GSK1120212+GSK2141795 for Cervical Cancer
|ClinicalTrials.gov Identifier: NCT01958112|
Recruitment Status : Terminated (Drug supply)
First Posted : October 8, 2013
Last Update Posted : August 21, 2017
This research study is evaluating the combination of two drugs called GSK1120212 (trametinib) and GSK2141795 as a possible treatment for recurrent or persistent cervical cancer. Trametinib and GSK2141795 are drugs that may stop cancer cells from growing. Trametinib is a MEK inhibitor - it blocks a protein called MEK that is commonly overactive in tumor cells. GSK2141795 is an AKT inhibitor which blocks a pathway in cancer cells that is commonly overactive in tumor cells called the PI3kinase pathway. In this research study, the investigator is looking to see whether the combination of Trametinib and GSK2141795 is useful in treating recurrent and persistent cervical cancer.
Additionally, the investigator is looking to see if participants whose tumors contain a particular genetic make-up will have better response to combination trametinib and GSK2141795. Participants' tumors will be tested for mutations in genes which could make some cancers more susceptible to trametinib and GSK2141795.
|Condition or disease||Intervention/treatment||Phase|
|Cervical Cancer||Drug: GSK1120212 (trametinib) Drug: GSK2141795||Phase 2|
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Before the research starts (screening): The participant will be asked to undergo some screening tests or procedures to find out if they can be in the research study. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the participant does not take part in the research study. If the participant has had some of these tests or procedures recently, they may or may not have to be repeated.
- A medical history, which includes questions about the participant's health, current medications, and any allergies.
- Physical exam, including height and weight
- An eye exam, by an eye specialist
- Performance status, the investigator will ask the participant questions about how they are able to carry on with your usual activities.
- Vital signs, including blood pressure, pulse, body temperature and respiratory rate
- An assessment of the participant's tumor by CT (Computerized Tomography) scan or MRI (Magnetic Resonance Imaging), of their chest, stomach area, and pelvis.
- Blood tests (approximately 2-3 tablespoons) including hematology, chemistry, liver function, kidney function, blood sugar levels, blood clotting levels
- Electrocardiogram (EKG), a test to check the participant's heart's rhythm
- Echocardiogram (ECHO), a test to check the participant's heart's structure and function.
- Serum pregnancy test if the participant are capable of becoming pregnant
If the results of the above tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.
If these tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.
Additional research procedures to be performed at the time of screening:
- Archival tumor testing: During this study, additional tests will be performed on a sample of the participant's original tumor that has been stored in your institution's tissue banks. These tests will be performed on tumor tissue samples from previous biopsies or surgeries for the participant's cancer. The research done on these samples will involve looking at DNA and proteins in the participant's cancer to see if researchers can learn more about the participant's type of cancer and understand how trametinib and GSK2141795 might work on their tumor. Testing of this sample will not require the participant to undergo any additional procedures.
TISSUE COLLECTIONS/OWNERSHIP: Participation in this protocol involves providing specimen(s) of the participant's tissue. Please know that if the investigator leaves the institution, the research and the tissue might remain at the DF/HCC or might be transferred to another institution.
- Additional Blood tests: Approximately 2 tablespoons of blood will be collected for research testing. This testing will involve looking at DNA and proteins in the participant's blood to compare them with those seen in their cancer. This will be drawn before the participant begin taking the study drug. These research sample collections are a required part of this research study. If the participant does not wish to undergo these procedures, the participant may not participate in this research study.
- Optional pre and post tumor biopsies: Before the participant begin receiving the study drug, your doctor will arrange for a procedure where your tumor will be biopsied. Your entire tumor or part of your tumor might be removed (excisional biopsy) or a small sample of the tumor might be removed using a needle (needle biopsy, fine needle aspirate) with guidance under radiographic studies. This will also occur before the participant begins treatment and between 2-4 weeks after treatment has started.
After the screening procedures confirm that the participant is eligible to participate in the research study:
If the participant decides to take part in this research study, the participant will be given a study drug diary for each treatment cycle. The participant will be asked to complete a drug diary to record when they took each dose or to give a reason if the participant did not take the study drugs. At the end of each cycle, the participant should return the pill bottles and all of the remaining pills prior to starting the next cycle. The participant will receive a new set of pills and new diary if the participant is to continue the next cycle.
Clinical Exams: During all cycles the participant will have a physical exam, and will be asked questions about their general health and specific questions about any problems that they might having and any medications the participant may be taking.
