66 Participants Needed

M6620 + Irinotecan for Cancer

Recruiting at 23 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of M6620 and irinotecan hydrochloride in treating patients with solid tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). M6620 and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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 M6620 + Irinotecan for cancer?

Research shows that irinotecan, when combined with other drugs like bevacizumab, has been effective in treating various cancers, such as colorectal and ovarian cancer. This suggests that irinotecan can be a valuable part of cancer treatment regimens.12345

What safety information is available for the combination of M6620 and Irinotecan in cancer treatment?

Irinotecan, one of the drugs in this combination, has been associated with side effects like diarrhea and myelosuppression (a decrease in bone marrow activity leading to fewer blood cells). The maximum tolerated dose varies based on genetic factors, and dose-limiting toxicities include neutropenia (low white blood cell count) and diarrhea.678910

What makes the drug M6620 + Irinotecan unique for cancer treatment?

The combination of M6620 (Berzosertib) and Irinotecan is unique because M6620 is an ATR inhibitor, which may enhance the effectiveness of Irinotecan by interfering with cancer cells' ability to repair DNA damage, potentially making the cancer cells more susceptible to treatment.27111213

Research Team

Dept of Medicine | University of Pittsburgh

Liza C. Villaruz

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Eligibility Criteria

Adults with metastatic or inoperable solid tumors, including pancreatic, colorectal, and small cell lung cancer. Participants must have certain organ functions within normal limits and a life expectancy over 12 weeks. They should be willing to use contraception and undergo mandatory biopsies if in the expansion cohort.

Inclusion Criteria

You need to have a certain level of a type of white blood cell called neutrophils.
I have a known DNA repair issue or specific cancer types like pancreatic, colorectal, or small cell lung cancer.
Your white blood cell count is 3,000 or higher.
See 14 more

Exclusion Criteria

I am not taking strong medication that affects liver enzyme activity.
I don't have any severe illnesses that would stop me from following the study's requirements.
My HIV is not well-managed.
See 4 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Patients receive irinotecan hydrochloride IV over 90 minutes and M6620 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 12 cycles.

48 weeks
24 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months
3 visits (in-person)

Treatment Details

Interventions

  • Berzosertib
  • Irinotecan Hydrochloride
Trial OverviewThe trial is testing M6620 (berzosertib) combined with irinotecan hydrochloride to determine safe dosages and side effects. It targets patients whose tumors may not respond to standard treatments or for whom no standard treatment exists.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (irinotecan, M6620)Experimental Treatment5 Interventions
Patients receive irinotecan hydrochloride IV over 90 minutes and M6620 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood samples throughout the study and undergo CT at screening, throughout the study, and during follow up.

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a phase II study involving 77 previously untreated patients with metastatic colorectal cancer, the combination of capecitabine, irinotecan, and bevacizumab showed a promising progression-free survival rate of 61% at 9 months, with median overall survival of 24.8 months.
While 62% of patients experienced at least one severe adverse event, the regimen was generally well-tolerated, and quality of life remained stable throughout the treatment cycles.
Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study.Garcia-Alfonso, P., Chaves, M., Muñoz, A., et al.[2018]
The addition of bevacizumab to the VOIT regimen (vincristine, oral irinotecan, and temozolomide) in a pediatric trial showed some antitumor activity, particularly in patients with Ewing sarcoma, but the overall benefit of adding bevacizumab is still uncertain.
Reducing the dose of temozolomide from 150 mg/m² to 100 mg/m² improved the tolerability of the treatment, allowing more patients to complete the therapy without significant dose reductions due to side effects.
Pilot study of vincristine, oral irinotecan, and temozolomide (VOIT regimen) combined with bevacizumab in pediatric patients with recurrent solid tumors or brain tumors.Wagner, L., Turpin, B., Nagarajan, R., et al.[2020]
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.
Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers.Rosen, LS.[2018]

References

Low-dose-intensity bevacizumab with weekly irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. [2021]
Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study. [2018]
Bevacizumab with FOLFIRI or XELIRI in the First-line Therapy of Metastatic Colorectal Carcinoma: Results from Czech Observational Registry. [2015]
Bevacizumab added to the irinotecan and capecitabine combination for advanced colorectal cancer: a well-tolerated, active and convenient regimen. [2018]
Pilot study of vincristine, oral irinotecan, and temozolomide (VOIT regimen) combined with bevacizumab in pediatric patients with recurrent solid tumors or brain tumors. [2020]
Dysarthria induced by irinotecan in a patient with colorectal cancer. [2019]
Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. [2018]
Irinotecan and gemcitabine in patients with solid tumors: phase I trial. [2022]
Dose-finding study and pharmacogenomic analysis of fixed-rate infusion of gemcitabine, irinotecan and bevacizumab in pretreated metastatic colorectal cancer patients. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with Metastatic Colorectal Cancer. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Safety, pharmacokinetics, and activity of EZN-2208, a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies. [2022]
Registration-directed phase 1/2 trial of irinotecan for pediatric solid tumors. [2020]
Cetuximab and Irinotecan With or Without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial. [2022]