GCAR1 for Sarcoma

(SPS-Q2 Trial)

Age: Any Age

Sex: Female

Trial Phase: Phase < 1

Sponsor: University of Calgary

Disqualifiers: Uncontrolled infection, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 6-7 months

Trial Summary

What is the purpose of this trial?

A single patient study to determine whether GCAR1 is safe and effective for re-treatment of alveolar soft part sarcoma (ASPS) with GPNMB surface expression that has relapsed and is not responding to usual treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had anti-cancer therapy within 21 days before starting the trial treatment.

What safety data exists for GCAR1 or similar treatments in humans?

The safety profiles of similar treatments, like larotrectinib and entrectinib, show that common side effects include dizziness and pain, but no major long-term safety concerns have been identified. These treatments have been used in cancer patients, and continuous safety monitoring is recommended to detect any new adverse reactions. ^{1 2 3 4 5}

How does the GCAR1 treatment differ from other sarcoma treatments?

GCAR1, likely a form of CAR-T cell therapy, is unique because it uses modified immune cells to specifically target and attack sarcoma cells, unlike traditional treatments that may not be as targeted. This approach has shown promise in other cancers and is being explored for its potential to improve outcomes in sarcoma patients. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for patients with a rare cancer called Alveolar Soft Part Sarcoma (ASPS) that has come back after treatment. They must be healthy enough in terms of kidney function and heart strength, not have active infections, and can't be pregnant or breastfeeding. Also, they should not have had any cancer treatments in the last 3 weeks.

Inclusion Criteria

The patient must provide informed consent

My kidneys and heart are functioning well.

Exclusion Criteria

I do not have any ongoing infections that aren't under control.

Pregnancy or nursing

I haven't had cancer treatment in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Standard lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide before each GCAR1 infusion

5 days

Treatment

Two-dose escalation study with intravenous infusions of GCAR1, with at least three months between infusions

6-7 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with diagnostic imaging at specified intervals

1 year

5 visits (in-person)

Treatment Details

Interventions

• GCAR1

Trial Overview The study is testing GCAR1, a CAR T therapy designed to target ASPS cells that show GPNMB on their surface. It's an experimental approach being tried out on one patient to see if it's safe and works better than current treatments for this relapsed cancer.

Participant Groups

Group I: GCAR1 Experimental Treatment 1 Intervention

This is an intrapatient two-dose escalation study. The patient will receive two separate intravenous infusions of cryopreserved, autologous GCAR1, with at least three months (+/- 30 days) between infusions. Both infusions will be preceded by standard lymphodepleting chemotherapy (Fludarabine 40 mg/m2 x 3 days, cyclophosphamide 600 mg/m2 x 2 days) . Dose 1 will be 5.0E6 CAR+ T cells/kg patient body weight, Dose 2 will be 2.5E7 CAR+ T cells/kg patient body weight. Infusions will be intravenous, single infusions.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Alberta Health Services, Calgary

Collaborator

Trials

15

Recruited

2,600+

Alberta Precision Laboratories

Collaborator

Findings from Research

A systematic review of 26 studies on multi-targeted kinase inhibitors for advanced cancer revealed that common side effects include diarrhea, fatigue, nausea, and hypertension, affecting more than 10% of patients.

While adverse events are frequent with multi-kinase inhibitors, serious side effects are less common compared to traditional cytotoxic cancer therapies, indicating a potentially safer profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of multi-targeted kinase inhibitors as monotherapy treatment of cancer: a systematic review of the literature. Crean, S., Boyd, DM., Sercus, B., et al.[2019]

Larotrectinib and entrectinib, first-generation TRK inhibitors, are effective first-line treatments for advanced non-small cell lung cancer (NSCLC) with TRK gene fusions, showing rapid and long-lasting clinical benefits.

A safety analysis of 807 reports revealed that the most common adverse reactions were dizziness and pain, with no significant long-term safety concerns noted, indicating a favorable risk-benefit profile for these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. Liguori, V., Gaio, M., Zinzi, A., et al.[2023]

A machine-learning model was developed using data from 4638 patients across 16 FDA-approved small molecule kinase inhibitors (SMKIs) to analyze the relationship between kinase targets and adverse events (AEs), providing a new tool for predicting safety risks in cancer treatments.

The model not only helps identify potential kinase-inhibitor adverse event pairs but also serves as a precision medicine tool to enhance patient safety by forecasting clinical safety signals and aiding in the development of safer SMKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. Gong, X., Hu, M., Liu, J., et al.[2022]

A study analyzing 1568 reported cases of ocular adverse effects (OAEs) from BRAF and MEK inhibitors found that BRAF monotherapy is significantly linked to various eye issues, including iris and ciliary body abnormalities and anterior uveitis, indicating a need for careful monitoring of these side effects.

MEK inhibitor monotherapy was associated with retinal and choroid abnormalities, and the combination therapy of BRAF and MEK inhibitors showed potential for increased ocular toxicity, suggesting that personalized management strategies are necessary for patients undergoing combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database. Mettler, C., Monnet, D., Kramkimel, N., et al.[2021]

In a study of 466 metastatic renal cell carcinoma (mRCC) patients treated between 2007 and 2011, 85.8% experienced at least one adverse event (AE), with fatigue, vomiting, and diarrhea being the most common.

The study revealed that younger patients (<65 years) had higher rates of AEs compared to older patients, highlighting the importance of closely monitoring and managing AEs in real-world settings, as their frequency and severity can differ from those reported in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice. Hirsch, BR., Harrison, MR., George, DJ., et al.[2021]

CAR T Cell therapy is a promising new treatment for sarcomas, which have seen stagnant survival rates, particularly in recurrent or metastatic cases, highlighting the urgent need for novel therapies.

Recent studies have identified several sarcoma-associated antigens suitable for CAR T Cell targeting, such as HER2 and GD2, showing encouraging results and suggesting that this therapy could improve outcomes for sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications. Thanindratarn, P., Dean, DC., Nelson, SD., et al.[2020]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Safety of multi-targeted kinase inhibitors as monotherapy treatment of cancer: a systematic review of the literature. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Safety Profiles of Two First-Generation NTRK Inhibitors: Analysis of Individual Case Safety Reports from the FDA Adverse Event Reporting System (FAERS) Database. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Discovery of targeted expression data for novel antibody-based and chimeric antigen receptor-based therapeutics in soft tissue sarcomas using RNA-sequencing: clinical implications. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Functional genomics of human clear cell sarcoma: genomic, transcriptomic and chemical biology landscape for clear cell sarcoma. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

MAGE-A3 is a Clinically Relevant Target in Undifferentiated Pleomorphic Sarcoma/Myxofibrosarcoma. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trials for sarcomas: the cutting edge. [2014]