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Non-Small Cell Carcinoma of Lung, TNM Stage 4Phase 2NCT03786692

Phase II Randomized Trial of Carboplatin+Pemetrexed+Bevacizumab+/- Atezolizumab in Stage IV NSCLC

A Phase 2 study testing Arm A and Arm B in people with Non-Small Cell Carcinoma of Lung, TNM Stage 4, run by Fox Chase Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

While cigarette smoking remains the primary cause of most lung cancer cases, lung carcinoma in never smokers account for nearly 20 percent of cases. Never smokers with lung cancer typically present with different molecular profiles from that of smokers, which results in prognostic and therapeutic implications. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Arm A and Arm B
Could I receive a placebo?
No, everyone receives an active treatment
How many people
107 participants
Where
1 siteUnited States
Study dates
4 Sep 2019to Jan 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must have histologically or cytologically confirmed stage IV non-squamous non-small cell lung cancer
  • Must have either tumors that harbor an EGFR mutation in exon 19 or exon 21, or must be never smoker wild-types. Never smoker wild-types are defined as patients with tumors without an ALK or ROS1 rearrangement, and are not harboring any EGFR mutation (this includes exons 19 or 21, exon 20, and any other rare EGFR mutations). Never smoker wild-type patients must have smoked less than 100 cigarettes in a lifetime. Patients with an EGFR mutation in exon 19 or 21 may be included irrespective of their smoking history. If a patient whose tumor originally had an exon 19 or 21 mutation develops a secondary activating or sensitizing mutation in exon 18-21 as a result of resistance to EGFR TKI therapy, then that patient is eligible. If tissue-based testing for EGFR mutation status is not available, blood-based EGFR testing that confirms presence of a mutation in exon 19 or 21 is acceptable, and these patients may be included in the stud
  • Must have measurable disease by CT or MRI, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v 1.1
  • Tumors that harbor an EGFR exon 19 or exon 21 mutation must have received prior treatments with one or more TKIs. A minimum washout period of 3 days is required to begin treatment in this trial. Patients who are never smoker wild-types must be treatment naïve
  • Must be chemotherapy, anti-VEGF therapy alone, and immunotherapy naive, with the exception of prior oral TKIs which are required for EGFR mutated patients. Patients who have received prior anti-VEGF therapy in combination with a TKI for advanced stage EGFR-mutated disease may be included. The number of prior oral TKIs and duration of use is neither specified nor limited.
  • History of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
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  • No ongoing requirement for corticosteroids as therapy for CNS disease
  • No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
  • No clinical evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
  • New asymptomatic CNS metastases detected at the screening scan must be ≤1 cm in size with no prior radiation therapy. These patients may then be eligible without the need for an additional brain scan prior to randomization, if all other criteria are met
  • May have received curative intent therapy (adjuvant therapy or therapy for locally advanced NSCLC), if this therapy was completed greater than 1 year from entry into the trial
  • Age > 18 years
  • ECOG performance status of 0 or 1
  • Must have normal organ and marrow function as defined below. The use of G-CSF should follow standard recommendations and physician discretion. If blood transfusion is performed for achieving hemoglobin levels, the levels should stay at ≥ 9.0 mg/ml for at least a week after transfusion.
  • Absolute neutrophil count > 1,500/mcL Hemoglobin ≥ 9.0 mg/ml Platelets > 100,000/mcL Total bilirubin ≤1.5 X institutional upper limit of normal (ULN) AST/ALT (SGOT/SGPT) < 3 times institutional normal limits, or up to 5 times institutional normal limits if the patient has liver metastases Creatinine OR Creatinine clearance ≤1.5 X ULN, OR > 40 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal as per Cockcroft-Gault formula International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) <1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Thyroid stimulating hormone (TSH) Within normal limits a
  • a: If TSH is not within normal limits at baseline, the subject will still be eligible if total T3 or free T4 are within normal limits.
  • Full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0. For heparin and LMWH there should be no clinically significant active bleeding (with no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
  • Ability to understand and willingness to sign a written informed consent and HIPAA consent document.
  • A biopsy, either core, cell block from FNA or cell block from surgical resection, must be available for the study. If the sample is not adequate, the patient must agree to provide a fresh biopsy specimen before the start of treatment. Any available archival tissue will also be collected. While a biopsy sample must be adequate and available for the study, an inadequate tissue sample would not be explicitly exclusionary and further discussion with the sponsor is allowed to assess the eligibility of the patient for the trial if, for clinical or other reasons, a new biopsy sample cannot be obtained.
  • Urinary protein must be ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24 hour urine collection for protein must demonstrate <1000 mg of protein in 24 hours to allow participation in the protocol).
  • Females of child-bearing potential must be willing to use an effective method of contraception, for the course of the study through at least 6 months after the last dose of study medication.
  • Males who have Women of Child-bearing Potential (WOCBP) partners must agree to use effective method of contraception for the course of the study through 8 months after the last dose of study medication.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Who cannot join

