Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab

NCT01403610 | Completed Phase 2 Results

• 1 other identifier: CTRC 11-24
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The Primary Objectives are:

• To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue
• To assess the safety of single dose TH-302 in patients with high grade glioma undergoing surgery
• To assess the safety of TH-302 in combination with bevacizumab for patients with high grade glioma
• To determine the MTD and DLT(s) of TH-302 in combination with bevacizumab The Secondary Objectives are: To determine the progression-free survival with or without debulking craniotomy for patients treated with combination bevacizumab and TH-302 following recurrence on single agent bevacizumab

Conditions

HIGH GRADE GLIOMA

Keywords

TH-302; Bevacizumab; Phase 2; Glioma; High Grade Glioma; CNS

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  Time from initiation study until radiographic progression by RANO criteria

  2 years

Study Arms (4)

Cohort 1

EXPERIMENTAL

Subjects received TH-302 single dose at 575 mg/m2 or placebo administered preoperative in a 2:1 randomization and were then administered 240 mg/m2 of TH-302 post-operative.

Drug: TH-302 preoperative; Drug: Placebo; Drug: TH-302 (escalating) with bevacizumab 10mg/kg

Cohort 2

EXPERIMENTAL

Surgical subjects will receive TH-302 at 340 mg/m2 every 2 weeks (4 week cycles) starting after surgery from Cycle 1, Day 1 until disease progression.

Drug: TH-302 preoperative; Drug: TH-302 (escalating) with bevacizumab 10mg/kg

Cohort 3

EXPERIMENTAL

Surgical or Non-Surgical subjects will receive TH-302 at 480 mg/m2 every 2 weeks (4 week cycles) starting after surgery from Cycle 1, Day 1 until disease progression.

Drug: TH-302 (escalating) with bevacizumab 10mg/kg

Cohort 4

EXPERIMENTAL

Non-surgical subjects will receive a dose up to 670 mg/m2 of TH-302

Drug: TH-302 (escalating) with bevacizumab 10mg/kg

Interventions

TH-302 preoperative DRUG

TH-302 single dose at 575 mg/m2 administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302.

Also known as: Study drug

Cohort 1; Cohort 2

Placebo DRUG

Placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302.

Also known as: Study placebo

Cohort 1

TH-302 (escalating) with bevacizumab 10mg/kg DRUG

Combination of 10mg/m2 of bevacizumab with an escalating dose of TH-302 from 240 to 670 mg/m2

Also known as: Study drug escalating dose

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
• Histologically confirmed high grade astrocytoma
• Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as anti-angiogenic therapy (ie, bevacizumab)
• Recovered from toxicities of prior therapy to grade 0 or 1
• ECOG performance status of 0 or 1
• Life expectancy of at least 3 months
• Acceptable liver function
• Acceptable renal function
• Acceptable hematologic status
• All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose

You may not qualify if:

• The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.
• The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
• The subject is unable to undergo MRI scan (eg, has pacemaker).
• The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
• The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug.
• The subject has evidence of wound dehiscence
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation \<90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
• The subject is pregnant or breast-feeding.
• The subject has serious intercurrent illness
• The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• The subject has received any of the following prior anticancer therapy:
• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed
• Antiangiogenic agents whose primary mode of action is through the VEGF signaling within 21 days prior to first dose of study drug (surgical subjects only)
• Non-bevacizumab systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug
• Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Cancer Therapy & Research Center at UTHSCSA

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

Drug Evaluation; TH 302

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Results Point of Contact

• Title: Andrew Brenner
• Organization: UT Health San Antonio

regulatoryaffairs@uthscsa.edu

210-450-1000

Study Officials

• Andrew Brenner, MD,

  Institute for Drug Development

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2011
• First Posted: July 27, 2011
• Study Start: June 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: July 24, 2019
• Results First Posted: July 24, 2019

Record last verified: 2019-03

Locations

US (1)