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Metastatic Head and Neck Squamous Cell CarcinomaPhase 1/2NCT03522584

Durvalumab, Tremelimumab and Hypofractionated Radiation Therapy in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

A Phase 1/2 study testing Durvalumab, Laboratory Biomarker Analysis and Stereotactic Body Radiation Therapy in people with Metastatic Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by University of Washington at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the side effects of durvalumab, tremelimumab and hypofractionated radiation therapy in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab, Laboratory Biomarker Analysis and Stereotactic Body Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
17 May 2018to 19 Jan 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven recurrent/metastatic squamous cell carcinoma arising from a previous head and neck primary site, and located within the head and neck region, lung mediastinum, lymph nodes, soft tissue metastases or bone, and who are not candidates for curative intent therapy
  • An actual body weight > 40kg
  • Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy
  • Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting, and including a platinum containing regimen)
  • Have received an anti-PD1 or anti PDL1 monoclonal antibody
  • Have a target lesion/s deemed suitable by the treating physicians for hypofractionated radiation therapy (HIGRT or SBRT) with the intent of palliation or prevention of symptoms; this lesion must be: a) 1-3 non overlapping sites in the head and neck region OR b) metastatic lesions outside the head and neck (H\&N) region in the lung mediastinum, soft tissue metastases, lymph nodes or bone (a minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no significant overlap between the lesions; patients should have RECIST 1.1 criteria measurable disease in addition to the lesion/s treated with radiation; if the site/s of radiation were previously radiated to high dose RT (> 50 Gy), there should be > 6 month time interval between the last dose of radiation and the start of radiation
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  • Have the ability to tolerate required radiotherapy-related procedures (e.g.: lie flat and hold position for treatment) as determined by the treating physician
  • Be willing and able to provide written informed consent for the trial and comply with the study visit requirements
  • Have measurable disease based on RECIST 1.1. (in addition to the lesion/s that will be treated with hypofractionated radiation therapy)
  • Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Hemoglobin >= 9.0 g/dL (should be performed within 10 days of treatment initiation)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (>= 1500 per mm^3) (should be performed within 10 days of treatment initiation)
  • Platelet count >= 100 x 10^9/L (>= 100,000 per mm^3) (should be performed within 10 days of treatment initiation)
  • Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) (should be performed within 10 days of treatment initiation); this will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =< 5 x ULN (should be performed within 10 days of treatment initiation)
  • Serum creatinine clearance (CL) > 60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (should be performed within 10 days of treatment initiation)
  • Evidence of post-menopausal status OR negative urinary or serum pregnancy test for female pre-menopausal patients; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:
  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy, or hysterectomy)
  • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential should be willing to use 1 method of highly effective birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy
  • Patient is >= 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention

Who cannot join

  • Has a body weight =< 40kg at the time of enrollment
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
  • Has a target lesion/s for radiotherapy that is > 5 cm (> 50 cc) in greatest dimension
  • Has a target lesion/s in a region that previously received high dose radiation therapy (RT) (> 50 Gy) demonstrating any of the following:
  • carotid artery encasement (> 180 degrees)
  • unprotected carotid artery (i.e. skin is directly over the carotid without intervening soft tissue, especially after prior neck dissection without a vascularized free flap) (a\&b due to risk of carotid blow out)
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  • skin infiltration by tumor (due to risk of fistula)
  • located in the larynx/hypopharynx primaries (due airway threat)
  • treated with high dose radiation therapy (> 50 Gy) within 6 months or less of trial enrollment
  • Any prior grade >= 3 immune-related adverse event (irAE) while receiving a prior immunotherapy agent, or any unresolved irAE > grade 1
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab; the following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
  • Has received a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
  • Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • Has known brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases; and stable and off steroids for at least 14 days prior to start of study treatment); following radiotherapy and/or surgery of the brain metastases patients must wait 4 weeks following the intervention and before initiating study treatment with imaging to confirm stability
  • Has an active autoimmune disease requiring systemic treatment within the past 2 years or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement will not be excluded from the study
  • Has evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring oral or intravenous glucocorticoids
  • Has an active infection requiring systemic therapy
  • Requires therapeutic anticoagulation or has known active bleeding diathesis
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 180 days after the last dose of trial treatment
  • Has received prior therapy with an anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has evidence of acute or chronic hepatitis B or hepatitis C
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • Has a mean QT interval corrected for heart rate (QTc) >= 470ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
  • Has a history of primary immunodeficiency or an allogeneic organ transplant
  • Has a history of hypersensitivity to durvalumab or tremelimumab excipient
  • Known history of previous clinical diagnosis of tuberculosis
  • Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, seizures

