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Trial record 28 of 2158 for:    doxorubicin

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01227941
Recruitment Status : Terminated
First Posted : October 25, 2010
Last Update Posted : October 19, 2016
Information provided by (Responsible Party):
Tesaro, Inc.

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: MK-4827 + pegylated liposomal doxorubicin Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2010
Actual Primary Completion Date : September 2011
Actual Study Completion Date : September 2011

Arm Intervention/treatment
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 Name: 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
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 Name: Doxil, Caelyx

Primary Outcome Measures :
  1. Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: 28 days (one cycle of treatment) ]
  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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Responsible Party: Tesaro, Inc. Identifier: NCT01227941     History of Changes
Other Study ID Numbers: MK-4827-011
First Posted: October 25, 2010    Key Record Dates
Last Update Posted: October 19, 2016
Last Verified: March 2012
Keywords provided by Tesaro, Inc.:
advanced solid tumors
ovarian cancer
pegylated liposomal doxorubicin
Additional relevant MeSH terms:
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Liposomal doxorubicin
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors