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Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7Phase 1NCT03144778

Durvalumab With or Without Tremelimumab in Treating Participants With Stage II-IVA Oropharyngeal Squamous Cell Cancer

A Phase 1 study testing Durvalumab and Tremelimumab in people with Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 and Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies how well durvalumab with or without tremelimumab works in treating participants with stage II-IVA oropharyngeal squamous cell cancer. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab and Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
12 Jul 2017to 15 Mar 2021
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Written informed consent to participate in the study according to the investigational review board (IRB)
  • Suspected or histologically/cytologically confirmed oropharyngeal squamous cell carcinoma (OPSCC), stage II, III, or IVA (according to the American Joint Committee on Cancer [AJCC] 7th edition), or patients with loco-regional recurrence from an OPSCC primary, if time of recurrence is at least 6 months after completion of initial curative intent treatment (surgery or radiotherapy +/- chemotherapy or cetuximab). Patients with a suspected lesion may be enrolled and a baseline biopsy will be obtained as part of the study. If squamous cell histology is not confirmed, patients will be discontinued from the study
  • Patients must have surgically resectable disease in the opinion of the treating physician. For patients with a primary OPSCC, patients must be eligible for TORS (transoral robotic surgery)
  • Available tissue from prior biopsy (minimum of 10 unstained slides), or willing to undergo core biopsy to obtain tumor material. Biopsy will be mandatory for patients with recurrent disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Hemoglobin >= 9.0 g/dL
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  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
  • Platelet count >= 100 x 10^9/L (> 100,000 per mm^3)
  • Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). 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)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal
  • Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula
  • Patients with reproductive potential (e.g., females menopausal for less than 1 year and not surgically sterilized) must practice two highly effective contraceptive measures for the duration of study drug therapy and for at least 90 days after completion of durvalumab monotherapy or for at least 180 days after completion of durvalumab/tremelimumab combination therapy. Female patients of childbearing potential must provide a negative pregnancy test (urine) prior to treatment initiation
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up

Who cannot join

  • Histology other than squamous cell carcinoma
  • Primary site other than oropharynx
  • Prior systemic therapy (chemotherapy, biologic, or immunotherapy) for the same OPSCC. Prior chemotherapy, biologic therapy, and radiotherapy is allowed in patients with loco-regional recurrent disease, if administered at least 6 months prior to study enrolment
  • Previous treatment with Anti-CTLA-4 including tremelimumab or PD1/PD-L1 inhibitor, including durvalumab
  • History of another primary malignancy except for: (i) OPSCC with loco-regional recurrence after 6 months of curative-intent treatment and amenable to salvage surgery; (ii) malignancy treated with curative intent and with no evidence of active disease >= 2 years before the first dose of study drug and of low potential risk for recurrence; (iii) non-melanoma, skin cancer or lentigo maligna; in situ cervical, breast, prostate or bladder carcinoma
  • Any concurrent anticancer therapy
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  • Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from a baseline electrocardiogram using Fridericia's correction
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and single dose of dexamethasone of up to 20 mg (or equivalent corticosteroid) administered prior to diagnostic or baseline study biopsy of the oropharynx, as per institution standard of care
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or pneumonitis
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, seizures, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Known history of active tuberculosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
  • Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing two highly effective methods of birth control
  • Any medical or psychosocial condition that will interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Known allergy or hypersensitivity to investigational product (IP) or any excipient
  • Any unresolved grade 2 or higher toxicity from previous anti-cancer therapy
  • Primary tumor not amenable to TORS

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Checkpoint Inhibitors Assessment in Oropharynx Carcinoma (CIAO)

This phase I trial studies how well durvalumab with or without tremelimumab works in treating participants with stage II-IVA oropharyngeal squamous cell cancer. 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the differences between CD8+ tumor infiltrating lymphocytes evaluated by immunohistochemistry staining in the post-treatment surgical specimens as compared to baseline in patients treated with durvalumab single agent compared with patients receiving durvalumab plus tremelimumab.

SECONDARY OBJECTIVES:

  1. Safety and toxicity of durvalumab single agent or combined with tremelimumab administered every 4 weeks for 2 doses in the preoperative setting according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

II. Objective Response rate at 8 weeks, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

III. Percentage of patients undergoing the initially proposed surgery at 4 weeks.

IV. Percentage of patients undergoing the initially proposed surgery at 8 weeks.

  1. Percentage of viable tumor cells in the surgical specimen. VI. Patient-reported outcomes (PRO) during treatment with checkpoint inhibitors.

