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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 (G-FORCE-1)

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by EpicentRx, Inc.
Sponsor:
Information provided by (Responsible Party):
EpicentRx, Inc.
ClinicalTrials.gov Identifier:
NCT02871843
First received: August 11, 2016
Last updated: July 2, 2017
Last verified: February 2017
  Purpose

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 Intervention 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
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
3+3 Dose Escalation
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by EpicentRx, Inc.:

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

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 39
Actual Study Start Date: February 14, 2017
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Radiation: Radiation
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02871843

Contacts
Contact: Meaghan Stirn 8588122069 info@epicentrx.com
Contact: Scott Caroen 8588122069 info@epicentrx.com

Locations
United States, California
University of California San Francisco (UCSF) Recruiting
San Francisco, California, United States, 94143
Contact: Jane Rabbitt    415-353-2652    Jane.Rabbitt@ucsf.edu   
Contact: Thelma Munoz    415-353-2523    Thelma.Munoz@ucsf.edu   
Principal Investigator: Nicholas Butowski, MD         
United States, New Jersey
The Cancer Institute of New Jersey (Rutgers University) Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Ling Zheng    732-235-8865    Zhengl1@cinj.rutgers.edu   
Principal Investigator: Robert Aiken, MD         
United States, New York
Weill Cornell Brain Tumor Center Recruiting
New York, New York, United States, 10021
Contact: Kate Carbonell    646-962-6137    kac2051@med.cornell.edu   
Principal Investigator: Howard A Fine, MD         
Sponsors and Collaborators
EpicentRx, Inc.
  More Information

Responsible Party: EpicentRx, Inc.
ClinicalTrials.gov Identifier: NCT02871843     History of Changes
Other Study ID Numbers: RRx001-17-02
Study First Received: August 11, 2016
Last Updated: July 2, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioblastoma
Oligodendroglioma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 22, 2017