CYT-0851 for Cancer

Recruiting at 17 trial locations

Overseen By Pamela Munster, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Cyteir Therapeutics, Inc.

Must not be taking: Antibiotics, Antifungals, Antivirals, Corticosteroids

Disqualifiers: HIV, Hepatitis, Stroke, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

169 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called CYT-0851 in patients with certain types of cancer that have not responded to other treatments. The goal is to see if the drug is safe and understand how it works in the body.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot be on certain medications like those that prolong the QTc interval or narrow therapeutic index drugs sensitive to CYP3A, P-gp, or BCRP without approval. There is also a 14-day washout period for some therapies.

What safety data exists for CYT-0851 and related treatments?

The research articles provided do not contain safety data specifically for CYT-0851 or the related treatments listed. ^{1 2 3 4 5}

Research Team

Markus Renschler, MD

Principal Investigator

Cyteir Therapeutics

Eligibility Criteria

Adults with certain B-cell malignancies or advanced solid tumors who understand the study and consent to participate. They must have a specific type of tumor, measurable disease, be in good physical condition (ECOG 0-1), and agree to use contraception if necessary. Excluded are those unable to swallow pills, recent heart attack or stroke victims, uncontrolled hypertension sufferers, individuals with active CNS metastases or significant health issues that could affect safety.

Inclusion Criteria

My cancer is a type of B cell malignancy confirmed by testing.

I can and agree to have a biopsy, or I can provide a recent sample if needed.

My recent tests show positive biomarkers.

Exclusion Criteria

I have not had a heart attack or stroke in the last 6 months.

I haven't had cancer treatment in the last 14 days.

I had hepatitis C but completed treatment and now have an undetectable viral load.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Dose Escalation

CYT-0851 administered orally in rising doses QD or BID for 28 day cycles

28 days per cycle

Treatment - Combination Therapy

CYT-0851 administered with various combinations: capecitabine, rituximab and bendamustine, or gemcitabine

21-28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• Bendamustine
• Capecitabine
• CYT-0851
• Gemcitabine
• Rituximab

Trial Overview The trial is testing CYT-0851 alone and combined with other chemotherapy drugs like rituximab and bendamustine or gemcitabine in patients with relapsed/refractory B-cell malignancies and advanced solid tumors. The goal is to determine safe dosages for Phase 2 trials.

Participant Groups

Group I: CYT-0851 dose expansion Experimental Treatment 1 Intervention

Part B: CYT-0851 administered orally at the selected Phase 2 dose for 28 day cycles

Group II: CYT-0851 dose escalation Experimental Treatment 1 Intervention

Part A: CYT-0851 administered orally in rising doses QD or BID for 28 day cycles

Group III: CYT-0851 and rituximab and bendamustine Experimental Treatment 2 Interventions

Part C: Daily oral doses of CYT-0851 for 28 days in combination with rituximab on Day 1 and bendamustine on Days 1 and 2 of each 28 day cycle

Group IV: CYT-0851 and gemcitabine Experimental Treatment 2 Interventions

Part D: Daily oral doses of CYT-0851 for 28 days in combination with gemcitabine on Day 1, 8 and 15 of each 28 day cycle

Group V: CYT-0851 and capecitabine Experimental Treatment 2 Interventions

Part E: Daily oral doses of CYT-0851 for 21 days in combination with capecitabine on Days to 14 of each 21 day cycle

Who Is Running the Clinical Trial?

Cyteir Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

170+

Findings from Research

In a study of 36 patients with advanced non-small cell lung cancer (NSCLC), the combination of irinotecan and cisplatin showed a partial response rate of 22.9% and a stable disease rate of 60%, indicating its efficacy in this patient population.

The treatment was associated with manageable adverse events, with grade III/IV side effects occurring in a minority of patients, including neutropenia (16.7%) and alopecia (13.9%), suggesting that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer]. Zhang, XR., Zhu, YZ., Xiu, QY., et al.[2018]

In a phase II study involving 70 patients with advanced non-small cell lung cancer (NSCLC), the combination of irinotecan (CPT-11) and cisplatin resulted in a promising objective response rate of 52%, with one complete response and 32 partial responses.

The treatment demonstrated a median survival time of 44 weeks and a 1-year survival rate of 33%, while the major toxicities included leucopenia and diarrhea, affecting a significant portion of patients but deemed acceptable in the context of the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group. Masuda, N., Fukuoka, M., Fujita, A., et al.[2019]

In a study of 400 high-risk stage III colon cancer patients receiving chemotherapy, those with the UGT1A1*28 homozygous mutation experienced significantly higher rates of severe hematologic toxicity (50%) compared to those with the UGT1A1*1 homozygous genotype (16.2%).

The -3156G>A UGT1A1 polymorphism was found to be a strong predictor of early severe hematologic toxicity, with a hazard ratio of 8.4 for patients with the A/A genotype compared to the G/G genotype, indicating the importance of genetic testing before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Côté, JF., Kirzin, S., Kramar, A., et al.[2018]

In a phase II study involving 45 patients with advanced colorectal cancer, the combination of oral S-1 and weekly irinotecan showed an overall response rate of 48.9%, indicating significant efficacy as a first-line treatment.

The treatment was well-tolerated, with manageable grade 3 or 4 toxicities, including neutropenia (8.9%) and diarrhea (6.7%), suggesting it may be a safer alternative compared to conventional chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer. Ogata, Y., Tanaka, T., Akagi, Y., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer]. [2018]

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

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group. [2019]

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

UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer]. [2018]

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

Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer. [2021]