CTX131 for Resistant or Recurrent Cancer

Recruiting at6 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: CRISPR Therapeutics AG

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS, Cardiac, Pulmonary, Infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing CTX131, a treatment that uses modified immune cells to fight cancer, in patients whose cancer has come back or didn't respond to other treatments. The immune cells are changed using gene-editing technology to help them attack the cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on steroids or other immunosuppressive therapy for an autoimmune disease, you may not be eligible to participate.

What data supports the effectiveness of the drug CTX131 for resistant or recurrent cancer?

Research on similar treatments, like cyclophosphamide (CTX) used in combination with other drugs, shows that it can help patients with advanced prostate and breast cancer by slowing disease progression and providing prolonged clinical benefits. This suggests that CTX131, which may include similar components, could potentially be effective for resistant or recurrent cancer. ^{1 2 3 4 5}

What safety data exists for CTX131 or similar treatments in humans?

The research does not provide specific safety data for CTX131 or its variants, but a related treatment, C-1311, was evaluated for safety in a phase 1 trial for patients with advanced solid tumors, focusing on its safety and tolerability. ^{6 7 8 9 10}

How is the treatment CTX131 different from other treatments for resistant or recurrent cancer?

CTX131 is unique because it targets cancer stem cells, which are often responsible for resistance to traditional treatments. This approach may improve outcomes by addressing the root cause of treatment resistance. ^{8 9 10 11 12}

Research Team

Alissa Keegan, MD, PhD

Principal Investigator

CRISPR Therapeutics

Eligibility Criteria

Adults over 18 with certain advanced cancers (like kidney, cervical, pancreatic cancer, and mesothelioma) that have come back or didn't respond to treatment. They must be in good physical condition and agree to use birth control for a year after getting the study drug.

Inclusion Criteria

I agree to use birth control from enrollment until at least 12 months after my treatment.

I am 18 years old or older.

My cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

I have a history of specific brain, heart, or lung conditions.

I am not pregnant or breastfeeding.

I have an immune system disorder or autoimmune disease and need steroids or other treatments to manage it.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CTX131 infusion

1-2 weeks

Treatment

CTX131 is administered by IV infusion following lymphodepleting chemotherapy

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

Treatment Details

Interventions

• CTX131 (CAR T-cell Therapy)

Trial Overview The trial is testing CTX131's safety and effectiveness on patients with specific solid tumors that are either untreatable or have returned after treatment. It's an early-phase study where everyone gets the same experimental therapy.

Participant Groups

Group I: CTX131 Experimental Treatment 1 Intervention

Administered by IV infusion following lymphodepleting chemotherapy.

Who Is Running the Clinical Trial?

CRISPR Therapeutics AG

Lead Sponsor

Trials

9

Recruited

640+

Findings from Research

In a phase II study involving 68 women with metastatic breast cancer, the combination of oral metronomic cyclophosphamide and capecitabine showed a median time to progression of 5.2 months and a median overall survival of 16.9 months, indicating its efficacy as a treatment option.

The treatment was well tolerated, with only anorexia being a significant grade 3/4 adverse event in 7.5% of patients, suggesting a favorable safety profile for this all-oral regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: a phase II study. Wang, Z., Lu, J., Leaw, S., et al.[2022]

Low-dose metronomic chemotherapy using cyclophosphamide and methotrexate showed a 15.7% rate of prolonged clinical benefit in patients with metastatic breast cancer, with a median follow-up of 23 months.

Among the 153 patients studied, some achieved significant responses, including complete remission lasting up to 42 months after stopping treatment, highlighting the potential of this approach as an effective therapy for metastatic breast carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer. Orlando, L., Cardillo, A., Rocca, A., et al.[2022]

In a study of 74 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel, certain circulating tumor cell (CTC) gene expressions, such as AR-V7 and EPCAM, were significantly associated with overall survival, indicating their potential as prognostic biomarkers.

Patients treated with a lower dose of cabazitaxel (20 mg/sqm) who were AR-V7 positive had a notably shorter median overall survival (6.6 months) compared to AR-V7 negative patients (14 months), suggesting that AR-V7 positivity may indicate poorer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel. Gurioli, G., Conteduca, V., Brighi, N., et al.[2022]

In a study of 28 patients with advanced castrate-resistant prostate cancer (CRPC), second-line chemotherapy using capecitabine, cyclophosphamide, thalidomide, and prednisone showed promising efficacy, with 35.7% of patients experiencing a significant decrease in prostate-specific antigen levels.

The treatment demonstrated an excellent safety profile, as no patients experienced severe (grade 3-4) toxicities, while the median overall survival was 19.5 months, indicating that this combination therapy is both effective and safe for advanced CRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients. Meng, LJ., Wang, J., Fan, WF., et al.[2021]

In a study of 58 patients with metastatic castration-resistant prostate cancer (CRPC) who progressed after docetaxel, 25% showed a significant PSA response (≥50% reduction), indicating that low-dose oral cyclophosphamide and methotrexate can be effective in this population.