EXPLORATORY OBJECTIVES:

  1. To assess pre- and post- treatment tumor, blood and oral rinse based immune biomarkers.

II. Correlate tissue and blood-based biomarkers with human papillomavirus (HPV) status, outcomes and toxicity.

OUTLINE: Participants are randomized into 1 of 2 cohorts.

COHORT I: Participants receive durvalumab intravenously (IV) over 1 hour on days 1 and 29 in the absence of disease progression or unaccepted toxicity. Between days 52 and 72, participants undergo standard of care surgery.

COHORT II: Participants receive durvalumab IV over 1 hour and tremelimumab IV over 1 hour on days 1 and 29 in the absence of disease progression or unaccepted toxicity. Between days 52 and 72, participants undergo standard of care surgery.

After completion of study treatment, participants are followed up at 28 and 42 days, 4 and 6 months, and then periodically for up to 5 years.

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

  • TremelimumabBiological

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

    Given IV

Study groups in NCT03144778
Study groupRoleWhat they receive
Cohort I (durvalumab)ExperimentalParticipants receive durvalumab IV over 1 hour on days 1 and 29 in the absence of disease progression or unaccepted toxicity. Between days 52 and 72, participants undergo standard of care surgery.
Receives: Biological: Durvalumab
Cohort II (durvalumab, tremelimumab)ExperimentalParticipants receive durvalumab IV over 1 hour and tremelimumab IV over 1 hour on days 1 and 29 in the absence of disease progression or unaccepted toxicity. Between days 52 and 72, participants undergo standard of care surgery.
Receives: Biological: Durvalumab; Biological: Tremelimumab

What is being measured

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

  1. Change of CD8+ tumor infiltrating lymphocytes

    Change will be defined as the ratio of the CD8+ lymphocytes density in the post-treatment surgical specimens over the CD8+ density in the baseline biopsy before treatment.

    Measured: Before and after treatment, assessed up to 5 years

Secondary outcomes (4)

  1. Incidence of adverse events and serious adverse events

    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

    Measured: Up to 5 years

  2. Overall response rate

    Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.

    Measured: At 8 weeks

  3. Mean MD Anderson Symptom Inventory Head and Neck Cancer (MDASI-HN)

    The Mean MD Anderson Symptom Inventory Head and Neck Cancer (MDASI-HN) is a 28-item patient-reported outcomes questionnaire developed to measure severity or burden of systemic and head and neck squamous cell carcinoma (HNSCC)-specific symptoms and their interference with patients' daily functioning. Each symptoms is rated from 0 (not present) to 10 (as bad as you can imagine).

    Measured: At 29 Days

  4. Percentage of viable tumor cells in the surgical specimen

    Measured: Up to 5 years

Timeline

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

  1. First posted9 May 2017
  2. Study start12 Jul 2017
  3. Primary completion15 Mar 2021
  4. Study completion15 Mar 2021

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03144778
Sponsor's protocol ID
2016-0805
Other IDs
NCI-2018-01199, 2016-0805
Status last verified
Mar 2021
First submitted
5 May 2017
Last updated
18 Mar 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ferrarotto R, Bell D, Rubin ML, Hutcheson KA, Johnson JM, Goepfert RP, Phan J, Elamin YY, Torman DK, Warneke CL, Hessel AC, Garden AS, Myers JN, Johnson FM, Lee JJ, Sikora AG, Gillison ML, Glisson BS, Gross ND. Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results. Clin Cancer Res. 2020 Jul 1;26(13):3211-3219. doi: 10.1158/1078-0432.CCR-19-3977. Epub 2020 Apr 8.

    PubMed 32269052

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Durvalumab and Tremelimumab in people with Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 and Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7, run by M.D. Anderson Cancer Center 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 13 inclusion and 20 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: finished, as of the sponsor's last update on 18 Mar 2021. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Change of CD8+ tumor infiltrating lymphocytes (time frame: Before and after treatment, assessed up to 5 years). 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 NCT03144778, which also lists 1 linked publication.

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 18 Mar 2021.

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