Carboplatin Plus Pemetrexed Plus Atezolizumab Plus Bevacizumab in Chemotherapy and Immunotherapy-naïve Patients With Stage IV Non-squamous Non-small Cell Lung Cancer

NCT03713944 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: BTCRC-LUN17-139
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

This is a multicenter single arm phase II clinical trial. All eligible patients will receive: Carboplatin (AUC 5) i.v. day 1 plus pemetrexed (500 mg/m2) i.v. day 1 plus atezolizumab 1200 mg i.v. day 1 plus bevacizumab 15 mg/kg i.v. day 1 every 3 weeks for up to 4 cycles. Patients with non-PD after 4 cycles will be permitted to continue with maintenance therapy with pemetrexed plus atezolizumab plus bevacizumab every 3 weeks until the time of disease progression or intolerable toxicities.

Conditions

NSCLC Stage IV; NSCLC, Recurrent

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression free survival (PFS) defined as the time from the initiation of treatment to the time when the criteria for disease progression is met as defined by RECIST v1.1 or death of any cause.Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  From C1D1 until progression or death up to maximum of 20 Months

Secondary Outcomes (4)

• Overall Response Rate

  From C1D1 until death or up to a maximum of 28 months.

• Disease Control Rate

  From C1D1 until death or up to a maximum of 28 months

• Overall Survival

  From C1D1 up to a maximum of 28 Months or until death

• Number of Participants With Adverse Events

  From C1D1 up to a maximum of 20 Months or until death

Study Arms (1)

Carboplatin, Pemetrexed, Atezolizumab plus Bevacizumab

EXPERIMENTAL

Carboplatin (AUC 5) i.v. day 1 plus pemetrexed (500 mg/m2) i.v. day 1 plus atezolizumab 1200 mg i.v. day 1 plus bevacizumab 15 mg/kg i.v. day 1 every 3 weeks for up to 4 cycles. Patients with non-PD after 4 cycles will be permitted to continue with maintenance therapy with pemetrexed plus atezolizumab plus bevacizumab every 3 weeks until the time of disease progression or intolerable toxicities.

Drug: Carboplatin; Drug: Pemetrexed; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Carboplatin DRUG

Carboplatin, AUC 5

Carboplatin, Pemetrexed, Atezolizumab plus Bevacizumab

Pemetrexed DRUG

Pemetrexed 500mg/m2

Carboplatin, Pemetrexed, Atezolizumab plus Bevacizumab

Atezolizumab DRUG

Atezolizumab 1200mg

Carboplatin, Pemetrexed, Atezolizumab plus Bevacizumab

Bevacizumab DRUG

Bevacizumab 15mg/kg

Carboplatin, Pemetrexed, Atezolizumab plus Bevacizumab

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 HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Must have life expectancy of \> 3 months at time of consent
• Histological or cytological confirmation of non-squamous NSCLC.
• Must have known PD-L1 status using the Dako 22C3 antibody (+ vs. -) OR must have at least 5 unstained slides to perform PD-L1 testing (results not required for eligibility). PD-L1 positive is defined as a tumor proportion score (TPS) ≥ 1%. PD-L1 negative is defined as a TPS \<1%.
• Patients with known targetable mutations in EGFR or BRAF or known translocations in ALK or ROS1 are eligible if they have received FDA approved targeted therapy first. A 1-week washout prior to enrollment is strongly encouraged (3 weeks preferred).
• Stage IV disease or recurrent disease
• Measurable disease according to RECIST v1.1 criteria within 28 days prior to registration with either PET/CT scan, CT scan of chest and abdomen, or CT chest including upper abdomen and adrenal glands which define stage IV disease.
• Patients who had disease progression greater than 1 year after completing prior adjuvant therapy for stage I - III are eligible as long as no systemic therapy was given for recurrence.
• No prior immunotherapy or antiangiogenic therapy.
• Prior platinum therapy or pemetrexed are permissible if previously given in the adjuvant setting for stage I-III disease and disease recurrence is \> 1 year from completion of therapy.
• If subject received major surgery or radiation therapy of \> 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
• Demonstrate adequate organ function as defined below, with all screening labs to be obtained within 28 days prior to registration
• Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3

You may not qualify if:

• Active infection requiring systemic therapy
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Active secondary cancers.
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. Brain imaging with either MRI or CT with contrast must be performed on all subjects at screening to evaluate for the presence of brain metastases. Patients with a history of treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• The patient has not received stereotactic radiotherapy within 14 days prior to initiation of study treatment or whole-brain radiotherapy within 21 days prior to initiation of study treatment
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease and off steroid therapy for at least 14 days. Anticonvulsant therapy at a stable dose is permitted.
• Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
• Major surgery within 3 weeks of the first dose of trial treatment.
• Completed palliative radiotherapy within 7 days of the first dose of trial treatment.
• The patient had a history of uncontrolled hereditary or acquired thrombotic disorder.
• Patients with a history of gross hemoptysis (defined as bright red blood or ≥1/2 teaspoon) within 2 months prior to enrollment.
• The patient had clinically relevant congestive heart failure (CHF; NYHA II-IV) or symptomatic or poorly controlled cardiac arrhythmia.

Sponsors & Collaborators

• Nasser Hanna: lead
• Genentech, Inc.: collaborator

Study Sites (7)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Indiana Univeristy Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

ProHealth Care

Waukesha, Wisconsin, 53188, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence

Interventions

Carboplatin; Pemetrexed; atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Nasser Hanna, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: Single Arm Therapeutic study using historical controls

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 22, 2018
• Study Start: November 15, 2018
• Primary Completion: December 16, 2021
• Study Completion: December 16, 2021
• Last Updated: March 1, 2023
• Results First Posted: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)