A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC
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|ClinicalTrials.gov Identifier: NCT03202940|
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : June 12, 2018
This research study is studying a drug combination as a possible treatment for anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer.
The drugs involved in this study are:
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer||Drug: Alectinib Drug: Cobimetinib||Phase 1 Phase 2|
This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of investigational drugs or new combinations of approved drugs. In addition, a Phase I study tries to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied. Following the phase I study, additional participants will be enrolled to the Phase II component. The phase II component will test the safest doses of alectinib and cobimetinib (as identified in the Phase I component) in a larger group of patients.
The FDA (the U.S. Food and Drug Administration) has approved alectinib as a treatment option for this disease.
The FDA has not approved cobimetinib as a treatment for this specific disease. However, cobimetinib is approved for treatment of melanoma, another type of cancer.
Alectinib is an oral ALK inhibitor made by the pharmaceutical company Genentech. The term ALK inhibitor means that alectinib targets the abnormal ALK protein that is causing your lung cancer cells to grow. Alectinib has been tested in other clinical research studies and results show that the drug may help stop the growth and spread of ALK+ lung cancer cells.
Cobimetinib is an oral inhibitor of MEK, a signaling protein that can cause some types of lung cancer to grow. Cobimetinib is also made by Genentech. Laboratory studies suggest that ALK and MEK may work together to help ALK+ lung cancer cells grow. In the laboratory, combination treatment with drugs targeting ALK and MEK prevented lung cancer cells from growing. It is possible that combination treatment with alectinib and cobimetinib will work better than alectinib alone to control the spread of the cancer.
In this research study, the investigators are trying to determine whether the combination of alectinib and cobimetinib is safe and well tolerated. This study will help determine the doses of the drugs that should be used in the Phase II portion of this study. Another purpose of this study is to determine whether adding cobimetinib to alectinib is effective for treating lung cancer that has already stopped responding to alectinib alone. In order to help understand why the cancer may have stopped responding to alectinib and whether treatment with the two drugs effectively blocks growth signals, all participants in this study will have periodic blood collections and undergo multiple biopsies.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC|
|Actual Study Start Date :||September 14, 2017|
|Estimated Primary Completion Date :||August 30, 2019|
|Estimated Study Completion Date :||August 30, 2020|
Experimental: Cobimetinib + Alectinib
Alectinib administered twice daily at pre-determined dosage orally Cobimetinib administered daily at pre-determined dosage orally
Alectinib is an oral ALK inhibitor. The term ALK inhibitor means that alectinib targets the abnormal ALK protein that is causing lung cancer cells to grow
Other Name: Alecensa
Cobimetinib is an oral inhibitor of MEK, a signaling protein that can cause some types of lung cancer to grow
Other Name: Cotellic
- Maximum tolerated dose as assessed by CTCAE v4.0 [ Time Frame: 28 days ]The highest dose of the combination of alectinib and cobimetinib that does not cause unacceptable side effects. The maximum tolerated dose is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.
- The objective response rate, including partial and complete responses, as evaluated by RECIST v1.1 [ Time Frame: 2 years ]Objective response rate (partial and complete responses) will be evaluated according to RECIST v1.1 criteria
- Progression Free Survival as assessed by RECIST v1.1 and the Kaplan-Meier method [ Time Frame: 2 years ]PFS will be defined as the time from the start of study drug treatment to the date of the first documented progression or death due to disease. The distribution of PFS will be estimated using the Kaplan-Meier method.
- Overall Survival as assessed by the Kaplan-Meier method [ Time Frame: 2 years ]Overall survival (OS) is defined as the time from the date of the first dose of the study drug to the date of death due to any cause. OS time for patients who are alive at the end of the study or are lost to follow-up will be censored at the date of the last contact. OS will be estimated using the Kaplan-Meier method.
- Safety/Tolerability, or the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]Number of patients with treatment-related adverse events, according to CTCAE v4.0
- Duration of Response as assessed by RECIST v1.1. [ Time Frame: 2 years ]The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. This calculation will take as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported will be censored at the last disease evaluation.
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): NCT03202940
|Contact: Alice T Shaw, MD, PhD||617-643-0563||Ashaw1@partners.org|
|United States, Massachusetts|
|Massachusetts general Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Alice T Shaw, MD, PhD 617-643-0563 Ashaw1@partners.org|
|Principal Investigator: Alice T Shaw, MD, PhD|
|Principal Investigator:||Alice T Shaw, MD, PhD||Massachusetts General Hospital|