RRx-001 + Radiation + Temozolomide In Newly Diagnosed Glioblastoma and Anaplastic Gliomas

NCT02871843 | Completed Phase 1 FDA Drug

• 1 other identifier: RRx001-17-02
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

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 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

Conditions

Glioblastoma; Oligodendroglioma; Anaplastic Oligodendroglioma

Outcome Measures

Primary Outcomes (1)

• Number, frequency and type of adverse events

  12 weeks

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  4 months

• Clinical Benefit Rate (CBR)

  4 months

• Intracranial Progression Free Survival

  4 months

• Overall Survival

  1 year

Study Arms (1)

Escalation of RRx-001 with TMZ + RT

EXPERIMENTAL

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; Radiation: Radiation; Drug: Fixed dose Temozolomide (75 mg/m2); Drug: TMZ Maintenance

Interventions

RRx-001 dose escalation with TMZ + RT DRUG

Dose escalation of RRx-001. Dose levels of 0.5, 1.0, 2.0 and 4.0 mg, once weekly.

Escalation of RRx-001 with TMZ + RT

Radiation RADIATION

Conformal or intensity-modulated radiotherapy (60 Gy in 2 Gy fractions) given 5 days a week for 30 fractions (about 6 weeks)

Escalation of RRx-001 with TMZ + RT

Fixed dose Temozolomide (75 mg/m2) DRUG

Oral temozolomide 75 mg/m2 daily for 6 weeks

Also known as: TMZ

Escalation of RRx-001 with TMZ + RT

TMZ Maintenance DRUG

TMZ maintenance at 150-200 mg/m2

Escalation of RRx-001 with TMZ + RT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of high-grade glioma, including anaplastic glioma (WHO grade III with 1p/19q chromosomes intact), glioblastoma (WHO grade IV) or gliosarcoma (WHO Grade IV);
• The tumor must not have an infratentorial component;
• The patient must have recovered from the effects of surgery, postoperative infection and other complications before enrollment;
• Estimated survival of at least 12 weeks;
• Karnofsky Performance Score of ≥ 70% at the time of entry
• Stable or decreasing steroid dose within 2 weeks of first dose of study drug if patient is taking steroids. No steroid use is also acceptable.
• Neurological stability for at least 14 days prior to first dose of study drug;
• Acceptable liver function at Screening,
• Serum creatinine \< 1.5x institution upper limit of normal
• Acceptable hematologic status at Screening
• Female subjects of childbearing potential, and male subjects with partners of childbearing potential, must agree to use medically acceptable methods of contraception.

You may not qualify if:

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
• Recurrent malignant gliomas previously treated with radiotherapy and/or chemotherapy
• Metastases detected below the tentorium or beyond the cranial vault, including tumors with evidence of leptomeningeal metastases as previously indicated;
• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide. Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted;
• Prior radiotherapy to the head or neck (except for T1 glottic cancer), that would result in overlap of radiation fields.
• Active connective tissue disorders, such as lupus or scleroderma that in the opinion of the treating physician may put the patient at high risk for radiation toxicity;
• Unresolved toxicity higher than CTCAE (v. 4.03) Grade 1 attributed to any prior therapy/procedure excluding alopecia and hypothyroidism;
• Acquired immune deficiency syndrome (AIDS) due to the potential for increased complications from treatment; note, however, that HIV testing is not required
• No other concurrent chemotherapeutic or investigational agents for this cancer. However, concurrent glucocorticoids are allowed;
• Inability to swallow pills;
• Serious co-morbid medical conditions, or a clinically significant laboratory finding(s) or any finding(s) on history and/or examination that, in the opinion of the Investigator, could interfere with the conduct of the study or could put the patient at unacceptable risk;
• Patients who are pregnant or lactating or who are planning to become pregnant during the course of the study are excluded.

Sponsors & Collaborators

• EpicentRx, Inc.: lead

Study Sites (3)

University of California San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

The Cancer Institute of New Jersey (Rutgers University)

New Brunswick, New Jersey, 08903, United States

Location

Weill Cornell Brain Tumor Center

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Glioblastoma; Oligodendroglioma

Interventions

Temozolomide; Radiation

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena

Study Officials

• Bryan Oronsky

  Chief Medical Officer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 Dose Escalation

Study Record Dates

• First Submitted: August 11, 2016
• First Posted: August 18, 2016
• Study Start: February 14, 2017
• Primary Completion: October 11, 2019
• Study Completion: September 19, 2021
• Last Updated: May 16, 2022

Record last verified: 2022-05

Locations

US (3)