The participant can expect the following while they are a participant on this study.
At the beginning of each cycle (one cycle equals 28 days):
- Recording of any health problems, including side effects of the study drugs
- List of medications taken since the last visit
- Physical examination (including measurement of vital signs, such as blood pressure, breathing rate, heart rate, temperature and weight)
- Evaluation of the participant's performance status (the ability to carry on daily activities)
- Blood samples (approximately 2-3 tablespoons of blood will be taken) to evaluate the participant's blood counts, electrolytes, liver function, kidney function and blood sugar levels.
- EKG, a test to check the participant's heart's rhythm. This will be performed at the start on each cycle.
Once a week during the first cycle:
- The participant will be called by a member of the study team to record any health problems, including side effects from the study drugs and any changes in medications.
- Blood samples (approximately 1 teaspoon of blood will be taken) to evaluate their blood sugar levels. This can be done at a lab close to home. If the participant's doctor thinks that their blood sugars need further monitoring, the participant may have continued blood samples drawn to check their blood sugar weekly or daily past the first cycle.
Every 2 cycles:
- Blood samples (approximately 1 teaspoon of blood will be taken) to evaluate the participant's HgbA1C, a test that evaluates their blood sugar levels over a period of time. This can be done at a lab close to home.
- CT scan or MRI of your chest, stomach area, and pelvis to see if the participant's cancer is increasing, decreasing, or staying the same size. If the cancer is decreasing, the participant's doctor may schedule the participant for another CT scan in about one month to check it again.
- ECHO, a test to check the participant's heart's structure and function
At the end of the study:
- Recording of any health problems, including any side effects from the study drugs.
- List of medications taken since the last visit
- Physical examination (including measurement of the participant's vital signs, such as blood pressure, breathing rate, heart rate, temperature, and weight.)
- Evaluation of the participant's performance status (their ability to carry on daily activities).
- Blood samples (approximately 2-3 tablespoons of blood will be taken) to evaluate the participant's blood counts, electrolytes, liver function, kidney function, blood sugar level, and HgbA1C.
After the final dose of the study drug:
The investigator would like to keep track of the participant's medical condition for up to 3 years after the participant completes the study. The investigator would like to do this by calling the participant on the telephone or seeing the participant in clinic for evaluation of their status, disease and current therapy. Keeping in touch with the participant and checking their condition routinely helps us look at the long-term effects of the research study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single Arm, Single Stage Phase II Trial of GSK1120212 and GSK2141795 in Persistent or Recurrent Cervical Cancer|
|Study Start Date :||October 2013|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||March 2020|
Experimental: GSK1120212 (trametinib) and GSK2141795
GSK1120212 (trametinib) 1.5 mg QD + GSK2141795 50 mg QD in 28 day cycles
Drug: GSK1120212 (trametinib)
Trametinib dose is 1.5 mg orally once per day
Other Name: Trametinib
The dose of GSK2141795 is 50 mg orally once per day
- Response Rate for the combination of GSK1120212 (trametinib) and GSK2141795 in patients with recurrent or persistent cervical cancer. [ Time Frame: 2 Years ]Response rate will be assessed by RECIST version 1.1.
- Duration of progression-free (PFS) [ Time Frame: 2 Years ]The duration of progression-free (PFS) following initiation of therapy with GSK1120212 (trametinib) and GSK2141795 will be measured.
- Toxicity of GSK1120212 (trametinib) and GSK2141795. [ Time Frame: 2 Years ]Toxicity will be assessed for this combination by version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) in this cohort of patients.
- Mutation and co-mutation rates of genes in the PI3K and RAS ERK signaling pathways in recurrent cervical cancer using high throughput targeted mutational analysis on participant tumor samples. [ Time Frame: 2 Years ]The mutation and co-mutation rates of genes in the PI3K and RAS ERK signaling pathways in recurrent cervical cancer will be interrogated using high throughput targeted mutational analysis on participant tumor samples.
- Association of mutational status with clinical benefit from GSK1120212 (trametinib) and GSK2141795. [ Time Frame: 2 Years ]The association of mutational status along with clinical benefit from GSK1120212 (trametinib) and GSK2141795 will be explored in this study.
- Overall survival [ Time Frame: 2 years ]Overall survival will be determined for subjects on this study
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01958112
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Ursula A. Matulonis, MD||Dana-Farber Cancer Institute|