MK-1775 for Advanced Solid Tumors
- MK-1775 is a cancer treatment drug that acts against tumor cells. It appears to block a protein that affects other proteins inside the cell that can help the tumors grow. However, it has not been fully tested in humans. Researchers want to see if it is safe and effective against advanced solid tumors that have not responded to treatment.
- To see if MK-1775 is a safe and effective treatment for advanced solid tumors.
- Individuals at least 18 years of age who have advanced solid tumors that have not responded to treatment.
- Participants will be screened with a physical exam and medical history. Blood, urine, and tumor samples will be collected. Imaging studies will also be performed.
- Participants will take MK-1775 by mouth for 21-day cycles of treatment. They will have two doses on day 1, two doses on day 2, and one on day 3, with no treatment for the remaining days. Participants will keep a study diary to record their doses and any side effects.
- Some participants will have 2 weeks of MK-1775 for each cycle. They will repeat the dose schedule for days 1 through 3 on days 8 through 10.
- Treatment will be monitored with frequent blood tests and imaging studies. Additional blood and tumor samples may be collected.
- Treatment with MK-1775 will continue as long as the tumor does not grow and side effects are not severe.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Single-agent MK-1775, a Wee1 Inhibitor, in Patients With Advanced Refractory Solid Tumors|
- To determine the pharmacokinetics of MK-1775 in patients with refractory solid tumors [ Time Frame: January, 2014 ]
- To establish the safety and tolerability of single-agent MK-1775 in patients with refractory solid tumors. [ Time Frame: January, 2014 ]
- Determine the effect of MK-1775 on MAKERS DNA damage and apoptosis [ Time Frame: January, 2014 ]
- Evaluate the antitumor activity of MK-1775 in patients with refractory solid tumors [ Time Frame: January, 2014 ]
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
- Wee1 is a tyrosine kinase involved in the phosphorylation and inactivation of cyclindependent kinase 1 (CDK1/CDC2)-bound cyclin B, resulting in G2 cell cycle arrest in response to DNA damage to allow time for DNA repair. Recent preclinical data additionally implicates Wee1 in maintenance of genomic integrity during S phase.
- MK-1775 is a selective inhibitor of Wee1 kinase. Recent preclinical model data additionally show single agent anti-tumor activity in multiple cancer cell lines and tumor xenografts.
- Preliminary data show MK-1775 is tolerable at lower doses in combination with chemotherapeutic agents. We propose to demonstrate single-agent activity for MK-1775.
- To establish the safety and tolerability of single-agent MK-1775 in patients with refractory solid tumors
- To determine the pharmacokinetics of MK-1775 in patients with refractory solid tumors
- To determine the effect of MK-1775 on markers of DNA damage and apoptosis in tumor tissue and circulating tumor cells
- To evaluate the antitumor activity of MK-1775 in patients with refractory solid tumors
- Patients must have histologically confirmed solid tumors for which all standard therapy known to prolong survival have failed, or for which standard therapies do not exist.
- No major surgery, radiation, or chemotherapy within 4 weeks prior to entering the study
- Adequate organ function
- This study will follow a traditional 3+3 design.
- For dose level 1, MK-1775 will be administered orally for 5 doses each cycle. Starting at dose level 2 and onwards, MK-1775 will be administered orally for 5 doses for the first 2 weeks of each cycle . Each cycle is 21 days ( 1 day for scheduling).
- Once MTD is established, 6 additional patients will be enrolled at the MTD to further evaluate that dose for PK and PD endpoints.
- A further expansion cohort of 6 additional patients with documented tumors harboring BRCA-1 or -2 mutations will lso be enrolled at the MTD to further explore the safety of the agent and obtain preliminary evidence of activity in this patient population.
- During the escalation phase, tumor biopsies will be optional and will be evaluated for pharmacodynamic (PD) studies for evidence of DNA damage, repair, and apoptosis (H2AX, pNbs1, ERCC1, and caspase 3). During the expansion phase, once MTD is reached, mandatory paired tumor biopsies will be pursued in the 6 additional patients enrolled at the MTD to further evaluate PD endpoints.
|Contact: Jennifer H Zlott||(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)|