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Phase II/III Trial of CCRT With or Without JP001 for Newly Diagnosed GBM

Primary Purpose

Glioblastoma

Status

Recruiting

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

CCRT

Temozolomide

Siroquine

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with histologically proven newly diagnosed case of GBM (WHO grade IV) and treatment-naive (chemotherapy and radiotherapy) for GBM. Diagnosis must be made by stereotactic biopsy or surgical excision, either partial or complete within 3 months prior to Visit 1.
Subject's RPA class is class III, IV or V.
Subjects with stereotactic biopsy or brain surgery must be suited for or will be scheduled for CCRT followed by Temozolomide treatment, the standard treatment recommended by institutes and fulfilled the reimbursement guideline of National Health Insurance Administration.
Subjects must have recovered from the effects of surgery, post-operative infection, and other complications prior to Visit 1. Study treatment must be performed > 3 weeks and ≤ 8 weeks after craniotomy. Ventricular fluid reservoir or Ventriculo-Peritoneal shunting tube is allowed to keep.
A diagnostic contrast-enhanced MRI of the brain must be performed postoperatively within 28 days prior to Visit 2 (Day 1).
ECOG performance status ≤ 3 at Visit 1.
Age from 20 to 80 years old at Visit 1.
Life expectation ≥ 12 weeks at Visit 1.
CBC/differential obtained at Visit 1, with adequate bone marrow function defined as follows:
1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5 x 109/L) or white blood cell (WBC) ≥ 3,000 cells/mm3 (3 x 109/L).
2. Platelets count ≥ 100,000 cells/mm3 (100 x 109/L).
3. Hemoglobin (Hgb or Hb) ≥ 10.0 g/dL (100 g/L) (Note: The use of transfusion or other intervention to achieve Hemoglobin ≥ 10.0 g/dL (100 g/L) is acceptable).
Adequate renal function, as defined below:
a. Creatinine ≤ 1.5 times upper laboratory limit at Visit 1.
Adequate hepatic function, as defined below:
1. Total Bilirubin ≤ 2.0 mg/dL (34.20 umol/L) at Visit 1.
2. ALT ≤ 3 times upper laboratory limit at Visit 1.
3. AST ≤ 3 times upper laboratory limit at Visit 1.
Subjects is able to understand and willing to comply with the study procedures and has signed the informed consent form (ICF).

Exclusion Criteria:

Other invasive malignancy. However, subject with other invasive malignancy that have been disease-free more than or equal to 10 years and deemed no need for anti-cancer treatments can be recruited. Subjects with noninvasive malignancy, including carcinoma in situ of the breast, non-melanomatous skin cancer and cervix carcinoma in situ can be recruited if disease-free and treatment free more than or equal to 3 years.
Metastases detected beyond the cranial vault.
Subjects with the following history:
1. Brain irradiation or Temozolomide usage.
2. Macular degeneration or retinopathy.
3. Renal transplantation.
Subjects are currently receiving any anti-rejection medicine or Hydroxychloroquine sulfate for rheumatoid arthritis.
Subjects with severe and active co-morbidity, defined as follows:
1. Clinical active kidney, liver, lung or cardiac disease.
2. Acute bacterial or fungal infection requiring intravenous antibiotics at Visit 1 and acquired immune deficiency syndrome (AIDS).
3. Any active infection or uncontrolled infection at Visit 1.
4. Abnormal CXR finding with risks of infection and interstitial lung disease/pneumonitis.
Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant from study drug.
Mean QTc > 500 msec (with Bazett's correction), history of familial long QT syndrome or other significant ECG abnormality noted at Visit 1.
Known hypersensitivity reactions to Temozolomide, dacarbazine (DTIC), hydroxychloroquine, 4-aminoquinoline, rapamune, sirolimus, rapamycin, or their analogs.
Women of child-bearing potential or men who are able to father a child unwilling to use a. medically acceptable method of contraception during the trial.
Subjects participated in another investigational agent study in the past 30 days or are planning to do so during the study period.
Subjects are considered ineligible for the study as judged by the investigator.
Subjects with positive HBsAg or positive anti-HCV.

Sites / Locations

Taipei Veterans General HospitalRecruiting
Tri-Service General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Radiation,Temozolomide

Radiation,Temozolomide,Siroquine(JP001)

Arm Description

CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks). Rest Phase: Rest for 4 weeks. Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles. Maintenance Phase: No maintenance treatment until disease progression confirmed.

CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks) + Daily JP001 (2 tablets once a day for 6 weeks). Rest Phase: Daily JP001(2 tablets/day) for 4 weeks. Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles + Daily JP001(2 tablets once a day) for 24 weeks (4 weeks for each cycle). Maintenance Phase: JP001(2 tablets once a day) until disease progression confirmed.

Outcomes

Primary Outcome Measures

Overall survival time.

