MK-4827 in Combination With Pegylated Liposomal Doxorubicin in Participants With Advanced Solid Tumors and Ovarian Cancer (MK-4827-011)

October 18, 2016 updated by: Tesaro, Inc.

A Phase Ib Dose Escalation Study of MK-4827 in Combination With Pegylated Liposomal Doxorubicin (Doxil™ or Caelyx™) in Patients With Advanced Solid Tumors With a Cohort Expansion in Patients With Platinum Resistant/Refractory High Grade Serous Ovarian Cancer

This study will determine whether MK-4827 can be safely administered in combination with pegylated liposomal doxorubicin, and if so, will obtain an estimate of the benefit of the combination in patients with ovarian cancer as compared to historical data with single agent pegylated liposomal doxorubicin. The first part of the study (Part A) is designed to determine the maximum tolerated dose (MTD) and evaluate the safety of MK-4827, when administered in combination with pegylated liposomal doxorubicin. Part B is designed to assess preliminary clinical activity of MK-4827, when administered in combination with pegylated liposomal doxorubicin to participants with ovarian cancer. It is hypothesized that MK-4827 can be administered, in conjunction with pegylated liposomal doxorubicin, with acceptable tolerability and that MK-4827, administered in conjunction with pegylated liposomal doxorubicin, will demonstrate a tumor response rate equal or superior to that of historical data for pegylated liposomal doxorubicin alone.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The decision to discontinue new enrollment is not related to any concerns about the safety profile of the product.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Parts A and B:

  • The participant has a locally advanced or metastatic solid tumor and lacks curative options

    • Pegylated liposomal doxorubicin must be an appropriate therapy or the participant has not responded to standard of care or therapies known to provide clinical benefit, or has refused such therapies or no therapy is known to provide clinical benefit

  • Part B only: Female participants must have high grade serous ovarian cancer without curative options; pegylated liposomal doxorubicin must be an appropriate therapy. Eligible patients for Part B must have:

    • Platinum-resistant ovarian cancer, defined as tumor progression within 6 months of completing treatment with a platinum-containing agent, OR secondary platinum-refractory ovarian cancer defined as tumor progression while on treatment for recurrent ovarian cancer after initially responding to a platinum-based chemotherapy regimen in the first line setting; and
    • Measurable disease, OR elevated serum cancer antigen 125 (CA-125) levels at baseline, defined as a pre-treatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment
    • Participant has a performance status of 0 or 1 on the ECOG (Eastern Cooperative Oncology Group) Performance Scale
    • Participant must have adequate organ function
    • Participant has no history of a prior malignancy with the exception of cervical intraepithelial neoplasia, basal cell carcinoma of the skin, or has undergone potentially curative therapy with no evidence of that disease for five years, or is deemed at low risk for recurrence by his/her treating physician

Exclusion Criteria:

Parts A and B:

The participant:

  • Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks of entering the study
  • Has previously been treated with pegylated liposomal doxorubicin
  • Has active central nervous system metastases or a primary central nervous system tumor
  • Part A: Has had more than two prior chemotherapy regimens; in Part B, there is no limit to the number of prior chemotherapy regimens
  • Is known to be Human Immunodeficiency Virus (HIV) positive
  • Has a known history of Hepatitis B or C
  • Has a left ventricular ejection fraction (LVEF) below the institutional lower limit of normal
  • Has had prior doxorubicin exposure >240 mg/m^2 (or anthracycline equivalent)
  • Has initiated or adjusted bisphosphonate therapy/regimen within 30 days prior to Cycle 1 Day 1
  • Part B only: Has been previously treated with a poly[ADP] ribose polymerase (PARP) inhibitor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part A: MK-4827 + pegylated liposomal doxorubicin
MK-4827 and pegylated liposomal doxorubicin combination. Dose escalation/confirmation in participants with advanced solid tumors
Drug: MK-4827 + pegylated liposomal doxorubicin
Initial evaluation of a 16-day dosing schedule: A loading dose of MK-4827 will be administered orally on Days 1-2 of the cycle and a maintenance dose daily on Days 3-16. Pegylated liposomal doxorubicin 40 mg/m^2 will be administered intravenously on Day 3 of each cycle. The maintenance dose of MK-4827 will be escalated, until the maximum tolerated dose (MTD) is determined. If the maintenance dose is escalated above the loading dose, the loading dose will be escalated to a level equal to the maintenance dose, for the subsequent cycle. Other dosing schedules of MK-4827 may be explored, including 7-, 10-, 21- and 28-day schedules.
Other Names:
  • Doxil, Caelyx
Drug: MK-4827 + pegylated liposomal doxorubicin
MK-4827 will be administered according to one or two dose schedules as determined in Part A. Pegylated liposomal doxorubicin 40 mg/m^2 will be administered intravenously on Day 3 of the cycle.
Other Names:
  • Doxil, Caelyx
Experimental: Part B: MK-4827 + pegylated liposomal doxorubicin
MK-4827 and pegylated liposomal doxorubicin combination at 1 or 2 dose levels of MK-4827 to be determined from the results of Part A. Ovarian Cancer Cohort
Drug: MK-4827 + pegylated liposomal doxorubicin
Initial evaluation of a 16-day dosing schedule: A loading dose of MK-4827 will be administered orally on Days 1-2 of the cycle and a maintenance dose daily on Days 3-16. Pegylated liposomal doxorubicin 40 mg/m^2 will be administered intravenously on Day 3 of each cycle. The maintenance dose of MK-4827 will be escalated, until the maximum tolerated dose (MTD) is determined. If the maintenance dose is escalated above the loading dose, the loading dose will be escalated to a level equal to the maintenance dose, for the subsequent cycle. Other dosing schedules of MK-4827 may be explored, including 7-, 10-, 21- and 28-day schedules.
Other Names:
  • Doxil, Caelyx
Drug: MK-4827 + pegylated liposomal doxorubicin
MK-4827 will be administered according to one or two dose schedules as determined in Part A. Pegylated liposomal doxorubicin 40 mg/m^2 will be administered intravenously on Day 3 of the cycle.
Other Names:
  • Doxil, Caelyx

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame: 28 days (one cycle of treatment)
28 days (one cycle of treatment)
Tumor response rate
Time Frame: Every 8 weeks until disease progression
A tumor response is defined as a complete response, partial response, or a sustained decrease in tumor marker levels.
Every 8 weeks until disease progression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tesaro, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 25, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 19, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 18, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MK-4827-011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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