NCI-MPACT: Molecular Profiling-Based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors
- Variations in the genes in some tumors play an important role in how a cancer grows and develops. Looking at these variations and finding drugs that target them is one possible way to treat cancer. However, researchers do not yet know if this way works better than standard cancer treatments. Researchers are interested in studying people who have tumor gene variations in different types of cancer cells. They want to see if these people benefit more from being treated with a drug that specifically targets that variation than from being treated with drugs that do not. To do so, they will look at the genes from people with different sorts of cancers. Based on this analysis, they will offer treatments based on the specific gene variations found on the tumor cells.
- To see if choosing specific treatment options for tumor gene variations is more safe and effective than standard cancer treatments.
- Individuals at least 18 years of age who have advanced solid tumors that have not responded to standard treatments.
- This study will try four different drugs or drug combinations for cancer treatment. Some of these treatments target specific tumor gene variations, while others do not. However, all drugs are intended to be used as possible cancer treatment options.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and heart and lung function tests will also be performed.
- Participants will provide a tumor tissue sample for study. This sample will be used to determine possible tumor gene variations.
- Participants will be divided into groups based on their tumor gene variation. Within these groups, they will be further divided into two possible study arms. One arm will receive a drug or drug combination designed to target the tumor gene variation. The other arm will receive a drug or drug combination that is not designed to target the variation.
- Participants will receive their study drugs according to the standard dosing schedule for their treatment. Treatment will be monitored with frequent blood tests and imaging studies. If the cancer gets worse while a participant is on a study drug not designed to work on the tumor s gene variation, the study doctors may change the drug to one thought to work on that variation.
- Participants will have frequent follow-up visits to monitor the outcome of the treatment. These visits may include additional tumor biopsies.
Drug: Trametinib DMSO
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
|Official Title:||Molecular Profiling-based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors|
- Compare response rate and/or 4-month PFS for agents chosen based on presence of specific tumor mutations/amplifications with response rate for agents randomly chosen from complementary set of agents not identified to target mutations of interest... [ Time Frame: 1.5 - 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Receive an agent from the set corresponding to one of their mutation/amplication categories.
N/ADrug: Trametinib DMSO
Active Comparator: Arm B
Receive an agent chosen, by physician choice, from the complementary set (not corresponding to one of their mutation/amplication categories).
N/ADrug: Trametinib DMSO
-Targeted therapy based on identifying underlying genetic aberrations within the tumor is the goal of personalized medicine. This pilot trial aims to establish whether advanced cancer patients who have no treatment options with proven benefit, and with tumor mutations/amplifications in one of 3 genetic pathways (DNA repair, PI3K, or RAS/RAF) are more likely to derive clinical benefit if treated with agents targeting that pathway than if treated with agents that do not. Each patient will be randomly assigned to receive the recommended Phase II dose of either a study drug identified to work on their tumor s mutation/aberrant pathway, or an agent from the complementary set not identified to work on the mutations/amplifications of interest.
-Compare the response rate (CR+PR) and/or 4-month PFS for treatment with agents chosen based on the presence of specific mutations/amplifications in patient tumors with the response rate for treatment with agents randomly chosen from the complementary set of agents not identified to work on the mutations/amplifications of interest.
- Adult patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy and/or for which no standard treatment is available that has been shown to improve survival.
- Tumor amenable to percutaneous biopsy, and willingness to undergo tumor biopsy.
Patients enrolled on study will have a tumor biopsy sequenced in a CLIA-certified lab for specific mutations/amplifications of interest: DNA repair pathways, PI3K pathway, or RAS/RAF/MEK pathway. If such mutations are not detected, the patient will be taken off study.
- Patients with melanoma and known BRAF V600E mutations need to have received and progressed on specific BRAF inhibitor therapy.
- Patients with ovarian or breast cancer and BRCA mutations will not receive ABT-888 on study for the treatment of BRCA-positive tumors. They will only be eligible to receive any of the study treatments if they have other mutations of interest.
- Patients with NSCLC should have been previously tested for the presence of EGFR and ALK mutations, and, if detected, should have received and progressed on EGFR or ALK TKI therapy.
- Patients in whom a mutation of interest is detected will be randomized 2:1 into Arms A or B: Arm A will receive an agent prospectively identified to target that mutation/pathway; Arm B will receive an agent from the complementary set (not prospectively identified to target one of their mutations). Patients in Arm B will be allowed to cross over at the time of disease progression to a treatment regimen based on their mutational analysis.
- Targeted drugs will be administered at recommended Phase II doses and schedules: (1) ABT-888 (PARP inhibitor) with temozolomide for defects in the DNA repair pathway; (2) MK-1775 (Wee1 inhibitor) plus carboplatin for defects in DNA repair pathway; (3) Everolimus (mTOR inhibitor) for mutations in the PI3K pathway; or (4) Trametinib DMSO (MEK inhibitor) for mutations in the RAS/RAF/MEK pathway.
- Given the relative frequencies of the mutations, approximately 700 patients will need to be enrolled to acquire 180 evaluable patients; the initial feasibility part of the trial will be conducted in the first 60 evaluable patients, requiring enrollment of 100-150 patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01827384
|Contact: Ramya Antony||(301) firstname.lastname@example.org|
|Contact: Shivaani Kummar, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|