RRx-001 + Radiation + Temozolomide In Newly Diagnosed Glioblastoma and Anaplastic Gliomas (G-FORCE-1)
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|ClinicalTrials.gov Identifier: NCT02871843|
Recruitment Status : Active, not recruiting
First Posted : August 18, 2016
Last Update Posted : July 23, 2020
This is a two-part Phase I add-on clinical trial in newly diagnosed glioblastoma or GBM. By "add-on" what is meant is that the experimental intravenous therapy, RRx-001, is combined or "added on" to standard of care. In newly diagnosed GBM standard of care consists of radiotherapy + temozolomide (TMZ) for 6 weeks followed (after a 4-6 weeks break) by maintenance TMZ given until the tumor progresses or worsens. By "maintenance" therapy what is meant is that TMZ is given less frequently to prolong or extend the time during which the tumor remains stable.
G-FORCE-1 will be conducted in two parts; in the first part of the study (Dose Escalation, Part A) patients will be entered or assigned sequentially (that is consecutively) to gradually escalating or increasing doses of RRx-001 after patients have been entered on the previous dose until such time as it is no longer tolerated. At each dose level, a separate cohort or small group of at least 3 evaluable patients will be treated. RRx-001 will be administered by intravenous infusion (in other words, by slow injection in the veins) over 30-45 minutes once weekly during radiotherapy for 6 weeks followed by the FDA-approved chemotherapy, temozolomide (TMZ) alone for up to 6 months or longer.
In the second part of this study (Part B), new groups or cohorts of patients will receive RRx-001 at the dose established in Part A by intravenous infusion over 30-45 minutes once weekly during radiotherapy for 6 weeks. Then, after a 4-6 weeks break, each cohort will receive increasing doses of RRx-001 and temozolomide (in other words, a double dose escalation) to establish an acceptable safety and activity window, in other words, a dose range that is relatively free of toxicity as well as active against the tumor, although the primary purpose of this study is to assess or evaluate safety.
The reason or rationale to "add on" RRx-001 to radiotherapy and TMZ, which is described in more detail below on this page, is as follows: RRx-001 is a radiosensitizer and a chemosensitizer, which means that experimentally it increases the activity of radiation and chemotherapy in tumors. In addition, in other ongoing clinical trials, patients have experienced minimal toxicity or side effects with RRx-001 alone and also in combination with radiation in the brain; therefore, the hope is that RRx-001 will synergize or combine well with radiotherapy and TMZ in GBM without adding toxicity
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Oligodendroglioma Anaplastic Oligodendroglioma||Drug: RRx-001 dose escalation with TMZ + RT Radiation: Radiation Drug: Fixed dose Temozolomide (75 mg/m2) Drug: TMZ Maintenance||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||3+3 Dose Escalation|
|Masking:||None (Open Label)|
|Official Title:||G-FORCE-1: An Open-Label Phase 1 Two Part Dose Escalation Trial of RRx-001 Concurrent With Radiation and Temozolomide and RRx-001 + Temozolomide Post-RT In Newly Diagnosed Glioblastoma and Anaplastic Gliomas With Intact 1p/19q Chromosomes|
|Actual Study Start Date :||February 14, 2017|
|Actual Primary Completion Date :||October 11, 2019|
|Estimated Study Completion Date :||December 2020|
Experimental: Escalation of RRx-001 with TMZ + RT
Dose escalation of RRx-001 with fixed doses of Temozolomide and radiation followed by Temozolomide maintenance therapy
Drug: RRx-001 dose escalation with TMZ + RT
Dose escalation of RRx-001. Dose levels of 0.5, 1.0, 2.0 and 4.0 mg, once weekly.
Conformal or intensity-modulated radiotherapy (60 Gy in 2 Gy fractions) given 5 days a week for 30 fractions (about 6 weeks)
Drug: Fixed dose Temozolomide (75 mg/m2)
Oral temozolomide 75 mg/m2 daily for 6 weeks
Other Name: TMZ
Drug: TMZ Maintenance
TMZ maintenance at 150-200 mg/m2
- Number, frequency and type of adverse events [ Time Frame: 12 weeks ]
- Objective Response Rate (ORR) [ Time Frame: 4 months ]Objective Response rate as determined by the patient's best tumor response, Duration Of Response (DOR) and Time To Progression (TTP) using modified RANO criteria
- Clinical Benefit Rate (CBR) [ Time Frame: 4 months ]Clinical Benefit Rate as determined by the patient's best tumor response, Duration Of Response (DOR) and Time To Progression (TTP) using modified RANO criteria
- Intracranial Progression Free Survival [ Time Frame: 4 months ]Intracranial PFS is defined as the time that a patient lives with intracranial tumors before progression. Changes in intracranial tumors will be measured by MRI and scored using RANO criteria. The response assessment will take into account MacDonald Criteria using bi-dimensional measurements of the largest contrast- enhancing area, RANO Criteria, FLAIR imaging and clinical status.
- Overall Survival [ Time Frame: 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02871843
|United States, California|
|University of California San Francisco (UCSF)|
|San Francisco, California, United States, 94143|
|United States, New Jersey|
|The Cancer Institute of New Jersey (Rutgers University)|
|New Brunswick, New Jersey, United States, 08903|
|United States, New York|
|Weill Cornell Brain Tumor Center|
|New York, New York, United States, 10021|
|Study Director:||Bryan Oronsky||Chief Medical Officer|