Glioblastoma
Conditions
Brief summary
The purpose of this study is to evaluate the safety of combination therapy of radiotherapy and temozolomide (concomitant radiotherapy phase), and then temozolomide monotherapy (monotherapy phase), in patients with newly diagnosed glioblastoma multiforme. Progression free survival and response rate will also be calculated.
Interventions
RADIATIONRadiotherapy
Radiotherapy will be administered in combination with temozolomide during the concomitant radiotherapy phase. Radiotherapy will consist of a conventionally fractioned regimen, delivering a total dose of 60 Gy in 6 weeks, in a once daily schedule of 2 Gy per fraction, for a total of 30 fractions. Radiation will be provided by a linear accelerator of x ray energy of 4 MV or higher.
DRUGTemozolomide
During the concomitant radiotherapy phase (6 weeks), temozolomide will be administered in combination with radiotherapy, once daily at 75 mg/m2/day. Then, during the monotherapy phase, subjects will receive 6 cycles of temozolomide alone. Each cycle will last 28 days, and temozolomide will be administered once daily from Day 1 to Day 5 of each cycle. The dose of temozolomide in the first cycle will be 150 mg/m2/day, and may be increased to 200 mg/m2/day for Cycle 2 and subsequent cycles depending on nonhematologic toxicity observed and neutrophil and platelet count values. Capsules containing 5 mg, 20 mg, or 100 mg of temozolomide will be combined to achieve each subject's calculated dose.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histopathologically confirmed newly diagnosed glioblastoma multiforme with WHO grade IV. * Histological diagnosis must be made locally after biopsy or neurosurgical tumor resection. * Four or more unstained tissue sections or a paraffin block must be provided to the Pathological Judgment Committee as tissue specimens. * Initial surgery/biopsy at diagnosis performed \<=6 weeks (42 days) prior to treatment with temozolomide. * Age: \>=18 and \<=70 years. * ECOG performance status \<=2. * Stable, non-increasing dose of corticosteroids over the 14 days prior to treatment with temozolomide. * No prior chemotherapy or radiotherapy. * Laboratory test values obtained within 14 days before initiation of administration of temozolomide must satisfy the following criteria: * absolute neutrophil count \>= 1500/mm\^3; * platelet count \>= 100,000/mm\^3; * serum creatinine \<=1.5 times the upper limit of laboratory normal; * total bilirubin \<=1.5 times the upper limit of laboratory normal; * glutamic oxaloacetic transaminase or glutamic pyruvic transaminase \<2.5 times the upper limit of laboratory normal; * alkaline phosphatase \< 2.5 times the upper limit of laboratory normal. * Absence of pathological conditions that interfere with taking oral drugs. * Contraception during the study period (from informed consent to the day of the last observation/examination of this study) is required in sexually active, potentially fertile patients, regardless of sex, under the supervision of the investigator or sub-investigator. * The investigator and/or subinvestigator must judge that life expectancy is 12 weeks or more. * Patients may be included regardless of sex or inpatient/outpatient.