The treatment was generally well-tolerated, with manageable toxicity; however, some patients experienced grade 3 leukopenia and thrombocytopenia, suggesting that while the regimen is feasible, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel. Gebbia, V., Serretta, V., Borsellino, N., et al.[2018]

In a study of 49 colon cancer patients, co-expression of CXCR4 and CD133 was found to be significantly associated with poorer prognosis, as indicated by a 3-year survival rate of only 27.3% for those with co-expression compared to 76.3% for others.

The expression of CXCR4 and CD133 was linked to advanced TNM staging and lymphatic metastasis, suggesting that these markers could help identify patients at higher risk for aggressive disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CXCR4 and CD133 co-expression on the prognosis of patients with stage II~III colon cancer. Li, XF., Guo, XG., Yang, YY., et al.[2019]

C-1311, an anticancer agent, was tested in a phase 1 trial with 22 patients, showing a recommended dose of 480 mg/m² that provided a predictable safety profile and good tolerability, despite all patients experiencing treatment-related adverse events.

The most common side effects included neutropenia and nausea, with some severe cases of neutropenia, indicating that while C-1311 has potential anti-tumor activity, careful monitoring of blood-related side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. Isambert, N., Campone, M., Bourbouloux, E., et al.[2017]

Anti-CD133 CAR-T cells effectively target and kill cisplatin-resistant gastric cancer stem cells, showing increased activation and cytokine production after treatment, which suggests a strong immune response.

The combination of cisplatin and anti-CD133 CAR-T therapy significantly reduces tumor growth and the presence of cancer stem cells in multiple xenograft models, indicating a promising strategy for improving treatment outcomes in aggressive gastric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy. Han, Y., Sun, B., Cai, H., et al.[2021]

In a study of 32 rectal cancer patients, higher expression of CD133 was linked to greater sensitivity to preoperative radiotherapy, suggesting it could be a useful biomarker for predicting treatment response.

The research found that CD133 expression and the differentiation of rectal cancer are independent predictive factors for how well patients respond to radiotherapy, highlighting the potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Association of CD133 expression and sensitivity of rectal cancer to preoperative radiotherapy]. Qiu, JM., Yang, GG., Lu, XJ., et al.[2018]

In a study of 105 patients with locally advanced rectal cancer, CD133 expression significantly increased after neoadjuvant chemoradiotherapy (nCRT), indicating that nCRT may enhance CD133 levels in rectal cancer tissues.

Patients with CD133-positive tumors showed a lower response to nCRT, suggesting that targeting CD133 could potentially improve the effectiveness of nCRT in treating rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression of CD133 in rectal cancer tissues and its relationship with neoadjuvant chemoradiotherapy]. Li, D., Wu, H., Feng, R., et al.[2020]

Radioimmunotherapy (RIT) using the 131I-AC133.1 monoclonal antibody effectively targeted CD133(+) colonic cancer stem cells in tumor-bearing mice, leading to significantly longer survival times and slower tumor growth compared to control groups.

The treatment resulted in lower levels of cancer stem-like biomarkers and higher levels of E-cadherin, indicating a reduction in cancer stem cell characteristics and promoting tumor necrosis, which suggests that RIT can effectively inhibit tumor development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy for CD133(+) colonic cancer stem cells inhibits tumor development in nude mice. Weng, D., Jin, X., Qin, S., et al.[2018]

In ovarian cancer cell lines, specifically OVCAR-3, -4, and -5, the combination of CD133 and CXCR4 markers identified a population with strong cancer stem cell characteristics, which was linked to enhanced tumor formation in animal models.

The CD133(+)CXCR4(+) cells showed resistance to cisplatin and overexpressed the ABCG2 drug transporter, indicating that targeting this specific cell population could be a promising strategy for overcoming chemotherapy resistance in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a distinct population of CD133(+)CXCR4(+) cancer stem cells in ovarian cancer. Cioffi, M., D'Alterio, C., Camerlingo, R., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: a phase II study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer. [2022]

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

Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients. [2021]

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

Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel. [2018]

6. Thailand pubmed.ncbi.nlm.nih.gov

Effect of CXCR4 and CD133 co-expression on the prognosis of patients with stage II~III colon cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours. [2017]

8. Germany pubmed.ncbi.nlm.nih.gov

Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy. [2021]

9. China pubmed.ncbi.nlm.nih.gov

[Association of CD133 expression and sensitivity of rectal cancer to preoperative radiotherapy]. [2018]

10. China pubmed.ncbi.nlm.nih.gov

[Expression of CD133 in rectal cancer tissues and its relationship with neoadjuvant chemoradiotherapy]. [2020]

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

Radioimmunotherapy for CD133(+) colonic cancer stem cells inhibits tumor development in nude mice. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Identification of a distinct population of CD133(+)CXCR4(+) cancer stem cells in ovarian cancer. [2021]