Adavosertib + Radiation for Esophageal Cancer

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Chemotherapy, Radiotherapy, Allergic reactions, others

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

Compensation: Varies

Number of Visits: 16

Duration: 3 weeks

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial investigates the side effects and best dose of adavosertib and how well it works when given in combination with radiation therapy in treating patients with esophageal or gastroesophageal junction cancer for which no treatment is currently available (incurable). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving adavosertib together with radiation therapy kill more tumor cells than radiation therapy alone in treating patients with esophageal and gastroesophageal junction cancer.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take medications that strongly affect the enzyme CYP3A4. It's important to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of the treatment Adavosertib + Radiation for Esophageal Cancer?

Research shows that intensity-modulated radiotherapy (IMRT), a type of radiation therapy, can improve the prognosis for patients with esophageal cancer. Additionally, combining chemotherapy with radiotherapy has been found to be more effective than radiotherapy alone for treating esophageal cancer. ^{1 2 3 4 5}

Is the combination of Adavosertib and radiation therapy generally safe for humans?

The combination of radiotherapy and immune checkpoint inhibitors (ICIs) for esophageal cancer has shown a synergistic effect and good outcomes, but a summary of the efficacy and toxicity of combined therapy is still lacking. Some studies have reported adverse effects like esophageal stricture when combining radiation with other treatments, but these were managed successfully with additional therapies. ^{6 7 8 9 10}

What makes the Adavosertib + Radiation treatment unique for esophageal cancer?

The combination of Adavosertib, a drug that may enhance the effects of radiation, with advanced radiation techniques like IMRT and IGRT, offers a potentially more targeted and effective approach for treating esophageal cancer compared to traditional chemotherapy and radiation methods. ^{3 5 6 11 12}

Research Team

Eric D. Miller

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Eligibility Criteria

Adults with inoperable esophageal or gastroesophageal junction cancer, including squamous cell or adenocarcinoma, that is not eligible for definitive chemoradiation. Participants must have proper liver and kidney function, no severe heart conditions, be able to swallow capsules, and have a life expectancy over 3 months. Pregnant women are excluded.

Inclusion Criteria

My recent ECG shows no significant heart issues.

I have another cancer type, but it won't affect this trial's treatment.

My hepatitis B is under control with treatment.

Exclusion Criteria

I don't have long QT syndrome, a history of Torsades de pointes, recent heart attack, or ventricular arrhythmias.

I've had radiation therapy in my chest or belly area that might overlap with new treatment areas.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo radiation therapy once daily 5 days per week for 3 weeks and receive adavosertib orally during weeks 1 and 3

3 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

1 visit at 3 weeks, every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Adavosertib
• Radiation Therapy

Trial Overview The trial tests the safety and optimal dosage of Adavosertib combined with radiation therapy on patients with incurable esophageal or gastroesophageal junction cancers. The goal is to see if this combination is more effective than radiation alone in stopping tumor growth.

Participant Groups

Group I: Treatment (radiation therapy, adavosertib) Experimental Treatment 2 Interventions

Patients undergo radiation therapy QD 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib PO QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in the absence of disease progression or unacceptable toxicity.

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 461 patients with stage IV esophageal cancer, those receiving concurrent chemoradiotherapy (CCRT) showed a significant improvement in disease control rates (81.6% vs. 64.5% for chemotherapy alone) and better progression-free survival (PFS) of 8.7 months compared to 7.3 months for chemotherapy alone.

Patients treated with CCRT also experienced a higher rate of improvement in dysphagia symptoms (78.5% vs. 61.5%), suggesting that adding radiotherapy may enhance quality of life alongside survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for esophageal squamous cell cancer patients presenting with oligometastases. Chen, Y., Cheng, X., Song, H., et al.[2022]

In a study of 45 patients with esophageal squamous cell carcinoma, simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) demonstrated promising overall survival rates of 42.2% and progression-free survival rates of 40.7% at 3 years, indicating its efficacy as a treatment option.

The treatment was associated with a low toxicity profile, as no patients experienced severe (grade 4-5) side effects, and the most common side effect, radiation esophagitis, was manageable, affecting 64% of patients but only 13% at grade 3 severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma: early results of a phase II study. Yu, WW., Zhu, ZF., Fu, XL., et al.[2021]

Ablative robotic stereotactic body radiosurgery (SBRT) was safely administered to 50 women with recurrent gynecologic cancers, with a 96% target response rate and a 68% clinical benefit observed at 6 months.

The treatment resulted in a median overall survival of 20.2 months, although a significant 62% of patients experienced non-radiosurgical disease relapse, indicating the need for further studies combining SBRT with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies. Kunos, CA., Brindle, J., Waggoner, S., et al.[2021]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Efficacy of the conservative treatment of patients with inoperable esophageal cancer]. [2013]

2. China pubmed.ncbi.nlm.nih.gov

Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for esophageal squamous cell cancer patients presenting with oligometastases. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Simultaneous Integrated Boost Intensity-Modulation Radiation Therapy Combined with Systematic and Standardized Management for Esophageal Cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Prognostic Factors for Patients with Esophageal Cancer Receiving Definitive Radiotherapy Alone: A Retrospective Analysis. [2022]

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

Concurrent chemoradiotherapy with raltitrexed and nedaplatin regimen for esophageal squamous cell carcinoma. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Esophageal Stricture Following Radiation, Concurrent Immunochemotherapy, Treated With Hyperbaric Oxygen and Dilation. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma: early results of a phase II study. [2021]

8. China pubmed.ncbi.nlm.nih.gov

Update of latest data for combined therapy for esophageal cancer using radiotherapy and immunotherapy: A focus on efficacy, safety, and biomarkers. [2023]

9. China pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of intensity-modulated radiotherapy on esophageal carcinoma]. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies. [2021]

11. Japan pubmed.ncbi.nlm.nih.gov

[Radiotherapy and chemotherapy of esophageal cancer]. [2006]

12. England pubmed.ncbi.nlm.nih.gov

Fractionated irradiation induced radio-resistant esophageal cancer EC109 cells seem to be more sensitive to chemotherapeutic drugs. [2021]