Clinical Trial: Phase 1 Two Part Dose Escalation Trial of RRx-001 + Radiation + Temozolomide and RRx-001 + Temozolomide Post-RT In Newly Diagnosed Glioblastoma and Anaplastic Gliomas

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

Brief Summary:

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 a

Detailed Summary:

Glioblastoma multiforme also known by the feared three letter acronym or abbreviation, GBM, is the most common, aggressive and deadly type of brain tumor, which is standardly treated with a combination of radiation and temozolomide (TMZ), an FDA approved chemotherapy agent, followed by temozolomide alone. One of the reasons why glioblastoma is so aggressive and deadly has to do with poor blood flow: it turns out that GBM has multiple inefficient and leaky blood vessels, which leads to ineffective and irregular delivery of nutrients and oxygen to the tumor.

As illogical as it may sound at first, depriving cancer cells of the oxygen and vital nutrients that they need to grow actually makes them more (not less as might be expected) aggressive and harder to treat.

Here's why: for radiation to have an effect on the tumor oxygen is required since the combination of oxygen and radiation produces unstable and highly reactive free radicals; these microscopic free radicals are the equivalent of a spray of bullets, which ricochet or bounce around violently inside the tumor producing catastrophic damage.

Likewise, for chemotherapy such as TMZ to work it has to reach the tumor and when blood vessels are so abnormal that the blood practically ceases to flow the TMZ, for example, may either never actually get there or may arrive in such small quantities that it is ineffective.

The expression "survival of the fittest" also applies: under the poorly oxygenated harsh conditions, which result from this sluggish blood flow only the toughest and most resistant cancer cells survive, making the tumor that much harder to eliminate with traditional therapies.

Think of the blood flow to the
Sponsor: EpicentRx, Inc.

Current Primary Outcome: Number, frequency and type of adverse events [ Time Frame: 12 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: EpicentRx, Inc.

Dates:
Date Received: August 11, 2016
Date Started: August 2016
Date Completion: August 2018
Last Updated: February 3, 2017
Last Verified: February 2017