the participant has not had a decrease in steroid dose since the last evaluation. The outcome is expressed as the median with 95% confidence interval for each cohort.

   Time frame: 18 Months.

5. Overall Survival (OS)

   Overall survival (OS) was assessed as those participants remaining alive with any tumor status following radiotherapy after 20 months. The outcome is stratified by Planning Target Volume (PTV) \< 60 cm³ or 60 to 150 cm³, and expressed as the median value with 95% confidence interval.

   Time frame: 20 Months.

6. Quality of Life by European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30) Survey

   European Organization for Research and Treatment of Cancer (EORTC-QLQ C30) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). The EORTC-QLQ C30 survey has 30 questions and responses are on scale of 1 to 4 with 1 indicating "not at all" and 4 indicating "very much". The total score can range from 30 to 120. The outcome is stratified by Planning Target Volume (PTV) \< 60 cm³ or 60 to 150 cm³, and is expressed as the mean of the difference from baseline to 12 months, with 95% confidence interval.

   Time frame: 12 Months

7. Quality of Life by Brain-20 Survey

   Brain-20 (BN-20) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). The Brain-20 (BN-20) quality of life survey has 20 questions and responses are on scale of 1 to 4 with 1 indicating "not at all" (most favorable) and 4 indicating "very much" (least favorable). The total score can range from 20 to 80, and the result is expressed as the difference from baseline (study entry) to 12 months after the start of treatment. The outcome is stratified by Planning Target Volume (PTV) \< 60 cm³ or 60 to 150 cm³, and expressed as the mean with 95% confidence interval.

   Time frame: 12 months

8. Quality of Life by MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Survey

   MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). MDASI-BT quality of life survey has 23 questions and responses are on scale of 0 to 10 with 0 indicating "did not interfere" (most favorable) and 10 indicating "interfered completely" (least favorable). A participant's overall score is computed as the mean of that participant's individual scores, and can range 0 to 10. The outcome is stratified by Planning Target Volume (PTV) \< 60 cm³ or 60 to 150 cm³, and expressed as the mean difference from baseline with 95% confidence interval. A positive value for the mean indicates worsening quality of life.

   Time frame: 12 months

9. Treatment Failure Analysis

   Treatment failure in individual participants, ie, tumor recurrence or metastasis, can be described by the location relative to the first treatment failure (ie, infield, marginal, or distal), as further defined below. Failure pattern is defined as tumor recurrence or metastasis relative to the primary lesion that is * Infield: at tumor or within 5 mm * Marginal: \> 5 mm or ≤ 20 mm from tumor * Distal: \> 20 mm from tumor The outcome will be reported as the number of participants who failed treatment for each type of failure, ie, infield, marginal, or distal failure.

   Time frame: 18 months

Baseline characteristics

Study documents

• Protocol and statistical analysis plan · Dec 3, 2015

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No