Berzosertib + Chemotherapy + Radiation for Head and Neck Cancer

Not currently recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, CYP3A4 inducers

Disqualifiers: Nasopharyngeal carcinoma, Brain metastases, others

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

Compensation: Varies

Number of Visits: 2

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for individuals with locally spread head and neck cancer. It examines the effects of berzosertib, a drug that may block cancer growth, in combination with chemotherapy (cisplatin) and radiation therapy. The trial aims to determine the optimal dose and assess how well these treatments work together. Suitable candidates have head and neck squamous cell cancer that cannot be surgically removed and do not have nasopharyngeal cancer or skin squamous cell carcinoma. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but it mentions avoiding strong inhibitors or inducers of CYP3A4, which could interact with the trial drug. It's important to discuss your current medications with the trial team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that berzosertib, when combined with other treatments, is generally well-tolerated by patients with advanced solid tumors. Studies report that patients taking berzosertib with gemcitabine experienced manageable side effects and showed early signs of treatment efficacy.

Cisplatin, a chemotherapy drug, is often used for head and neck cancers. Research indicates that weekly administration of cisplatin has similar safety outcomes compared to other schedules, with side effects remaining consistent regardless of frequency.

This trial is in an early stage and primarily aims to assess the safety of using berzosertib with cisplatin and radiation therapy. Early-phase trials like this one are designed to evaluate treatment safety and identify potential side effects. Since past studies have shown that berzosertib has manageable side effects, researchers expect similar results in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Berzosertib is unique because it targets the ATR kinase, a protein involved in DNA damage repair, enhancing the effectiveness of traditional treatments like chemotherapy and radiation. Unlike the standard cisplatin and radiation therapy for head and neck cancer, berzosertib is designed to make cancer cells more vulnerable to these treatments, potentially improving outcomes. Researchers are excited about this combination because it might lead to better tumor control and fewer side effects, offering hope for more effective and tolerable treatment options.

What evidence suggests that this treatment might be an effective treatment for head and neck cancer?

Research has shown that berzosertib, a drug in this trial, blocks enzymes that aid cancer cell growth. In lab studies, it performed well when combined with cisplatin and radiation. Participants in this trial will receive berzosertib alongside cisplatin and radiation therapy. Cisplatin, a chemotherapy drug, effectively treats head and neck cancers by killing cancer cells or stopping their spread. Radiation therapy, part of this treatment, uses high-energy rays to kill cancer cells and is a common and effective method for treating head and neck cancer. Together, these treatments may prove more effective for patients with locally advanced head and neck cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Taofeek K Owonikoko

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with locally advanced head and neck squamous cell carcinoma, not suitable for surgery, can join this trial. They must have a life expectancy over 3 months, measurable disease, normal organ function tests, and agree to use contraception. Excluded are those with certain other health conditions or treatments that could interfere with the study.

Inclusion Criteria

You have neck cancer where the original source is unknown, regardless of HPV/p16 status.

Patients must have histologically or cytologically confirmed head and neck squamous cell cancer (HNSCC) including paranasal sinus cancers but excluding nasopharyngeal carcinomas

Clinical staged III or IV HNSCC, according to American Joint Committee on Cancer (AJCC) 7th Edition, that is not amenable to surgical resection

Exclusion Criteria

You cannot be taking any other experimental drugs or treatments.

You have a medical condition that is not well controlled or managed.

You cannot participate if you have nasopharyngeal carcinoma, skin squamous cell carcinoma (SCC), or salivary gland carcinomas.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive berzosertib, cisplatin, and radiation therapy. Berzosertib is administered IV over 60 minutes on day -7 and then weekly on day 2, cisplatin IV over 30-60 minutes weekly on day 1, and radiation therapy once daily, 5 days a week.

7 weeks

Weekly visits for drug administration and daily visits for radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes imaging and assessment of metabolic response.

2 years

Every 2 weeks for 3 months, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Berzosertib (M6620)
• Cisplatin
• Radiation Therapy

Trial Overview The trial is testing Berzosertib combined with usual chemotherapy (Cisplatin) and radiation therapy in patients with advanced head and neck cancer. It aims to find the best dose of Berzosertib that's effective but also safe when used alongside standard treatments.

How Is the Trial Designed?

Group I: Treatment (berzosertib, cisplatin, radiation therapy) Experimental Treatment 7 Interventions

Patients receive berzosertib IV over 60 minutes on day -7 and then weekly on day 2 and cisplatin IV over 30-60 minutes weekly on day 1. Patients also undergo radiation therapy once daily, 5 days a week. Treatment continues for up to 7 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, PET/CT, or MRI throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. nature.com nature.com/articles/s41416-021-01405-x

Phase 1 study of the ATR inhibitor berzosertib (formerly ... Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02567422

Testing the Addition of M6620 (VX-970, Berzosertib) to ... Giving M6620 together with cisplatin and radiation therapy may work better in treating patients with locally advanced head and neck squamous cell carcinoma.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02631-X/fulltext

656MO Phase I study of M6620 (VX-970, berzosertib) in ... M6620 is a highly potent and selective ATP-competitive ATR inhibitor. It showed strong synergy with cisplatin and radiation in preclinical cancer models.

4. onclive.com onclive.com/view/berzosertib-plus-standard-chemoradiation-elicits-promising-responses-in-locally-advanced-hnscc

Berzosertib Plus Standard Chemoradiation Elicits ... We just saw the results [from a phase 2 study of xevinapant showing that] 3-year PFS and OS data were significantly improved. That improvement ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10663216/

The ATR inhibitor berzosertib acts as a radio The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines · Abstract · Introduction.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12278758/

Safety and Tolerability of Berzosertib, an Ataxia ... The addition of ATR inhibition to PARP inhibition results in mitotic lethality and an opportunity to further enhance cisplatin sensitivity.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8368196/

Phase 1 study of the ATR inhibitor berzosertib (formerly ... Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.