Berzosertib + Irinotecan for Gastric Cancer

Recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Early stage cancer, Brain metastases, Allergic reactions, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Up to 1 year

14 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it advises avoiding certain drugs that interact with the trial medications. You should discuss your current medications with the study team to ensure there are no interactions.

What data supports the effectiveness of the drug combination Berzosertib and Irinotecan for gastric cancer?

Research shows that Irinotecan, when combined with other drugs like S-1 or cisplatin, has shown some effectiveness in treating advanced gastric cancer, with response rates ranging from 16.1% to 23.3% and a high tumor control rate. This suggests potential for Irinotecan in combination therapies, although specific data on Berzosertib is not provided. ^{1 2 3 4 5}

Is the combination of Berzosertib and Irinotecan safe for humans?

Irinotecan has been studied in various cancers, including gastric cancer, and common side effects include low white blood cell counts, diarrhea, and nausea, which are generally reversible. While specific safety data for the combination of Berzosertib and Irinotecan is not provided, Irinotecan alone has shown manageable side effects in clinical trials. ^{1 2 5 6 7}

What makes the drug combination of Berzosertib and Irinotecan unique for treating gastric cancer?

The combination of Berzosertib and Irinotecan for gastric cancer is unique because Berzosertib is a novel drug that targets the ATR (ataxia telangiectasia and Rad3-related) pathway, potentially enhancing the effectiveness of Irinotecan, which is already used in various combinations for gastric cancer. This approach may offer a new mechanism of action compared to existing treatments. ^{1 3 4 8 9}

What is the purpose of this trial?

This trial tests a combination of berzosertib and irinotecan in patients with advanced gastric or gastroesophageal junction cancer. Berzosertib blocks enzymes needed for cancer growth, and irinotecan kills or stops the spread of cancer cells. Irinotecan has been used in various combinations for treating advanced gastric and gastroesophageal cancers, showing some efficacy but not proving superior to other treatments. The goal is to find a more effective treatment for these difficult-to-treat cancers.

Research Team

Jordan D Berlin

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

This trial is for adults over 18 with progressive, metastatic, or unresectable gastric or gastroesophageal junction cancer that has a TP53 mutation. Participants must have tried at least two systemic therapies and meet certain health criteria (like blood cell counts). Women of childbearing age and men with partners of childbearing age must use contraception.

Inclusion Criteria

Leukocytes >= 3,000/mcL.

Absolute neutrophil count >= 1,500/mcL.

Hemoglobin >= 9 g/dL.

Exclusion Criteria

I do not have untreated or symptomatic brain metastases.

I haven't had any cancer besides local ones in the past 3 years.

I still have side effects from cancer treatment that are not hair loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive irinotecan IV over 90 minutes and berzosertib IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 2 months for up to 1 year.

1 year

Follow-up visits every 2 months

Treatment Details

Interventions

• Berzosertib
• Irinotecan

Trial Overview The trial is testing the effectiveness of combining berzosertib, which blocks enzymes needed for tumor growth, with irinotecan, a chemotherapy drug that kills or stops the spread of cancer cells. The goal is to see if this combination works better than irinotecan alone in treating these cancers.

Participant Groups

Group I: Treatment (irinotecan and M6620) Experimental Treatment 5 Interventions

Patients receive irinotecan IV over 90 minutes and berzosertib IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo endoscopic or CT assisted biopsy and MRI on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 23 patients with advanced gastric cancer, the combination therapy of irinotecan (CPT-11) and S-1 resulted in a promising overall response rate of 47.8% and a median time to progression of 210 days.

The treatment was associated with low rates of severe toxicity, with only 17.4% experiencing grade 3 or 4 hematological issues and 8.7% facing non-hematological toxicity, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of a combination of irinotecan and S-1 in patients with advanced gastric cancer (OGSG0002). Uedo, N., Narahara, H., Ishihara, R., et al.[2018]

The maximum-tolerated dose (MTD) of irinotecan (CPT-11) combined with cisplatin for treating advanced gastric cancer was determined to be 80 mg/m2, with neutropenia identified as the primary dose-limiting toxicity.

The treatment regimen resulted in a partial response in 10 out of 24 patients, leading to an overall response rate of 41.7%, indicating that this combination therapy is effective and warrants further investigation in phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. Shirao, K., Shimada, Y., Kondo, H., et al.[2018]

In a late phase II study involving 81 patients with advanced gastric cancer, irinotecan hydrochloride (CPT-11) demonstrated an overall response rate of 23.3% among evaluable cases, indicating its potential efficacy in this patient population.

The treatment was associated with significant toxicities, including leukopenia (41.2%) and anemia (28.9%), but these were generally reversible, suggesting that while CPT-11 is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. Futatsuki, K., Wakui, A., Nakao, I., et al.[2018]

Irinotecan (CPT-11) has demonstrated a broad range of antitumor activity across various cancer types, including lymphoma, leukemia, and several solid tumors, although most studies have focused on colorectal and gastrointestinal cancers.

Preliminary results indicate that irinotecan shows modest but reproducible activity in multiple cancers, suggesting the need for further well-designed clinical trials to better understand its efficacy and optimal use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. Rosen, LS.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of irinotecan (CPT-11) and S-1 in the treatment of advanced gastric cancer. [2018]

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

Phase II study of a combination of irinotecan and S-1 in patients with advanced gastric cancer (OGSG0002). [2018]

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

Irinotecan and paclitaxel in metastatic adenocarcinoma of the esophagus and gastric cardia. [2018]

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

Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[Late phase II study of irinotecan hydrochloride (CPT-11) in advanced gastric cancer. CPT-11 Gastrointestinal Cancer Study Group]. [2018]

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

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. [2018]

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

Dose-finding study and pharmacogenomic analysis of fixed-rate infusion of gemcitabine, irinotecan and bevacizumab in pretreated metastatic colorectal cancer patients. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

Activity and safety of a low dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin for relapsed gastric cancer patients: a preliminary report. [2019]

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

Irinotecan and cisplatin in advanced gastric or gastroesophageal junction carcinoma. [2018]