PD-L1 ImagiNg to prediCt Durvalumab Treatment Response in HNSCC

NCT03829007 | Completed Phase 1

• 1 other identifier: PINCH
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Head and Neck Cancer

Keywords

durvalumab; PD-L1 imaging

Outcome Measures

Primary Outcomes (1)

• Tumor uptake of 89Zr-durvalumab

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

  1 year

Secondary Outcomes (2)

• 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

  1-2 year

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

  1-2 years

Study Arms (1)

PD-L1 imaging

EXPERIMENTAL

89Zr-durvalumab iv injection followed by a PET/CT scan at day 5 after injection.

Diagnostic Test: PD-L1 imaging; Drug: Durvalumab

Interventions

PD-L1 imaging DIAGNOSTIC_TEST

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

Also known as: 89Zr-durvalumab PET/CT

PD-L1 imaging

Durvalumab DRUG

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

PD-L1 imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• AstraZeneca: collaborator

Study Sites (4)

Amsterdam UMC

Amsterdam, Netherlands

Location

UMC Groningen

Groningen, Netherlands

Location

Leiden UMC

Leiden, Netherlands

Location

Radboudumc

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• carla van Herpen, Prof

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: February 4, 2019
• Study Start: April 15, 2019
• Primary Completion: December 17, 2020
• Study Completion: December 9, 2021
• Last Updated: January 10, 2022

Record last verified: 2022-01

Locations

NL (4)