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

Primary Purpose

Ovarian Cancer

Status

Terminated

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

MK-4827 + pegylated liposomal doxorubicin

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring advanced solid tumors, ovarian cancer, pegylated liposomal doxorubicin, Doxil, Caelyx

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part A: MK-4827 + pegylated liposomal doxorubicin

Part B: MK-4827 + pegylated liposomal doxorubicin

Arm Description

MK-4827 and pegylated liposomal doxorubicin combination. Dose escalation/confirmation in participants with advanced solid tumors

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

Outcomes

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLTs)

Tumor response rate

A tumor response is defined as a complete response, partial response, or a sustained decrease in tumor marker levels.

Secondary Outcome Measures

Full Information

NCT ID

NCT01227941

First Posted

October 22, 2010

Last Updated

October 18, 2016

Sponsor

Tesaro, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01227941

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Terminated

Study Start Date

November 2010 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tesaro, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Cancer

Keywords

advanced solid tumors, ovarian cancer, pegylated liposomal doxorubicin, Doxil, Caelyx

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: MK-4827 + pegylated liposomal doxorubicin

Arm Type

Experimental

Arm Description

MK-4827 and pegylated liposomal doxorubicin combination. Dose escalation/confirmation in participants with advanced solid tumors

Arm Title

Part B: MK-4827 + pegylated liposomal doxorubicin

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

MK-4827 + pegylated liposomal doxorubicin

Other Intervention Name(s)

Doxil, Caelyx

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

MK-4827 + pegylated liposomal doxorubicin

Other Intervention Name(s)

Doxil, Caelyx

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants with Dose-limiting Toxicities (DLTs)

Time Frame

28 days (one cycle of treatment)

Title

Tumor response rate

Description

A tumor response is defined as a complete response, partial response, or a sustained decrease in tumor marker levels.

Time Frame

Every 8 weeks until disease progression

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

12. IPD Sharing Statement

Learn more about this trial

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

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