PD-L1 Imaging in Non Small Cell Lung Cancer' (PINNACLE)

NCT03514719 | Completed Phase 1

• 1 other identifier: MS100070_0167
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

In this feasibility study, a zirconium-89 (89Zr)-avelumab positron emission tomography (PET) scan will be performed in 37 patients prior to treatment with avelumab to:

1. 1.assess the tumor and systemic tissue uptake 89Zr-avelumab
2. 2.assess the potential to predict avelumab treatment response

Conditions

Non Small Cell Lung Cancer

Keywords

89Zr-avelumab PET; avelumab

Outcome Measures

Primary Outcomes (1)

• Tumor uptake of 89Zr-Avelumab

  Standardized uptake values (SUV) of 89Zr-Avelumab uptake in tumor lesions will be measured

  1 year

Secondary Outcomes (4)

• Correlation 89Zr-Avelumab uptake in tumor lesions and PD-L1 expression as determined by immunohistochemistry

  1-2 year

• Correlation between 89Zr-Avelumab uptake in tumor lesions and response to (neo)-adjuvant avelumab treatment

  1-2 years

• The number of treatment delays in surgical resections

  1-2 years

• Asses post-operative complications

  1-2 years

Study Arms (1)

89Zr-avelumab PET

EXPERIMENTAL

89Zr-avelumab injection followed by 89Zr-avelumab PET

Diagnostic Test: 89Zr-avelumab PET; Drug: Avelumab

Interventions

89Zr-avelumab PET DIAGNOSTIC_TEST

89Zr-avelumab injection followed by 89Zr-Avelumab PET scan

Also known as: ImmunoPET

89Zr-avelumab PET

Avelumab DRUG

Early stage disease (stage Ia (≥T1b tumor)-IIIa: neo-adjuvant avelumab treatment (10mg/kg iv q2w) for a maximum duration of 2 cycles after PET-imaging, followed by surgical resection of the tumor with curative intent Stage IIIb-IV disease: systemic treatment with avelumab 10mg/kg iv q2w after PET-imaging

89Zr-avelumab PET

Eligibility Criteria

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

You may qualify if:

• Male or female subjects aged ≥ 18 years, and \>50 years in patients with resectable stage Ia (≥T1b tumor) - IIIa NSCLC)
• Histological or cytologic proven stage IIIb/IV NSCLC or resectable stage Ia (≥T1b tumor) - IIIa NSCLC, where no pathological evaluation of mediastinal lymph nodes by mediastinoscopy is indicated according to the multidisciplinary tumor board
• ECOG performance score (0-1)
• At least one lesion with a tumour size ≥ 1 cm
• Haematologic function: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and haemoglobin ≥ 9 g/dL (may have been transfused)
• Hepatic function: total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
• Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• Highly effective contraception for both male and female subjects throughout the study and for at least after avelumab treatment administration intrinsic factor the risk of conception exists
• Fit for surgery (for patients with resectable stage Ia-IIIa disease), as assessed by treating thoracic surgeon / anesthesiologists based on sufficient cardiopulmonary status and absence of major contra-indications for surgery according to local guidelines

You may not qualify if:

• Immunosuppressants: "Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (eg, intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)."
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Prior organ transplantation, including allogeneic stem cell transplantation
• Infections: active infection requiring systemic therapy
• HIV/AIDS: known history for testing positive to an HIV test or known acquired immunodeficiency syndrome (AIDS)
• Hepatitis: hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or confirmatory HCV RNA if anti-HCV antibody screening test positive)
• Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
• Hypersensitivity to study drug: "Known prior severe hypersensitivity reactions to investigational product or any component in its formulations, including known severe hypersensitivity reactions to antibodies (Grade ≥ 3 NCI CTCAE v 4.03)
• Cardiovascular disease: "Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."8. Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable
• Other persisting toxicities: Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 \> 1); however, alopecia, sensory neuropathy Grade
• ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Radboud University

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• C.M.L. van Herpen, Prof.dr.

  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

Model Details: Patients with early stage disease (stage Ia(≥T1b)-IIIa) undergo pre-treatment PET-imaging and 2 cycles of neo-adjuvant avelumab treatment. Followed by surgical resection of the tumor. Patients with stage IIIb-IV NSCLC will undergo pre-treatment PET-imaging in only part 1 of the study, and receive avelumab treatment 10mg/kg q2w until disease progression or treatment toxicity

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 2, 2018
• Study Start: October 1, 2018
• Primary Completion: September 15, 2021
• Study Completion: December 2, 2021
• Last Updated: January 10, 2022

Record last verified: 2022-01

Locations

NL (1)