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Durvalumab (MEDI4736), Tremelimumab and Palliative Hypofractionated Image Guided Radiation Therapy (HIGRT) in Patients With Recurrent/Metastatic Squamous Cell Carcinomas of the Head and Neck Previously Treated With Immune Checkpoint Inhibitors

This phase I/II trial studies the side effects of durvalumab, tremelimumab and hypofractionated radiation therapy in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving durvalumab, tremelimumab, and hypofractionated radiation therapy may work better in treating patients with recurrent or metastatic head and neck squamous cell carcinoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To demonstrate safety and tolerability of durvalumab and tremelimumab and palliative radiation therapy in patients with recurrent metastatic squamous cell carcinomas of the head and neck previously exposed to an anti PD-1 or PDL-1 monoclonal antibody.

SECONDARY OBJECTIVES:

  1. Measure objective response rates based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. criteria in patients receiving the durvalumab, tremelimumab and palliative radiation therapy (RT) combination.

II. Determine overall and progression free survival in patients enrolled in the study.

OUTLINE:

Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1, week 1. Treatment repeats every 4 weeks for up to 4 cycles or every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes on day 1, week 16. Treatment repeats every 4 weeks for up to 9 cycles or every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo hypofractionated radiation therapy using either hypofractionated, image-guided radiotherapy (HIGRT) or stereotactic body radiation therapy (SBRT) over 3 fractions every other day (QOD) during week 3.

After completion of study treatment, patients are followed up at 30 days, 2, 3, 4, 6, 8, and 10 months, and then every 12 months.

Being tested
Durvalumab, Laboratory Biomarker Analysis, Stereotactic Body Radiation Therapy, Tremelimumab, Hypofractionated Image-Guided Radiation Therapy
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Stereotactic Body Radiation TherapyRadiation

    Also called SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

    Undergo SBRT

  • TremelimumabBiological

    Also called Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206

    Given IV

  • Hypofractionated Image-Guided Radiation TherapyProcedure or surgery

    Also called Hypofractionated Image-Guided Radiotherapy

    Undergo HIGRT

Study groups in NCT03522584
Study groupRoleWhat they receive
Treatment (tremelimumab, durvalumab, HIGRT, SBRT)ExperimentalPatients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1, week 1. Treatment repeats every 4 weeks for up to 4 cycles or every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes on day 1, week 16. Treatment repeats every 4 weeks for up to 9 cycles or every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo hypofractionated radiation therapy using either HIGRT or SBRT over 3 fractions QOD during week 3.
Receives: Biological: Durvalumab; Other: Laboratory Biomarker Analysis; Radiation: Stereotactic Body Radiation Therapy; Biological: Tremelimumab; Procedure: Hypofractionated Image-Guided Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Adverse Effects Graded According to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0

    Toxicities will be summarized as the number and percentage of patients with each type of toxicity, per Criteria for Adverse Events version 4.0

    Measured: From the start of study treatment up to 3 months after last study treatment, up to 38 months

Secondary outcomes (3)

  1. Response Rate

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 2 years

  2. Progression-free Survival

    Survival estimates will be calculated using the Kaplan-Meier method. Progression free survival is measured in months. PFS is defined as the amount of time between treatment initiation and when the disease progresses per RECIST 1.1 criteria

    Measured: From the date of study enrollment for up to 2 years

  3. Overall Survival

    Survival estimates will be calculated using the Kaplan-Meier method. Overall survival is measured in months. OS is defined as the amount of time between treatment initiation and when the patient is deceased.

    Measured: From the date of study enrollment for up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2018
  2. Study start17 May 2018
  3. Primary completion16 Dec 2021
  4. Study completion19 Jan 2022

Why it stopped: Terminated by the sponsor due to lack of efficacy in study treatment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03522584
Sponsor's protocol ID
9881
Other IDs
NCI-2018-00540, 9881, P30CA015704, RG1717067
Status last verified
Jun 2023
First submitted
30 Apr 2018
Last updated
12 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Durvalumab, Laboratory Biomarker Analysis and Stereotactic Body Radiation Therapy in people with Metastatic Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Adverse Effects Graded According to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 (time frame: From the start of study treatment up to 3 months after last study treatment, up to 38 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03522584.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.

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