UCDCC#270: Avelumab and Stereotactic Ablative Radiotherapy in Non-responding and Progressing NSCLC Patients

NCT03158883 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 1054028UCDCC#270
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot, single center, open-label study to examine the ORR, safety, and toxicity of avelumab in combination with SAR in non-responding and progressing NSCLC patients previously treated with a PD-1 Inhibitor.

Conditions

Metastatic Non-small Cell Lung Cancer (NSCLC)

Keywords

Avelumab; NSCLC; Stereotactic ablative radiotherapy (SAR)

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

  Up to 90 days after completion of study treatment

Secondary Outcomes (8)

• Overall Survival (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 90 days after completion of study treatment.

• Progression-Free Survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 90 days after completion of study treatment.

• Disease Control Rate (DCR)

  From date of randomization to end of study, assessed up to 90 days follow-up

• Duration of Stable Disease

  From date of randomization to end of study, assessed up to 90 days follow-up

• Duration of Overall Response

  From date of randomization to end of study, assessed up to 90 days follow-up

Study Arms (2)

Non-responders

EXPERIMENTAL

Patients who initially progress at first response assessment on a PD-1 inhibitor will be enrolled to the "non-responder" arm. * Avelumab: 10 mg/kg administered by IV infusion q2w (1 cycle = 14 \[±2\] days). * Stereotactic ablative radiotherapy (SAR): the prescription dose will be 50 Gy over 5 fractions of 10 Gy each on an every 2 day basis (i.e., 2-3 treatments per week, with a minimum of 40 hours and a maximum of 96 hours between treatments) and completed within 1.5-2 weeks. SAR treatment will not be repeated.

Drug: Avelumab; Radiation: Stereotactic ablative radiotherapy (SAR)

Progressors

EXPERIMENTAL

Patients who initially present with PR, CR, or SD to a PD-1 inhibitor but subsequently progress will be enrolled to the "progressor" arm. * Avelumab: 10 mg/kg administered by IV infusion q2w (1 cycle = 14 \[±2\] days). * Stereotactic ablative radiotherapy (SAR): the prescription dose will be 50 Gy over 5 fractions of 10 Gy each on an every 2 day basis (i.e., 2-3 treatments per week, with a minimum of 40 hours and a maximum of 96 hours between treatments) and completed within 1.5-2 weeks. SAR treatment will not be repeated.

Drug: Avelumab; Radiation: Stereotactic ablative radiotherapy (SAR)

Interventions

Avelumab DRUG

Avelumab: 10 mg/kg administered by IV infusion q2w (1 cycle = 14 \[±2\] days).

Also known as: anti-PD-L1 IgG1 monoclonal antibody

Non-responders; Progressors

Stereotactic ablative radiotherapy (SAR) RADIATION

SAR: the prescription dose will be 50 Gy over 5 fractions of 10 Gy each on an every 2 day basis (i.e., 2-3 treatments per week, with a minimum of 40 hours and a maximum of 96 hours between treatments) and completed within 1.5-2 weeks. SAR treatment will not be repeated.

Also known as: stereotactic body radiotherapy, SBRT, SAR

Non-responders; Progressors

Eligibility Criteria

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

You may qualify if:

• Signed informed consent.
• Ability to comply with the protocol.
• Adults \>18 years of age with histologically proven stage IV non-small cell lung cancer.
• At least two sites of measurable disease as defined by RECIST 1.1; one of which must be amenable to treatment with SAR and accessible for a mandatory pre-treatment biopsy and a post- treatment biopsy at physician discretion. If a pulmonary nodule is being considered for SAR it must range in size from 1-5 cm.
• Have provided written consent for protocol directed biopsies.
• Patients with treated supratentorial metastases are allowed if stable, the patient is off steroids or on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent) and no evidence of intracranial hemorrhage.
• Archival tumor sample available. A minimum of 10 unstained slides. No fine needle aspiration (FNAs) allowed or tumor tissue from bone.
• ECOG performance status score of 0 or 1 (Appendix 1).
• Life expectancy ≥ 3 months.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days of the first study treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
• Liver function tests meeting the following criteria: total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 × ULN (for subjects with documented metastatic disease to the liver).
• INR and aPTT \<1.5 × ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to randomization)
• Creatinine clearance \>30 mL/min by Cockcroft-Gault formula (or local institutional standard method).
• No history of severe hypersensitivity reactions to other mAbs.

You may not qualify if:

• No chemotherapy or radiotherapy within the past 28 days.
• Any number of prior treatments is allowed. Must have failed at least one treatment regimen for metastatic disease and must have failed platinum-based chemotherapy (including as treatment for localized disease) or be deemed ineligible for platinum-based therapy by the treating medical oncologist.
• Most recent prior regimen was a PD-1 inhibitor (nivolumab or pembrolizumab) with progression. Last dose must have been delivered within 90 days of enrollment.
• Highly effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1% per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment.
• Negative serum pregnancy test at screening for women of childbearing potential.
• Patients whose tumors contain activating EGFR mutations or ALK rearrangement should be excluded from this study, unless disease has progressed on all available, approved therapies targeting the EGFR mutation or ALK rearrangement.
• All subjects with brain metastases, except those meeting the following criteria:
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
• No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
• Subjects must be either off steroids or on a stable or decreasing dose of \<10mg daily prednisone (or equivalent)
• Leptomeningeal disease.
• Uncontrolled pleural or pericardial effusion or ascites that would require recurrent drainage.
• Uncontrolled tumor related pain.
• Uncontrolled hypercalcemia.
• Pregnant and lactating women.

Sponsors & Collaborators

• Megan Daly, MD: lead
• EMD Serono: collaborator

Study Sites (1)

UC Davis

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab; Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Megan Daly, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Two groups (n=13) of non-responders and progressors will go through the same treatment regime.

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 18, 2017
• Study Start: May 17, 2017
• Primary Completion: April 9, 2020
• Study Completion: June 24, 2020
• Last Updated: October 20, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)