All subjects will be followed until study end (the date of last subject last visit; the last subject need to be followed at least 30 months) or death, whichever comes first; OS defined as the time from the date of Randomization to the date of death or last follow-up.

Secondary Outcome Measures

Progression-free survival time

All subjects will be followed until study end or disease progression confirmed, whichever comes first; PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.

OS rate at 1 year.

OS defined as the time from the date of Randomization to the date of death or last follow-up.

PFS rate at 1 year.

PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.

The time and rate of OS in different RPA class.

The time and rate of PFS in different RPA class.

Objective response rate.

Defined as the proportion of subjects who were confirmed completed response or partial response determined by RANO criteria.

Changes in score of EORTC QLQ-C30

Changes in score of EORTC QLQ-BN20.

Changes in grade of ECOG performance status.

Full Information

NCT ID

NCT03008148

First Posted

December 23, 2016

Last Updated

May 10, 2021

Sponsor

Johnpro Biotech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03008148

Brief Title

Phase II/III Trial of CCRT With or Without JP001 for Newly Diagnosed GBM

Official Title

Randomized Phase II/III Trial of Radiotherapy Plus Concomitant and Adjuvant Temozolomide With or Without Hydroxychloroquine, Rapamycin for Newly Diagnosed Glioblastoma

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Recruiting

Study Start Date

October 11, 2018 (Actual)

Primary Completion Date

April 2025 (Anticipated)

Study Completion Date

April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johnpro Biotech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a multi-center, phase II/III, open-label, randomized, parallel and standard chemoradiation-controlled study where eligible subjects will be randomized at 1:1 ratio to receive control treatment or study treatment. The primary objective of this trial is to evaluate the effect of add-on JP001 to standard chemoradiation in increasing overall survival (OS) on newly diagnosed glioblastoma (GBM) patients.

Detailed Description

After enrollment, subjects' previous tumor block used for glioblastoma diagnosis that is consented to provide during the study period will be sent to a central laboratory for the assessment of MGMT status. Moreover, subjects will be randomized in either Control or Study arm at Visit 2. Subjects in Control arm will receive a standard chemoradiation. However, subjects in Study arm will receive a standard chemoradiation in combination with concurrent JP001 in whole study period. During the study, a sufficient amount of investigational products will be supplied to subjects in study groups until next scheduled visits. Subjects will self-administer investigational product orally with water at approximately the same time in each day. Subjects should fast for a minimum of 2 hours prior to any doses of JP001 and/or Temozolomide and then fast for another 1 hour after taking JP001 and/or Temozolomide. During and at the end of treatment, subjects will be evaluated for efficacy and safety parameters. Moreover, there will be a Follow-up visit for safety 4 weeks after the End-of-Treatment visit. If a subject is early withdrawn from the study, the End-of-Treatment visit should be arranged and all assessments assigned in this visit should be performed. The Safety Follow-up visit for early withdrawn subjects could be either clinic visit or telephone contact. If withdrawn subjects refuse to perform Follow-up visit, the Follow-up visit is allowed to cancel. For subjects who completed or discontinued study treatment, assessment of survival status will be performed every 8 weeks by telephone contact until death, study end (last subject last visit; the last subject needs to be followed at least 30 months), or study termination by Sponsor. Survival information will be recorded in the medical source and CRF. If subjects are lost to follow-up or refuse to receive the assessment of survival status, the investigator will record the last date subjects known to be alive in the medical source and case report form.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

288 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Radiation,Temozolomide

Arm Type

Active Comparator

Arm Description

Arm Title

Radiation,Temozolomide,Siroquine(JP001)

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

CCRT

Intervention Description

CCRT Phase: Radiation(60 Gy in 2 Gy/fx) + daily Temozolomide (75 mg/m²/day for 6 weeks).

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

Chemotherapy

Intervention Description

Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles.

Intervention Type

Drug

Intervention Name(s)

Siroquine

Other Intervention Name(s)

JP001

Intervention Description

Chemotherapy Phase: Temozolomide 150-200 mg/m² Day 1-5 of 28-Day for a maximum of 6 cycles + Daily JP001(2 tablets once a day) for 24 weeks (4 weeks for each cycle). Maintenance Phase: JP001(2 tablets once a day) until disease progression confirmed.

Primary Outcome Measure Information:

Title

Overall survival time.

Description

Time Frame

120 weeks

Secondary Outcome Measure Information:

Title

Progression-free survival time

Description

Time Frame

120 weeks

Title

OS rate at 1 year.

Description

OS defined as the time from the date of Randomization to the date of death or last follow-up.

Time Frame

1 year

Title

PFS rate at 1 year.

Description

PFS defined as the time from the date of Randomization to the date of disease progression, death or last follow-up.

Time Frame

1 year

Title

The time and rate of OS in different RPA class.

Time Frame

120 weeks

Title

The time and rate of PFS in different RPA class.

