Neoplasms

All Conditions

Rare Diseases

Chordoma

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Oculocerebral Syndrome With Hypopigmentation

All Drugs and Chemicals

Other Dietary Supplements

Vaccines

Brewer's Yeast

Placebo will consist of USP-grade or equivalent 0.9% Sodium Chloride for Injection. Doses of placebo will be drawn into labeled syringes by an independent, unblinded pharmacist or designee.

Placebo

GI-6301 Vaccine is a heat-killed, recombinant yeast-based vaccine engineered to express the transcription factor, Brachyury. The Brachyury gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wildtype yeast) to produce the final recombinant vaccine product.

GI-6301 Vaccine (Yeast- Brachyury)

Radiotherapy

wGT3X-BT is small, non-invasive, portable watch accelerometer worn on the subject's wrist for Cycle 1 through Cycle 9

wGT3X-BT Actigraph

This is 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 were enrolled. Patients were randomized to receive radiation plus the vaccine or radiation plus a blinded placebo. The study compared 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.

Chordoma is a rare disease, affecting about 3,000 people in the United States. There have been indications of clinical benefit in patients with chordoma enrolled on the phase I trial of GI-6301.

PRIMARY OBJECTIVE: 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.

QUILT-3.011 Phase 2 Yeast-Brachyury Vaccine Chordoma

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

Difference in overall response rate among patients with Chordoma who are treated with radiation plus placebo vs. radiation plus vaccine.

Overall response rate (ORR) defined as complete response (CR) or partial response (PR) by RECIST 1.1 in the irradiated tumor site after up to 24 months among patients with Chordoma who are treated with radiation plus vaccine vs. radiation plus placebo

Complete response (CR; disappearance of all target lesions and no new lesions) or partial response (PR; \>=30% decrease in the sum of the greatest diameter).

National Cancer Institute (NCI)

NantCell, Inc.

Radiation + GI-6301 Vaccine + Actigraph

GI-6301 Vaccine (Yeast- Brachyury): GI-6301 Vaccine is a heat-killed, recombinant yeast-based vaccine engineered to express the transcription factor, Brachyury. The Brachyury gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wildtype yeast) to produce the final recombinant vaccine product.

Radiotherapy: Standard of care

wGT3X-BT Actigraph: wGT3X-BT is small, non-invasive, portable watch accelerometer worn on the subject's wrist for Cycle 1 through Cycle 9

GI-6301 Vaccine

Radiation + GI-6301 Placebo + Actigraph

GI-6301 Placebo: GI-6301 Placebo will consist of USP-grade or equivalent 0.9% Sodium Chloride for Injection. Doses of GI-6301 placebo will be drawn into labeled syringes by an independent, unblinded pharmacist or designee.

Radiotherapy: Standard of care

wGT3X-BT Actigraph: wGT3X-BT is small, non-invasive, portable watch accelerometer worn on the subject's wrist for Cycle 1 through Cycle 9

Vaccine

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Subjects with Locally Advanced, Unresectable, Chordoma

Sandeep Bobby Reddy, Chief Medical Officer

Overall Response Rate

Overall Study

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Analgesics

Herbal and Botanical

Nivolumab

Pembrolizumab

Immunomodulating Agents

Ipilimumab

Interleukin-2

Analgesics, Non-Narcotic

Cola

\[18F\]FB-IL2 PET scan, Tumor biopsy, CT scan, Biopsy of non-target tissue

All patients in this study will undergo a IL2 PET scan at baseline and week 6 of treatment with immunotherapy.

IL2-PET scan

A procedure to acquire tissue of a predetermined melanoma metastasis will be performed in all patients that participate in phase 2 of this study.

Tumor biopsy

A CT scan of diagnostic quality will accompany all the PET scans and will additionally been made 12 and 16 weeks after start of immunotherapy to evaluate response to treatment.

CT scan

A biopsy of skin and colon non-target tissue involved in an immune-related side effect is optional in patients that participate in phase 2 of this study.

Biopsy of non-target tissue

G. A. Hospers, MD, PhD

T cell infiltration of tumor lesions is a known prognostic factor in several tumor types and is used as treatment mechanism in some of these tumor types. In metastatic melanoma, treatment with immune checkpoint inhibitors induces clinical benefit in about 30-50% of the patients. These immune-based therapies are however accompanied by serious immune-related adverse events and high costs.

Tumor infiltrating T cells express the high affinity interleukin-2 (IL2) receptor on their surface. These T cells could therefore be visualized by molecular imaging with a radio-labelled ligand for this receptor. For this purpose, the investigators have developed the PET tracer \[18F\]FB-IL2.

The study commences with a biodistribution study (phase 1) in 5 subjects. Thereafter the main study (phase 2) starts, in which 25 subjects will receive two \[18F\]FB-IL2 PET scans at baseline and week 6 of treatment with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab. If \[18F\]FB-IL2 PET is able to detect a response to treatment, it could serve as a non-invasive early indicator of T cell response to the treatment. Besides, accumulation of the PET tracer in non-target tissue could indicate infiltration of activated T cells in normal organs and thus may predict the development of an immune-related adverse event.

IL2 Imaging in Metastatic Melanoma

[18F]FB-IL2 Imaging of T Cell Response as Biomarker to Guide Treatment Decisions in Metastatic Melanoma Patients

Biodistribution and kinetics will be assessed in the first five patients that participate in this trial (phase 1). A 60-minute dynamic PET scan of the chest and 2 total-body PET scans at 60 and 120 minutes will be acquired to determine tracer kinetics and residence time of the tracer in major organs.

For detection of a treatment-induced immune response the absolute tracer uptake in tumor lesions will be compared between the scan at baseline and the scan after 6 weeks of treatment with ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab.

The amount of IL2 receptor positive cells will be scored by immunohistochemical staining of tumor biopsy material and will be correlated to the tumor uptake of \[18F\]FB-IL2.

The increase in tumor uptake of \[18F\]FB-IL2 ofu the tumor lesions on the PET scan at baseline and week 6 of treatment with immunotherapy, will be correlated to radiological response as measured on the CT scans at week 6, 12 and 16 according to the RECIST 1.1 criteria.

Both the heterogeneity between separate lesions in one patient and between lesions in different patients will be determined and if possible will be correlated to treatment response (lesion based).

Treatment induced immune cell activation in non-target tissue will be determined by visually comparing the PET results at baseline and after 6 weeks of treatment. In regions with a higher tracer uptake on the week 6 scan the absolute uptake will be determined and this will be correlated to the development of an immune-related adverse event. In case of immune-related side effects localized to the skin or colon, biopsy samples are optional and tissue infiltration of IL2 receptor positive cells can be correlated to \[18F\]FB-IL2 uptake on PET.

Adverse events will be recorded. Vital signs and blood parameters will be determined before and after tracer injection and directly after the PET scan for safety reasons.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
QUILT-3.011 Phase 2 Yeast-Brachyury Vaccine Chordoma	NCT02383498	Chordoma	Placebo GI-6301 Vaccine... Radiotherapy wGT3X-BT Actigr...	18 Years - 100 Years	NantCell, Inc.
IL2 Imaging in Metastatic Melanoma	NCT02922283	Melanoma	IL2-PET scan Tumor biopsy CT scan Biopsy of non-t...	18 Years -	University Medical Center Groningen
QUILT-3.011 Phase 2 Yeast-Brachyury Vaccine Chordoma	NCT02383498	Chordoma	Placebo GI-6301 Vaccine... Radiotherapy wGT3X-BT Actigr...	18 Years - 100 Years	NantCell, Inc.

Spots Global Cancer Trial Database for t cell response