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MLN9708 and Vorinostat in Patients With Advanced p53 Mutant Malignancies

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Cancers

Intervention: MLN9708 (Drug); Vorinostat (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Siqing Fu, MD,PHD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Siqing Fu, MD,PHD, Phone: 713-563-1930

Summary

The goal of this clinical research study is to find the highest tolerable dose of the combination of MLN9708 and vorinostat that can be given to patients with advanced solid tumors. The safety of these drugs will also be studied.

Clinical Details

Official title: A Phase I Study of MLN9708 and Vorinostat to Target Autophagy in Patients With Advanced p53 Mutant Malignancies

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Doses (MTD) of MLN9708 and Vorinostat

Secondary outcome: Tumor Response

Detailed description: Study Groups: If you are found to be eligible to take part in this study, you will be assigned to a dose level of MLN9708 and vorinostat based on when you join this study. Up to 4 dose levels of the MLN9708 and vorinostat combination will be tested. Up to 6 participants will be enrolled at each dose level combination. The first group of participants will receive the lowest dose level combination. Each new group will receive a higher dose of either MLN9708 or vorinostat than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose combination of MLN9708 and vorinostat is found or all 4 dose levels are filled. Up to an additional 14 participants will be enrolled in the highest dose level of the study drug combination. The dose of the study drug combination that you receive may be lowered if you have intolerable side effects. Study Drug Administration: Each study cycle is 28 days. You will take MLN9708 capsules by mouth every 7 days (on Days 1, 8, and 15 of every cycle). You should swallow MLN9708 capsules whole with 8 ounces (1 cup) of water. Each capsule should be swallowed separately with a sip of water. Do not break, chew, or open the capsules. Each dose should be taken on an empty stomach, at least 1 hour before or 2 hours after a meal. If you miss a dose, take it as soon as you remember, as long as the next scheduled dose is at least 72 hours (3 days) away. You should not take a double dose to make up for a missed dose. If you vomit after taking a dose, wait until the next scheduled dose. Do not take an additional dose. You will take vorinostat capsules by mouth on Days 1-21 of each cycle, followed by a break of 7 days. You should swallow vorinostat capsules whole with water. Do not break, chew, or open the capsules. Vorinostat should be taken with food. If you miss a dose, take it as soon as you remember, as long as the next scheduled dose is at least 12 hours away. You should not take a double dose to make up for a missed dose. If you vomit after taking a dose, wait until the next scheduled dose. Do not take an additional dose. It is important that you tell your doctor if you have any side effects while on this study. If you have side effects or abnormal test results, you may be asked to return to the clinic for more tests until the side effects or abnormal test results improve. Your dose of study drug may be changed and/or you may be given drugs to help control the side effects. Study Visits: One (1) time each week during Cycle 1: ° Blood (about 6 teaspoons) will be drawn for routine tests and to check your liver and kidney function. On Day 1 of Cycles 2 and beyond:

- You will have a physical exam.

- Blood (about 6 teaspoons) will be drawn for routine tests.

- If your doctor thinks it is needed, urine will be collected for routine tests.

At the end of Cycles 2 and beyond:

- You will have a CT, PET, and/or MRI scan to check the status of the disease. If your

doctor thinks it is needed, you may have measurement sooner.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to

measure tumor markers. Tumor markers can be used to check the status of the disease. Any time the doctor thinks it is needed:

- Blood (about 6 teaspoons) will be drawn for routine tests.

- If you can become pregnant, blood (about 1 teaspoon) will be collected for a pregnancy

test.

- You will have an EKG to check your heart function.

Length of Study: You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, if you develop new health problems, or if you are no longer able to follow study directions. You may choose to stop taking the study drugs at any time. You should tell the study doctor right away if you are thinking about no longer taking part in this study. The study doctor will talk to you about how to safely stop taking the study drugs. Your participation on the study will be over after the end-of-study visit. End of Study Visit: Within 30 days after your last dose of the study drugs, the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 7 teaspoons) will be drawn for routine tests, tests of your kidney and

liver function, and tumor marker testing.

- You will have a CT, PET, and/or MRI scan to check the status of the disease. If your

doctor thinks it is needed, you may have a scan performed sooner. This is an investigational study. MLN9708 is not FDA approved or commercially available. MLN9708 is currently being used for research purposes only. Vorinostat is FDA approved and commercially available to treat advanced cutaneous T-cell lymphoma. The study doctor can explain how the study drugs are designed to work. Up to 56 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Male or female patients 18 years or older. 2. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 3. Female patients who: • Are postmenopausal for at least 1 year before the screening visit, OR • Are surgically sterile, OR • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) 4. Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following: • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) 5. Patients must have a diagnosis with solid tumors and lymphomas, either refractory to standard therapy or for which no effective standard therapy that conveys clinical benefit. 6. Patients must have a p53 mutation which is defined as cytoplasmic positivity by immunohistochemistry and/or next gene mutation sequencing. 7. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2. 8. Patients must meet the following clinical laboratory criteria: Absolute neutrophil count (ANC) >/= 1,000/mm^3 and platelet count >/= 75,000/mm^3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Total bilirubin /= 30 mL/min. 9. Patients may receive local palliative radiation therapy immediately before or during the treatment if the radiation therapy is not delivered to the sole target lesions. 10. Measurable or evaluable disease will be included as assessed by RECIST 1. 1. Exclusion Criteria: 1. Female patients who are lactating or have a positive blood pregnancy test during the screening period. 2. Failure to have fully recovered (ie, /= Grade 2 peripheral neuropathy 15. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21days of the start of this trial and throughout the duration of this trial.

Locations and Contacts

Siqing Fu, MD,PHD, Phone: 713-563-1930

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: June 2014
Last updated: August 20, 2015

Page last updated: August 23, 2015

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