What side effects are associated with this type of intervention?

Common cancer treatments, particularly those involving DNA-damaging agents like Temozolomide and enzyme inhibitors like M1774, are associated with a range of side effects. Temozolomide can cause nausea, vomiting, fatigue, and myelosuppression. Enzyme inhibitors often lead to gastrointestinal issues, fatigue, and liver enzyme abnormalities. Other frequent side effects across cancer therapies include neuropathy, hand-foot syndrome, and hematologic toxicities such as anemia, neutropenia, and thrombocytopenia.

What prior FDA approvals exist?

The FDA has approved several drugs for cancer treatment that function similarly to Temozolomide and M1774. Temozolomide, an alkylating agent, works by damaging the DNA of cancer cells, similar to other alkylating agents like cyclophosphamide and ifosfamide. Enzyme inhibitors, like M1774, include a range of targeted therapies such as PARP inhibitors (e.g., olaparib, rucaparib) which inhibit enzymes involved in DNA repair, and kinase inhibitors (e.g., imatinib, erlotinib) which block enzymes that promote cancer cell growth. These drugs represent a broad spectrum of FDA-approved treatments that either directly damage cancer cell DNA or inhibit critical enzymes necessary for cancer cell survival and proliferation.

What other types of research exist?

Promising alternatives to Temozolomide and M1774 for cancer treatment in 2024 include: 1) Pembrolizumab (PD-1 inhibitor) for its immunotherapy benefits, 2) Rucaparib and Niraparib (PARP inhibitors) for targeting DNA repair mechanisms, and 3) Tucatinib (HER2 inhibitor) for targeted therapy in HER2-positive cancers. These treatments have shown efficacy in various clinical trials and offer different mechanisms of action compared to Temozolomide and M1774.

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Alkylating agents

Temozolomide + Tuvusertib for Cancer

Phase 1 & 2

Recruiting

Led By Michael Cecchini

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of two drugs, temozolomide and M1774, in patients with advanced cancer that has spread. Temozolomide damages cancer cell DNA, while M1774 blocks growth enzymes. The goal is to find a more effective treatment for these patients.

Who is the study for?

Adults with advanced metastatic cancer, particularly colorectal cancer that's stable and has not spread widely after certain treatments. They must have tried all beneficial therapies or be unable to tolerate them. Those with specific blood levels, organ function, and no severe allergies to trial drugs can join. Pregnant women and individuals with uncontrolled illnesses or recent adverse reactions from past cancer treatments are excluded.

What is being tested?

The trial is testing the combination of Temozolomide (a DNA-damaging agent) and M1774 (an enzyme blocker) on patients with advanced cancers to see if this combo is safer or more effective than current treatments. It includes imaging tests like MRI/CT scans and biopsies for monitoring responses.

What are the potential side effects?

Potential side effects include damage to organs where enzymes are blocked by M1774, allergic reactions similar to those seen in other chemotherapy agents like dacarbazine, fatigue from anemia due to temozolomide, digestive issues affecting medication absorption, and possible heart rhythm problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose limiting toxicity and the maximum tolerated dose

Secondary study objectives

Objective response rate (ORR)

Overall survival (OS)

Progression free survival (PFS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (tuvusertib, temozolomide)Experimental Treatment6 Interventions

Patients receive tuvusertib PO QD) on days 1-7 and temozolomide PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and MRI as well as collection of blood samples throughout the trial. Patients also undergo a biopsy at baseline and may undergo one on study and/or at time of progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1090

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Temozolomide

2010

Completed Phase 3

~1880

Computed Tomography

2017

Completed Phase 2

~2740

Biospecimen Collection

2004

Completed Phase 3

~2020

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common cancer treatments often target the fundamental processes of cancer cell growth and survival. Temozolomide, a DNA-damaging agent, works by introducing alkyl groups to the DNA, leading to DNA strand breaks and ultimately cell death. This is particularly effective in rapidly dividing cancer cells that are less capable of repairing such damage. M1774, an enzyme inhibitor, blocks specific enzymes necessary for cancer cell growth and proliferation. By inhibiting these enzymes, M1774 can halt the progression of cancer cells. These mechanisms are crucial for cancer patients as they offer targeted approaches to disrupt cancer cell function, potentially leading to better treatment outcomes and fewer side effects compared to traditional chemotherapy.

Current strategies in treatment of oligodendroglioma: evolution of molecular signatures of response.