Phase II Randomized Trial of Carboplatin+Pemetrexed+Bevacizumab+/- Atezolizumab in Stage IV NSCLC
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|ClinicalTrials.gov Identifier: NCT03786692|
Recruitment Status : Not yet recruiting
First Posted : December 25, 2018
Last Update Posted : April 8, 2019
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).
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Carcinoma of Lung, TNM Stage 4||Drug: Arm A Drug: Arm B||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||117 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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.
|Masking:||None (Open Label)|
|Official Title:||TH-138: Phase II Randomized Trial of Carboplatin + Pemetrexed + Bevacizumab, With or Without Atezolizumab in Stage IV NSCLC Patients Who Have Never Smoked or Have a Driver Mutation|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||January 2024|
Experimental: Arm A
Arm A: Carboplatin + Pemetrexed + Bevacizumab + Atezolizumab Maintenance: Pemetrexed + Bevacizumab + Atezolizumab
Drug: Arm A
Carboplatin + Pemetrexed + Bevacizumab + Atezolizumab
Active Comparator: Arm B
Arm B: Carboplatin + Pemetrexed + Bevacizumab Maintenance: Pemetrexed + Bevacizumab
Drug: Arm B
Carboplatin + Pemetrexed + Bevacizumab
- Progression free survival [ Time Frame: 12.5 months ]Time a patient shows progression of disease from the time of intervention
- To perform a safety analysis in all treated subjects: NCI CTCAE v 5.0 [ Time Frame: 15 months ]Observe safety of combination as per NCI CTCAE v 5.0
- To compare the overall response rate (ORR) of Arm A to Arm B [ Time Frame: 15 months ]ORR is defined as the portion of patients with partial or complete response as measured using RECIST 1.1 criteria
- To compare the duration of response of Arm A to Arm B [ Time Frame: 15 months ]Time from documentation of tumor response to disease progression, measured using RECIST 1.1 criteria
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786692
|Contact: Joseph Treat, MD||215-214-4297||Joseph.Treat2@fccc.edu|
|Principal Investigator:||Joseph Treat, MD||Fox Chase Cancer Center|