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Head and Neck CancerPhase 1/2PINCHNCT03829007

PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC

A Phase 1/2 study testing PD-L1 imaging and Durvalumab in people with Head and Neck Cancer, run by Radboud University Medical Center at 4 sites in Netherlands.

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

Non-invasive imaging of tumor PD-L1 expression with 89Zr-labeled durvalumab PET/CT predicts response to durvalumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
PD-L1 imaging and Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
4 sitesNetherlands
Study dates
15 Apr 2019to 9 Dec 2021
Phase
Phase 1/2
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 and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  • Age > 18 years at time of study entry, age > 20 years for Japanese subjects.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of > 12 weeks
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin≥ 9.0 mmol/L
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  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
  • Platelet count ≥ 100 x 109/L (>100,000 per mm3)
  • 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)
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
  • Serum creatinine CL>40 mL/min by MDRD
  • Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
  • 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.
  • Histological proven recurrent or metastatic squamous cell cancer of the head and neck
  • At least one lesion with a tumor size ≥1 cm

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study
  • Participation in another clinical study with an investigational product during the last 4 weeks
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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  • Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug 28 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C).
  • Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, 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
  • Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
  • 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)
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • History of hypersensitivity to durvalumab or any excipients
  • History of hypersensitivity to the combination or comparator agent (If applicable)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 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
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab
  • Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control: Female patient of child-bearing potential
  • Females of childbearing potential who are sexually active with a non sterilized male partner must use at least 1 highly effective method of contraception (Table 1) from the time of screening and must agree to continue using such precautions for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy (based on 5x the half-life of durvalumab or tremelimumab). Non-sterilized male partners of a female patient must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Female patients should also refrain from breastfeeding throughout this period.
  • Male patients with a female partner of childbearing potential. Non-sterilized males who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy. Not engaging in sexual activity is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male patients should refrain from sperm donation throughout this period.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.

Trial locations and contacts

4 sites in 1 country.

Netherlands4 sites

  • Amsterdam UMC

    Amsterdam

  • UMC Groningen

    Groningen

  • Leiden UMC

    Leiden

  • Radboudumc

    Nijmegen

Other trials in Netherlands

About this study

Official title: PINCH - PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC

Non-invasive imaging of tumor PD-L1 expression with 89Zr-labeled durvalumab PET/CT predicts response to durvalumab.

Read the detailed description

The programmed death 1 (PD1)/ programmed death ligand 1 (PD-L1) pathway plays an important role in regulating the T-cell anti tumor response. Blocking this interaction with the anti PD-L1 monoclonal antibody durvalumab has proven to be effective resulting in durable disease control rates. Currently, PD-L1 expression as determined by immune histochemistry (IH) is the best available biomarker for treatment response, but standardized scoring criteria are lacking and the risk for sampling errors exists. Molecular imaging using 89Zr-labeled antibodies may overcome these limitations, enabling the visualization of PD-L1 expression in primary and metastatic tumor lesions and providing information on the in vivo accessibility of the PD-L1 target following intravenous administration. Besides, a baseline FDG-PET scan will be performed.

Being tested
PD-L1 imaging, Durvalumab
Keywords
durvalumab, PD-L1 imaging
Medical subject headings
Head and Neck Neoplasms

What participants receive

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

  • PD-L1 imagingDiagnostic test

    Also called 89Zr-durvalumab PET/CT

    89Zr-durvalumab injection followed by a PET/CT scan 5 days after injection

  • DurvalumabDrug

    Durvalumab treatment is initiated after the PET/CT scan in a fixed dose of 1500 mg iv q4w

Study groups in NCT03829007
Study groupRoleWhat they receive
PD-L1 imagingExperimental89Zr-durvalumab iv injection followed by a PET/CT scan at day 5 after injection.
Receives: Diagnostic Test: PD-L1 imaging; Drug: Durvalumab

What is being measured

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

  1. Tumor uptake of 89Zr-durvalumab

    standardized uptake values (SUV) of 89Zr-durvalumab uptake in tumor lesions will be measured.

    Measured: 1 year

Secondary outcomes (2)

  1. To assess the potential of PD-L1 PET imaging to predict disease control rate of patients with recurrent or advanced head and neck cancer treated with durvalumab q4w 1500mg iv

    PD-L1 PET imaging performed with the optimal dose as assessed in part 1 of the study

    Measured: 1-2 year

  2. Correlation between tumor uptake of 89Zr-durvalumab and PD-L1 expression as determined immunohistochemically

    PD-L1 expression performed by Ventana SP263

    Measured: 1-2 years

Timeline

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

  1. First posted4 Feb 2019
  2. Study start15 Apr 2019
  3. Primary completion17 Dec 2020
  4. Study completion9 Dec 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 1/2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829007
Sponsor's protocol ID
PINCH
Acronym
PINCH
Status last verified
Jan 2022
First submitted
9 Jan 2019
Last updated
10 Jan 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PD-L1 imaging and Durvalumab in people with Head and Neck Cancer, run by Radboud University Medical Center at 4 sites in Netherlands.

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 15 inclusion and 27 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 10 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Netherlands. 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?

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?

Tumor uptake of 89Zr-durvalumab (time frame: 1 year). 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 NCT03829007.

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 10 Jan 2022.

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