QUILT-3.011 Phase 2 Yeast-Brachyury Vaccine Chordoma

Chordoma Clinical Trial

Official title: A Randomized, Double-Blind, Phase 2 Trial of GI-6301 (Yeast-Brachyury Vaccine) Versus Placebo in Combination With Standard of Care Definitive Radiotherapy in Locally Advanced, Unresectable, Chordoma

Status Active, not recruiting

Clinical Trial Summary

TRIAL SUMMARY

Researchers at the National Cancer Institute (NCI) are now enrolling patients in a phase 2 clinical trial to determine whether the yeast-brachyury vaccine GI-6301 improves the effectiveness of radiation for patients with localized chordoma. Chordoma patients with inoperable or residual tumor who do not have metastases and are planning to be treated with definitive (>70Gy) radiation are eligible to participate. Patients will initially be randomized to receive radiation plus the vaccine or radiation plus a blinded placebo. Those randomized to receive radiation plus placebo will have the option to receive vaccine if their tumor grows while on the study. The study will compare the outcomes of patients treated with radiation with and without the vaccine to determine whether the vaccine can increase the chances of shrinking the tumor and/or preventing further tumor growth.

WHY THIS TRIAL IS BEING DONE

The primary treatment options for chordoma currently consist of surgery and high dose radiation. Radiation has been shown to improve patient outcomes following surgery. Radiation is also sometimes used instead of surgery when surgery would carry unacceptable risks.

The chance of tumor growth after radiation is significantly higher for patients who have residual tumor than for those whose tumor is completely removed. Unfortunately for patients with a tumor that cannot be completely removed, there tends to be a short time until the tumor grows back and eventually causes death. For this reason, our team at the NCI seeks to identify a therapy that can reduce the risk of recurrence and improve survival after radiation for patients who have residual tumor.

One approach we are pursuing is treating patients with a therapeutic vaccine that is intended to stimulate the immune system to fight cancer cells that express the brachyury protein. Brachyury is present at very high levels in nearly all chordomas but is not present in the vast majority of normal tissues, making it a promising target for immune therapy. Research in other cancers suggests that radiation in combination with immune therapy can provide powerful antitumor effects.

We have recently completed a phase 1 clinical trial of a therapeutic vaccine targeting brachyury called GI-6301 in which 11 chordoma patients participated. Through that phase I trial, we learned that this vaccine can be given safely without serious adverse reactions. In that study, the vaccine was also capable of inducing immune responses against brachyury and one patient had his tumor shrink more than 30% while on study. Some other patients (7 of 10 evaluable) also had stable disease for more than 5 months while on study. However, these clinical findings are not definitive and further clinical testing is required to determine the benefit of this vaccine in chordoma. To that end, we have designed a larger phase 2 clinical trial intended to determine if this vaccine, when given in combination with radiation, improves outcomes for patients with chordoma compared to those who only have radiation.

WHO CAN PARTICIPATE

We have designed this trial for patients who have residual tumor remaining after surgery, who are unable to have surgery, or who have a local recurrence following previous treatment.

To be eligible for enrollment on this study, patients must:

• Have a confirmed diagnosis of chordoma

• Have only localized tumor (no metastases)

• Be able to receive at least 70 Gy of radiation to their localized tumor

• Be willing to travel to Bethesda, MD for treatment and follow-up visits

HOW THE TRIAL WILL WORK

The trial is taking place at the National Institutes of Health Clinical Center in Bethesda, MD. The NCI will pay for transportation costs (including airfare) and a portion of lodging costs for patients after enrollment in this study.

The process of participating in the trial is as follows:

• Patients travel to NIH to receive injections of the vaccine (or placebo) every other week for three doses prior to starting radiation (approximately 4 weeks)

• Patients then complete their radiation treatment with their home radiation oncologist (typically over a 1-2 month timespan)

• Following completion of radiation treatment plan, patients travel back to NIH to resume vaccine (or placebo) injections every 2 weeks until 6 total doses have been given (3 doses after radiation, another 4 weeks)

• At that point, doses spread out to every 4 weeks for 4 doses, and then 1 dose every 3 months until disease progression.

• Between all doses of vaccine, patients may return home and travel back for the next visit. There is no requirement to stay locally in Bethesda at any point in the study outside of clinic visits and dosing days.

• Repeat imaging studies will be performed about 3 months after completion of radiatio...

Clinical Trial Description

BACKGROUND:

• Chordoma is a rare disease, affecting about 3,000 people in the United States, with about 300 new cases diagnosed per year.

• Brachyury is a member of the T-box family of transcription factors, characterized by a highly conserved DNA-binding domain designated as T-domain.

• Brachyury is expressed universally in chordoma cells.

• GI-6301 (Yeast-brachyury vaccine) has demonstrated immunogenicity with a tolerable and acceptable safety profile in a phase 1 trial.

• Brachyury specific T cells can lyse human cancer cells expressing brachyury in an MHC restricted manner.

• There have been indications of clinical benefit in patients with chordoma enrolled on the phase I trial of GI-6301.

A) 1 Partial Response

B) 1 Mixed Response in Chordoma patients who received Radiation

C) 6 of 9 patients with progressive disease at enrollment had Stable Disease at Day 85 restaging

-In vitro, chordoma cell lines are killed significantly better by brachyury-specific T cells after radiation exposure using either proton beam or gamma radiation.

ENDPOINTS:

PRIMARY OBJECTIVES:

-To determine if there is a difference in overall response rate (ORR) defined as complete response (CR) or partial response (PR) by RECIST 1.1 after up to 24 months among patients with Chordoma who are treated with radiation plus placebo vs. radiation plus vaccine.

ELIGIBILITY:

• Patients at least 18 years old with locally advanced (unresectable, non-metastatic) chordoma who are eligible for definitive radiotherapy treatment.

• No history of autoimmune disease

• Measurable disease as defined by RECIST 1.1

• Adequate organ function

DESIGN:

• Randomized, double-blind, placebo controlled phase 2 clinical trial of radiation plus placebo vs. radiation plus yeast-brachyury vaccine in patients with chordoma.

• Participants will be randomized on a 1:1 basis to the two arms

• Participants assigned to the placebo arm will be allowed to cross-over at time of confirmed disease progression.

• Participants will be evaluated for objective response, progression free survival and overall survival

• Up to 55 participants will be accrued to the study ;

Related Conditions & MeSH terms

• Chordoma

• NCT number: NCT02383498
• Study type: Interventional
• Source: NantCell, Inc.
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 17, 2015
• Completion date: March 31, 2020