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

Stopped early · Phase 2

Conditions studied: NSCLC Stage IV, NSCLC, Recurrent

In brief

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.

Key facts

Study ID

NCT03713944

Run by

Nasser Hanna

People needed

30

Starts

2018-11-15

Expected to finish

2021-12-16

Last updated by the study team

2023-03-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 100 K/mm3
• Serum creatinine: ≤1.5 X upper limit of normal (ULN) OR Calculated Creatinine Clearance: ≥ 40 cc/min using the Cockcroft-Gault formula
• Bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 1.5 × ULN or < 5x ULN if the transferase elevation was due to liver metastases
• Alanine aminotransferase (ALT) ≤ 1.5 × ULN or <5x ULN if the transferase elevation was due to liver metastases
• International Normalized Ratio (INR) or Prothrombin Time (PT) \& aPTT ≤ 1.5 × ULN (unless subjects is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two non-hormonal methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for 5 months after the last dose of atezolizumab or 120 days after the last dose of any study drug, whichever is later;
• examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Must use "estrogen-free" hormonal method if this is chosen contraception method.

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.
• The patient had experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
• The patient had uncontrolled arterial hypertension ≥150 / ≥90 mm Hg despite standard medical management.
• The patient has had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
• Patients with ≥ 2 + protein on dipstick urinalysis. All patients with ≥ 2 + protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours to be eligible.
• Clear cavitation of pulmonary lesions seen on imaging.
• The patient had significant bleeding disorders, vasculitis, or experienced Grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to enrollment.
• History of GI perforation and/or fistulae within 6 months prior to enrollment.
• Evidence of tumor invading or abutting major blood vessels.
• The patient had a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
• Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

Where it is running

• University of Illinois Cancer Center — Chicago, Illinois, United States
• Indiana Univeristy Melvin and Bren Simon Cancer Center — Indianapolis, Indiana, United States
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States
• University of Virginia Health System — Charlottesville, Virginia, United States
• University of Wisconsin — Madison, Wisconsin, United States
• ProHealth Care — Waukesha, Wisconsin, United States

Full record on ClinicalTrials.gov

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