  • Patients currently receiving any other investigational agents, immunomodulatory agents, chemotherapy, or TKIs. EGFR mutation-positive patients must have received prior TKI treatment
  • Any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy.
  • Untreated CNS metastases that are >1 cm in size are excluded, even if they are asymptomatic. Patients with treated brain metastases will be allowed if brain imaging obtained within 30 days of trial enrollment reveals stable disease.
  • Cirrhosis at a level of Child-Pugh B or worse, or cirrhosis of any degree and a history of hepatic encephalopathy, or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
  • Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
  • Uncontrolled or poorly-controlled hypertension (>150 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management
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  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
  • Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
  • History of abdominal or tracheosphageal fistula or gastrointestinal perforation within 6 months prior to randomization
  • Clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
  • Serious, non-healing wound, active ulcer, or untreated bone fracture within 28 days prior to first dose of protocol therapy
  • Subjects with a history of smoking greater than a 100 cigarettes in a lifetime, unless their tumor has an EGFR exon 19 or exon 21 mutation.
  • Patients with active, suspected, or known autoimmune disease that has required systemic treatment in the past one year (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Hormone replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Patients with a history of hemoptysis (defined as bright red blood or ≥1/2 teaspoons) within 1 month prior to first dose of protocol therapy or with radiographic evidence of major blood vessel invasion or encasement by cancer.
  • Undergone major surgery within 28 days prior to first dose of study treatment, or minor surgery/ subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.
  • Receiving chronic anti-platelet therapy other than aspirin, including non-steroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted. Occasional use of NSAIDs is allowed (for example daily use for less than a week; treating physician discretion is permitted to differentiate between occasional vs chronic use)
  • Have not recovered from adverse events due to agents administered earlier except neuropathy and alopecia. Physician's discretion is allowed to decide which unresolved adverse events from previous therapy (for NSCLC) prohibit patient participation in this study.
  • Requiring more than 10 mg prednisolone (or its equivalent) per day are excluded.
  • Any evidence of interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or pneumonitis requiring oral or IV glucocorticoids. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Patients with known latent or active tuberculosis infection are excluded.
  • Have received a live vaccine within 30 days prior to cycle 1 Day 1.
  • Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (significant), cirrhosis, or psychiatric illness/ social situations that would limit compliance with the study requirements.
  • Known history of testing positive for immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Known history of chronic hepatitis B virus infection or chronic hepatitis C virus indicating chronic infection that is not cured.
  • Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers, such as, bladder, gastric, colon, cervical/ dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study registration and no additional therapy is required or anticipated to be required during the study period.
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Requiring pain medication must be on a stable regimen at study entry.
  • Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
  • Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization.
  • Ca > 12 mg/dl or corrected serum calcium > ULN
  • Patients who are receiving denosumab prior to randomization must be willing and eligible to receive a bisphosphonate instead while in the study
  • Pregnant or breast feeding
  • Known hypersensitivity to Chinese hamster ovary cell products or any of the study drugs.
  • Prior allogeneic bone marrow transplantation or solid organ transplant
  • Clear tumor infiltration into the thoracic great vessels is seen on imaging
  • Clear cavitation of pulmonary lesions is seen on imaging
  • Diagnosis of squamous cell carcinoma of the lung.
  • Lung tumor with a known ALK or ROS1 rearrangement or an EGFR mutation other than in exon 19 or exon 21.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: TH-138: Phase II Randomized Trial of Carboplatin + Pemetrexed + Bevacizumab, With or Without Atezolizumab in Stage IV Non-squamous NSCLC Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked

While cigarette smoking remains the primary cause of most lung cancer cases, lung carcinoma in never smokers account for nearly 20 percent of cases. Never smokers with lung cancer typically present with different molecular profiles from that of smokers, which results in prognostic and therapeutic implications. Molecular changes in NSCLC that have therapeutic significance include mutations in the epidermal growth factor receptor (EGFR) and rearrangements in the anaplastic lymphoma kinase (ALK) gene. These driver mutations typically are present in lung tumors found in never or light smokers.

