A Pilot Study of MPDL3280A and HIGRT in Metastatic NSCLC

NCT02463994 | Completed Early Phase 1 DMC

• 2 other identifiers: UMCC 2015.005HUM00100387
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out whether a brief course of radiation therapy given to one area affected by the cancer will improve the chances of responding to immuno-therapy in the form of a medicine called MPDL3280A, an antibody against PD-L1. PD-L1 is expressed on lung cancers and is known to block the effects of the body's immune system in attacking the cancer. Blocking this PD-L1 has been shown to improve the body's immune cells to attack and kill the cancer cells in non-small cell lung cancer. The goal of this study is to see if prior treatment with radiation will allow improved recognition of the cancer by the body's immune cells in the presence of MPDL3280A.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The number of participants that respond to a combination of HIGRT and MPDL3280A (PD-L1)

  The primary outcome is overall response rate (ORR) to combination of HIGRT and MPDL3280A. The number of participants that respond to treatment will be determined. Response will be assessed by Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1, using primarily CT scans, immune response criteria and/or clinical benefit as assessed by the investigator.

  5 years

Study Arms (1)

MPDL3280A + HIGRT

EXPERIMENTAL

Drug: MPDL3280A; Radiation: Hypofractionated Radiotherapy

Interventions

MPDL3280A DRUG

Patients will receive 1,200 mg I.V. Q 3 weeks of MPDL3280A until progression.

MPDL3280A + HIGRT

Hypofractionated Radiotherapy RADIATION

Hypofractionated Image-Guided Radiotherapy (HIGRT)

MPDL3280A + HIGRT

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 Form (ICF)
• Ability and willingness to comply with the requirements of the study protocol
• Age ≥18 years old
• ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1 (scores run from 0 to 5 where 0 denotes perfect health and 5 death).
• Patients with ECOG PS of 2, secondary to the underlying disease, may be enrolled.
• Patients with Stage IIIB (not eligible for definitive chemo-radiotherapy), Stage IV, or recurrent non-small cell lung cancer (NSCLC); patients with Stage IV NSCLC should have previously received platinum based doublet chemotherapy. Patients with a new diagnosis of Stage IV NSCLC are eligible if they have an initial requirement for palliative XRT for symptomatic lesion (example: painful bone lesion or obstructive airway).
• Patients must be candidates for palliative radiation.
• Measurable disease per mRECIST v1.1 Patients must have at least 1 distinct site of measurable disease, ≥ 1 cm in its largest diameter, in addition to the site that is being irradiated.
• Patients may have additional measurable and/or non-measurable but radiographically visible metastatic lesions (e.g. bone metastases).

You may not qualify if:

• Patients must be candidates for PD-L1 Ab as determined by the treating physician
• At least 3 weeks must have elapsed from any prior chemotherapy, and the patient must have recovered from side effects to ≤ grade 1 toxicities.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
• ANC (Absolute Neutrophil Count) ≥ 1500 cells/µL
• WBC (White Blood Cell) counts \> 2500/µL
• Lymphocyte count ≥ 500/µL
• Platelet count ≥ 100,000/µL; for patients with hematologic malignancies, platelet count ≥ 75,000/µL
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x ULN with the following exception:
• Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
• AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) ≤ 3.0 x ULN with the following exception: Patients with liver involvement: AST and/or ALT ≤ 5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN with the following exception: Patients with documented liver involvement or bone metastases: alkaline phosphatase ≤ 5 x ULN
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in kg) x (0.85 if female) 72 x (serum creatinine in mg/dL)
• INR (International Normalized Ratio) and aPTT ≤1.5 x ULN
• This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low molecular weight heparin or warfarin) should be on a stable dose.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• University of Washington: collaborator

Study Sites (2)

The University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Washington, Seattle

Seattle, Washington, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Radiation Dose Hypofractionation

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)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Nithya Ramnath, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 29, 2015
• First Posted: June 8, 2015
• Study Start: October 1, 2015
• Primary Completion: November 7, 2018
• Study Completion: November 7, 2018
• Last Updated: February 8, 2019

Record last verified: 2019-02

Locations

US (2)