Exclusion criteria
* Extensively disseminated glioblastoma multiforme. * Severe disorders in the heart, liver, kidney, blood, etc. * Presence of previous or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and non melanoma skin cancer. * Women who are pregnant or lactating. * Women who may be pregnant or who could become pregnant and do not adopt contraception method(s). * Participation in another clinical study within 6 weeks prior to the initiation of administration of temozolomide. * Subjects who the investigator and/or subinvestigator judged inappropriate to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events With an Incidence of Greater Than or Equal to 20% | until 30 days after the completion of administration of monotherapy | Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. Adverse events were classified under the system organ class using MedDRA-J Version 11.0. |
| Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | until 30 days after the completion of administration of monotherapy | Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. |
| Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20% | until 30 days after the completion of administration of monotherapy | Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression Free Survival (PFS) for 1 Year | 1 year after the start of admininstration in the concomitant radiotherapy phase | Administration of SCH 52365 was continued until progression was observed (progression was judged by the investigator based on MRI and clinical symptoms). |
| Number of Participants With a Response (Complete Response [CR] + Partial Response [PR]) in Terms of Overall Tumor Response | 1 year after the start of administration in the concomitant radiotherapy phase | CR = measurable lesion disappeared. PR = total sum of lesions measurable in bidimension decreased by 50% or more on whole and no secondary progression attributable to tumor was noted. No onset of new lesion. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiotherapy/Temozolomide It is the only arm of the study. Subjects receive a combination of radiotherapy and temozolomide, and then temozolomide monotherapy. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Concomitant Radiotherapy Period | Adverse Event | 2 |
| Monotherapy Period | Adverse Event | 2 |
| Monotherapy Period | Death | 1 |
| Monotherapy Period | Progression of primary disease | 11 |
Baseline characteristics
| Characteristic | Radiotherapy/Temozolomide |
|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 9.4 |
| Centralized Pathologic Diagnosis Anaplastic Astrocytoma | 1 Participants |
| Centralized Pathologic Diagnosis Glioblastoma Multiforme | 27 Participants |
| Centralized Pathologic Diagnosis Gliosarcoma | 1 Participants |
| Centralized Pathologic Diagnosis High Grade Astrocytoma | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 14 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 11 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 5 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4 | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 5 | 0 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 14 Participants |
| Type of Surgery Biopsy | 2 Participants |
| Type of Surgery Partial Extraction | 21 Participants |
| Type of Surgery Radical Extraction | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 13 / 30 |
Outcome results
Primary
Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20%
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.
Time frame: until 30 days after the completion of administration of monotherapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiotherapy/Temozolomide | Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20% | lymphocyte count decreased | 24 Participants |
| Radiotherapy/Temozolomide | Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20% | white blood cell count decreased | 14 Participants |
| Radiotherapy/Temozolomide | Abnormal Changes in Laboratory Test Values With an Incidence of Greater Than or Equal to 20% | eosinophil percentage increased | 10 Participants |
Primary
Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20%
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.
Time frame: until 30 days after the completion of administration of monotherapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | constipation | 15 Participants |
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | nausea | 11 Participants |
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | vomiting | 6 Participants |
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | neutrophil count decreased | 6 Participants |
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | weight decreased | 6 Participants |
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | anorexia | 9 Participants |
| Radiotherapy/Temozolomide | Adverse Drug Reactions With an Incidence of Greater Than or Equal to 20% | malaise | 7 Participants |
Primary
Adverse Events With an Incidence of Greater Than or Equal to 20%
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. Adverse events were classified under the system organ class using MedDRA-J Version 11.0.
Time frame: until 30 days after the completion of administration of monotherapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | alopecia | 25 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | nausea | 17 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | anorexia | 17 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | constipation | 15 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | malaise | 14 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | rash | 11 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | weight decreased | 11 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | headache | 10 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | vomiting | 9 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | dry skin | 8 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | nasopharyngitis | 8 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | diarrhea | 7 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | convulsion | 7 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | pruritus | 6 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | neutrophil count decreased | 6 Participants |
| Radiotherapy/Temozolomide | Adverse Events With an Incidence of Greater Than or Equal to 20% | wound complication | 6 Participants |
Secondary
Number of Participants With a Response (Complete Response [CR] + Partial Response [PR]) in Terms of Overall Tumor Response
CR = measurable lesion disappeared. PR = total sum of lesions measurable in bidimension decreased by 50% or more on whole and no secondary progression attributable to tumor was noted. No onset of new lesion.
Time frame: 1 year after the start of administration in the concomitant radiotherapy phase
Population: Response rate in terms of tumor response (ratio of CR + PR) in 19 participants was assessed by Efficacy and Safety Evaluation Committee. 19 participants were found to have measurable lesions. Nineteen participants (as opposed to 30 participants) were analyzed because that is how many participants were still alive 1 year after start of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiotherapy/Temozolomide | Number of Participants With a Response (Complete Response [CR] + Partial Response [PR]) in Terms of Overall Tumor Response | 6 Participants |
Secondary
Number of Participants With Progression Free Survival (PFS) for 1 Year
Administration of SCH 52365 was continued until progression was observed (progression was judged by the investigator based on MRI and clinical symptoms).
Time frame: 1 year after the start of admininstration in the concomitant radiotherapy phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiotherapy/Temozolomide | Number of Participants With Progression Free Survival (PFS) for 1 Year | 11 Participants |