Decitabine + Durvalumab for Head and Neck Cancer

Overseen By Sara I Pai, MD, PHD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Organ transplant, Infections, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of drugs to help the immune system combat head and neck cancer that has returned or spread after standard treatments. The study tests a mix of immune-boosting drugs, including Durvalumab (an immunotherapy drug), and a DNA-targeting drug to determine if they can work together to slow or stop cancer growth. Individuals who experience cancer progression during or after specific immunotherapy treatments might be suitable candidates for this study. 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 novel combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 28 days before starting the trial, except for certain low-dose corticosteroids. It's best to discuss your current medications with the study team.

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

Research is investigating the safety and effectiveness of combining oral decitabine (ASTX727) with durvalumab for patients with certain types of head and neck cancer. Although the FDA has not approved durvalumab and tremelimumab for head and neck cancer, they have been tested for other conditions.

Durvalumab is approved for other cancer types, indicating a certain level of safety. Other studies have generally found it well-tolerated, with manageable side effects. Common side effects may include tiredness or skin reactions, while serious side effects are less common.

As this trial is in an early phase, researchers are closely monitoring the treatment's safety. This phase aims to determine the treatment's safety for people, so any side effects will be carefully observed.

In summary, while the treatment is not yet approved for head and neck cancer, previous research suggests it might be safe with manageable side effects. However, because this is an early-phase trial, the primary focus is on ensuring the treatment's safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they bring innovative approaches to fighting head and neck cancer. Oral Decitabine (ASTX727) is unique because it's taken by mouth, which can be more convenient compared to traditional intravenous chemotherapy. Additionally, the combination of decitabine with durvalumab, an immune checkpoint inhibitor, may enhance the body's immune response against cancer cells. The inclusion of 5' Azacitidine in another arm further explores different ways to boost immune responses, offering multiple avenues for potentially more effective treatment outcomes. These novel combinations and delivery methods could offer new hope for patients looking for alternatives to standard therapies like surgery, radiation, and chemotherapy.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that Oral Decitabine (ASTX 727) and Durvalumab, which participants in this trial may receive, may help treat head and neck cancer by strengthening the immune system against cancer cells. These drugs might work together to enhance the body's natural ability to fight cancer. Durvalumab, an immune checkpoint inhibitor, helps the immune system identify and attack cancer cells. Decitabine alters the DNA of cancer cells, making them easier for the immune system to detect. Early results suggest that this combination may benefit patients who have already tried other treatments, but further research is needed to confirm these findings. ^{1 5 6 7 8}

Who Is on the Research Team?

Sara Pai, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic squamous cell carcinoma of the head and neck, who have previously not responded to certain immune therapies. Participants must be in relatively good health with a life expectancy over 6 months, able to provide consent, and willing to use effective birth control methods.

Inclusion Criteria

My head or neck cancer has returned or spread and cannot be cured with treatment.

I am a man committed to not having children during the trial.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have had cancer spread to the lining of my brain and spinal cord.

I am not pregnant, breastfeeding, or if capable of having children, I am using effective birth control.

I do not have any unmanaged ongoing illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Oral decitabine is administered alone in Cycle 1, followed by combination therapy with durvalumab in Cycles 2-12

12 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Oral Decitabine (ASTX727)

Trial Overview The trial is testing oral Decitabine (ASTX727) combined with Durvalumab (MEDI4736) for their effectiveness and safety in treating head and neck cancer that has returned or spread. It's an early-phase study where all participants receive both drugs.

How Is the Trial Designed?

Group I: Oral Decitabine and Durvalumab Experimental Treatment 2 Interventions

Oral decitabine (ASTX 727) will be administered alone in Cycle 1 and the combination of oral decitabine and durvalumab therapy will be given in Cycles 2-12.

Group II: 5' Azacitidine 40 mg/m2 on Days 1-5, Durvalumab, and Tremelimumab Experimental Treatment 3 Interventions

5' Azacitidine will be administered alone in Cycle 1 and the combination of 5' Azacitidine, durvalumab, and tremelimumab therapy will be given in Cycles 2-12.

Group III: 5' Azacitidine 40 mg/m2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab Experimental Treatment 3 Interventions

5' Azacitidine will be administered alone in Cycle 1 and the combination of 5' Azacitidine, durvalumab, and tremelimumab therapy will be given in Cycles 2-12.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Astex Pharmaceuticals, Inc.

Industry Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03019003

Oral Decitabine (ASTX727) and Durvalumab in Recurrent ... The clinical trial is studying drugs that can boost the participant's immune system against the cancer cells as a possible treatment for head and neck cancer.

2. withpower.com withpower.com/trial/phase-2-head-and-neck-neoplasms-2-2017-e27f0

Decitabine + Durvalumab for Head and Neck Cancer This is a non-randomized, open-label, Phase Ib study to assess the safety and efficacy of a DNA methyltransferase inhibitor and immune checkpoint ...

3. clin.larvol.com clin.larvol.com/trial/NCT03019003

Oral Decitabine (ASTX727) and Durvalumab in Recurrent ... Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients. P1. Massachusetts General Hospital. N=13. Completed.

4. moffitt.org moffitt.org/clinical-trials-and-studies/clinical-trial-23777/

Clinical Trial 23777 Adding BMX-001 to usual symptom management may be more effective than usual symptom management alone at reducing oral mucositis in patients receiving ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399610/

Cancer Immunotherapy in Combination with Radiotherapy ... The improved efficacy observed in this trial may be attributed to the immunosuppressive effects of RT, which subsequently lead to increased PD‐1 ...

6. clinicaltrial.be clinicaltrial.be/fr/details/9393?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Oral Decitabine (ASTX727) and Durvalumab in Recurrent ... The FDA (the U.S. Food and Drug Administration) has not approved durvalumab (MEDI4736) or tremelimumab as a treatment for head and neck cancer.

7. app.trialscreen.org app.trialscreen.org/trials/phase-1-2-head-neck-cancer-oral-decitabine-astx727-durvalumab-recurrent-trial-nct03019003

Oral Decitabine (ASTX727) and Durvalumab in Recurrent ... The FDA (the U.S. Food and Drug Administration) has not approved durvalumab (MEDI4736) or tremelimumab as a treatment for head and neck cancer.

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/03/NCT03019003/Prot_SAP_000.pdf

Durvalumab (MEDI4736) Azacitidine/Decitabine (ASTX727) The safety and efficacy of oral decitabine (ASTX727) and durvalumab (MEDI4736) combination therapy are being evaluated in patients with recurrent or ...