The addition of bevacizumab to carboplatin and paclitaxel in first-line treatment of non-squamous NSCLC showed improved survival compared to carboplatin and paclitaxel alone, 12.3 vs. 10.3 months respectively. Results from the POINTBREAK trial demonstrated that carboplatin + pemetrexed + bevacizumab is an alternative option to carboplatin + paclitaxel + bevacizumab, with comparable survival but less toxicity. In recent years, immunotherapy has emerged as a form of treatment that can lead to robust responses in a subset of patients. The PD-1 inhibitor nivolumab and the PD-L1 inhibitor atezolizumab have shown prolonged survival in comparison to docetaxel in patients who previously progressed with chemotherapy, irrespective of PD-L1 expression. Thus, this study combines immunotherapeutic agent atezolozumab with an ant-angiogenic agent, bevacizumab, and double platinum therapy (carboplatin and pemetrexed).

Being tested
Arm A, Arm B
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Arm ADrug

    Carboplatin + Pemetrexed + Bevacizumab + Atezolizumab

  • Arm BDrug

    Carboplatin + Pemetrexed + Bevacizumab

Study groups in NCT03786692
Study groupRoleWhat they receive
Arm AExperimentalArm A: Carboplatin + Pemetrexed + Bevacizumab + Atezolizumab Maintenance: Pemetrexed + Bevacizumab + Atezolizumab
Receives: Drug: Arm A
Arm BActive comparatorArm B: Carboplatin + Pemetrexed + Bevacizumab Maintenance: Pemetrexed + Bevacizumab
Receives: Drug: Arm B

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    Time a patient shows progression of disease from the time of intervention

    Measured: 12.5 months

Secondary outcomes (3)

  1. To perform a safety analysis in all treated subjects: NCI CTCAE v 5.0

    Observe safety of combination as per NCI CTCAE v 5.0

    Measured: 15 months

  2. To compare the overall response rate (ORR) of Arm A to Arm B

    ORR is defined as the portion of patients with partial or complete response as measured using RECIST 1.1 criteria

    Measured: 15 months

  3. To compare the duration of response of Arm A to Arm B

    Time from documentation of tumor response to disease progression, measured using RECIST 1.1 criteria

    Measured: 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Dec 2018
  2. Study start4 Sep 2019
  3. Primary completionDec 2026 (estimated)
  4. Study completionJan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The design of this study will be an open label, randomized, phase 2 study in adult (≥ 18 years) male and female subjects with stage IV disease who have never smoked, irrespective of their driver mutation status, as well as subjects who have tumors that possess a driver mutation. The study will be comparing the four agent treatment group (Arm A) that includes carboplatin + pemetrexed + bevacizumab + atezolizumab versus a three agent control group (Arm B) that includes carboplatin + pemetrexed + bevacizumab for 4 cycles, each cycle lasting for 3 weeks. Treatment will be followed by maintenance in both arms that will include all agents except carboplatin. There is no crossover in this study. 1. Arm A: Carboplatin + Pemetrexed + Bevacizumab + Atezolizumab Maintenance: Pemetrexed + Bevacizumab + Atezolizumab 2. Arm B: Carboplatin + Pemetrexed + Bevacizumab Maintenance: Pemetrexed + Bevacizumab
Masking
None (open label)
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03786692
Sponsor's protocol ID
TH-138
Other IDs
18-1077
Status last verified
May 2026
First submitted
21 Dec 2018
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bodor JN, Patel JD, Wakelee HA, Levy BP, Borghaei H, Pellini B, Costello MR, Dowell JE, Finley G, Huang CH, Neal JW, Nieva JJ, Puri S, Socinski MA, Thomas C, Ross EA, Litwin S, Clapper ML, Treat J. Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked. Clin Lung Cancer. 2023 Nov;24(7):e242-e246. doi: 10.1016/j.cllc.2023.05.003. Epub 2023 May 11.

    PubMed 37451930

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Arm A and Arm B in people with Non-Small Cell Carcinoma of Lung, TNM Stage 4, run by Fox Chase Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: 12.5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03786692, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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