Time Frame

120 weeks

Title

Objective response rate.

Description

Defined as the proportion of subjects who were confirmed completed response or partial response determined by RANO criteria.

Time Frame

120 weeks

Title

Changes in score of EORTC QLQ-C30

Time Frame

120 weeks

Title

Changes in score of EORTC QLQ-BN20.

Time Frame

120 weeks

Title

Changes in grade of ECOG performance status.

Time Frame

120 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with histologically proven newly diagnosed case of GBM (WHO grade IV) and treatment-naive (chemotherapy and radiotherapy) for GBM. Diagnosis must be made by stereotactic biopsy or surgical excision, either partial or complete within 3 months prior to Visit 1. Subject's RPA class is class III, IV or V. Subjects with stereotactic biopsy or brain surgery must be suited for or will be scheduled for CCRT followed by Temozolomide treatment, the standard treatment recommended by institutes and fulfilled the reimbursement guideline of National Health Insurance Administration. Subjects must have recovered from the effects of surgery, post-operative infection, and other complications prior to Visit 1. Study treatment must be performed > 3 weeks and ≤ 8 weeks after craniotomy. Ventricular fluid reservoir or Ventriculo-Peritoneal shunting tube is allowed to keep. A diagnostic contrast-enhanced MRI of the brain must be performed postoperatively within 28 days prior to Visit 2 (Day 1). ECOG performance status ≤ 3 at Visit 1. Age from 20 to 80 years old at Visit 1. Life expectation ≥ 12 weeks at Visit 1. CBC/differential obtained at Visit 1, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5 x 109/L) or white blood cell (WBC) ≥ 3,000 cells/mm3 (3 x 109/L). Platelets count ≥ 100,000 cells/mm3 (100 x 109/L). Hemoglobin (Hgb or Hb) ≥ 10.0 g/dL (100 g/L) (Note: The use of transfusion or other intervention to achieve Hemoglobin ≥ 10.0 g/dL (100 g/L) is acceptable). Adequate renal function, as defined below: a. Creatinine ≤ 1.5 times upper laboratory limit at Visit 1. Adequate hepatic function, as defined below: Total Bilirubin ≤ 2.0 mg/dL (34.20 umol/L) at Visit 1. ALT ≤ 3 times upper laboratory limit at Visit 1. AST ≤ 3 times upper laboratory limit at Visit 1. Subjects is able to understand and willing to comply with the study procedures and has signed the informed consent form (ICF). Exclusion Criteria: Other invasive malignancy. However, subject with other invasive malignancy that have been disease-free more than or equal to 10 years and deemed no need for anti-cancer treatments can be recruited. Subjects with noninvasive malignancy, including carcinoma in situ of the breast, non-melanomatous skin cancer and cervix carcinoma in situ can be recruited if disease-free and treatment free more than or equal to 3 years. Metastases detected beyond the cranial vault. Subjects with the following history: Brain irradiation or Temozolomide usage. Macular degeneration or retinopathy. Renal transplantation. Subjects are currently receiving any anti-rejection medicine or Hydroxychloroquine sulfate for rheumatoid arthritis. Subjects with severe and active co-morbidity, defined as follows: Clinical active kidney, liver, lung or cardiac disease. Acute bacterial or fungal infection requiring intravenous antibiotics at Visit 1 and acquired immune deficiency syndrome (AIDS). Any active infection or uncontrolled infection at Visit 1. Abnormal CXR finding with risks of infection and interstitial lung disease/pneumonitis. Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant from study drug. Mean QTc > 500 msec (with Bazett's correction), history of familial long QT syndrome or other significant ECG abnormality noted at Visit 1. Known hypersensitivity reactions to Temozolomide, dacarbazine (DTIC), hydroxychloroquine, 4-aminoquinoline, rapamune, sirolimus, rapamycin, or their analogs. Women of child-bearing potential or men who are able to father a child unwilling to use a. medically acceptable method of contraception during the trial. Subjects participated in another investigational agent study in the past 30 days or are planning to do so during the study period. Subjects are considered ineligible for the study as judged by the investigator. Subjects with positive HBsAg or positive anti-HCV.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kwan-Hwa Chi

Phone

886-2-28332211

Ext

2274

M006565@ms.skh.org.tw

First Name & Middle Initial & Last Name or Official Title & Degree

Susan Huang

Phone

886-2-28332211

Ext

2612

susan.huang@johnpro.com.tw

Facility Information:

Facility Name

Taipei Veterans General Hospital

City

Taipei City

ZIP/Postal Code

11217

Country

Taiwan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yu-Ming Liu

Facility Name

Tri-Service General Hospital

City

Taipei City

ZIP/Postal Code

11490

Country

Taiwan

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hsin-I Ma

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Phase II/III Trial of CCRT With or Without JP001 for Newly Diagnosed GBM

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