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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01120639
Recruitment Status : Active, not recruiting
First Posted : May 11, 2010
Results First Posted : July 31, 2019
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Scott Soltys, Stanford University

Tracking Information
First Submitted Date  ICMJE May 7, 2010
First Posted Date  ICMJE May 11, 2010
Results First Submitted Date  ICMJE February 7, 2019
Results First Posted Date  ICMJE July 31, 2019
Last Update Posted Date August 13, 2019
Study Start Date  ICMJE April 2010
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
Number of Dose-limiting Toxicities (DLTs) [ Time Frame: 30 days ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2010)
  • Determine the maximum tolerated dose (MTD) of hypofractionated radiotherapy given in 5 fractions with temozolomide for the treatment of glioblastoma multiforme [ Time Frame: Duration of study ]
  • Determine the progression-free survival rate. [ Time Frame: Duration of study ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2019)
  • Number of Acute Toxicity Within 30 Days [ Time Frame: 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.
  • Long-term Toxicity After More Than 30 Days [ Time Frame: 12 months ]
    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.
  • Percent of Participants With Radiographic Response [ Time Frame: 6 months ]
    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.
  • Progression-free Survival [ Time Frame: 18 Months. ]
    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.
  • Overall Survival (OS) [ Time Frame: 20 Months. ]
    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.
  • Quality of Life by European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30) Survey [ Time Frame: 12 Months ]
    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.
  • Quality of Life by Brain-20 Survey [ Time Frame: 12 months ]
    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.
  • Quality of Life by MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Survey [ Time Frame: 12 months ]
    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.
  • Treatment Failure Analysis [ Time Frame: 18 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2010)
  • Determine the short- and long-term adverse effects. [ Time Frame: Duration of study ]
  • Determine the radiographic response rate. [ Time Frame: Duration of study ]
  • Determine the overall survival rate. [ Time Frame: Duration of study ]
  • Perform patterns of failure analysis. [ Time Frame: Duration of study ]
  • Assess quality of life during treatment. [ Time Frame: Duration of study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1-2 of Temozolomide and Hypofractionated Radiotherapy in Tx of Supratentorial Glioblastoma Multiform
Official Title  ICMJE A Phase 1-2 Trial of Temozolomide and Hypofractionated Radiotherapy in Treatment of Supratentorial Glioblastoma Multiforme
Brief Summary The purpose of this study is to investigate the safety and effectiveness of a combination treatment for glioblastoma multiforme utilizing radiotherapy plus the FDA-approved chemotherapy drug temozolomide
Detailed Description

Primary Objective: To determine the maximum tolerated dose (MTD), based on acute CNS toxicity at 30 days, of hypofractionated radiotherapy given in 5 fractions with temozolomide for the treatment of glioblastoma multiforme.

Secondary Objectives:

  1. Assess the short- and long-term adverse effects.
  2. Determine the radiographic response rate.
  3. Determine the overall survival rate.
  4. Assess quality of life during treatment

To determine the maximum tolerated dose (MTD) of hypofractionated (5 fractions) radiotherapy with temozolomide for the treatment of glioblastoma multiforme, patients will be evaluated by a multi-disciplinary team composed of radiation oncologists, neurosurgeons, and neuro-oncologists to assess for their eligibility. Patient's oncologic history, presenting symptoms, physical examination, pathology, and imaging studies will be reviewed. Patients will be evaluated for surgical candidacy and resectability. Patients who are surgical candidates will undergo a surgical resection prior to radiotherapy. Patients whose tumors are unresectable or are not good surgical candidates will undergo a biopsy for tissue diagnosis. Radiation will be delivered in five fractions.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose-escalation with 2-level stratification
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Cancer of Brain and Nervous System
  • Glioblastoma Multiforme
Intervention  ICMJE
  • Drug: Temozolomide
    75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.
    Other Names:
    • Temodar
    • Temodal
  • Procedure: Stereotactic Radiosurgery (SRS)
    Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
    Other Names:
    • Hypofractionated stereotactic radiosurgery (h-SRS)
    • Hypofractionated stereotactic radiotherapy
    • Cyberknife surgery
Study Arms  ICMJE
  • 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.
    Interventions:
    • 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.
    Interventions:
    • 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.
    Interventions:
    • 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.
    Interventions:
    • Drug: Temozolomide
    • Procedure: Stereotactic Radiosurgery (SRS)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 8, 2015)
30
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2010)
24
Estimated Study Completion Date  ICMJE November 2020
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histopathologically confirmed newly diagnosed glioblastoma multiforme. Diagnosis must be made by surgical biopsy or excision
  • The tumor must be supratentorial in location
  • The planning target volume (tumor plus margin) must measure ≤ 150 cm^3 in volume
  • Age ≥ 18 years
  • Life expectancy of at least 12 weeks
  • Patient must have adequate organ function to tolerate temozolomide (details in the protocol)

Exclusion Criteria:

  • Patients who have previously been treated with brain irradiation to the region that would result in overlap of the radiation fields
  • Tumor foci detected below the tentorium
  • Multifocal disease or leptomeningeal spread
  • Prior allergic reaction to the study drugs involved in this protocol
  • Patients with pacemaker will be allowed to undergo CT instead of MRI
  • Pediatric patients (age < 18), pregnant women, and nursing patients will be excluded
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01120639
Other Study ID Numbers  ICMJE IRB-17774
SU-04202010-5726 ( Other Identifier: Stanford University )
BRN0012 ( Other Identifier: OnCore )
IRB-17774 ( Other Identifier: Stanford IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Scott Soltys, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Scott Gerard Soltys, MD Stanford University
PRS Account Stanford University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP