Phase Ib Study of Olaparib Plus Weekly Carboplatin and Paclitaxel in Relapsed Ovarian Cancer

March 21, 2018 updated by: Swedish Medical Center

Phase Ib With Expansion of Patients at the MTD Study of Olaparib Plus Weekly (Metronomic) Carboplatin and Paclitaxel in Relapsed Ovarian Cancer Patients

The purpose of this study is to determine the maximum tolerated dose (MTD) of the investigational agent, olaparib, to give in combination with carboplatin and paclitaxel in patients with relapsed ovarian cancer or uterine cancer. Furthermore, the investigators intend to study the safety and tolerability of the study treatment, response to treatment, time to disease progression, and overall survival.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

52

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Edmonds, Washington, United States, 98026
        • Swedish Cancer Institute Edmonds Campus
      • Issaquah, Washington, United States, 98029
        • Swedish Cancer Institute Issaquah Campus
      • Seattle, Washington, United States, 98104
        • Pacific Gynecology Specialists
      • Seattle, Washington, United States, 98104
        • Swedish Medical Center Cancer Institute
      • Seattle, Washington, United States, 98107
        • Swedish Cancer Institute Ballard Campus

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Advanced (stage III or IV), histologically or cytologically documented ovarian cancer or serious uterine cancer patients who relapsed after primary therapy with a platinum and a taxane. This includes:

    • Platinum sensitive: relapsed at least 6 months following platinum treatment
    • Platinum refractory: the cancer grew while on platinum treatment
    • Platinum resistant: recurrence within 6 months of platinum treatment
  • Must have failed first line treatment
  • ECOG performance status 0-2
  • Must be able to swallow and retain oral medication
  • Life expectancy greater than 16 weeks

  • Must have normal organ and bone marrow function defined as follows:

    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
    • White blood cells (WBC) > 3 x 10^9/L
    • Platelet count ≥ 100 10^9/L
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal
    • AST (SGOT)/ALT (SGPT) ≤ x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5 ULN
    • Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

Exclusion Criteria:

  • Any previous treatment with a PARP inhibitor, including olaparib
  • Any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or longer period depending on the defined characteristics of the agents used)
  • Currently receiving the following classes of inhibitors of CYP3A4: azole antifungals, macrolide antibiotics, and protease inhibitors
  • Second primary cancer except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
  • Symptomatic uncontrolled brain metastases
  • Major surgery within 2 weeks of starting study treatment
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
  • Known active hepatic disease (i.e. Hepatitis B or C)
  • Uncontrolled seizures
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin or paclitaxel

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Olaparib plus carboplatin and paclitaxel
Drug: Olaparib
Olaparib will be administered orally on Days 1, 2, and 3 of each week until DLT or disease progression. A minimum of 3 patients will be enrolled into each cohort. The anticipated dose escalation sequence of olaparib is 50, 100, 150 and 200 mg, taken twice a day will be used.
Other Names:
  • AZD 2281
  • AZD-2281
  • AZD2281
Drug: Carboplatin
AUC 2 weekly for 3 weeks of a 4 week cycle. For patients who experience a complete response, the carboplatin and paclitaxel will be discontinued and olaparib monotherapy (400 mg, taken twice a day) will continue until disease progression and as long as the investigator feels they are benefiting from the treatment.
Other Names:
  • Paraplatin
  • Paraplatin NovaPlus
Drug: Paclitaxel
60mg/m2 weekly for 3 weeks of a 4 week cycle. For patients who experience a complete response, the carboplatin and paclitaxel will be discontinued and olaparib monotherapy (400 mg, taken twice a day) will continue until disease progression and as long as the investigator feels they are benefiting from the treatment.
Other Names:
  • Taxol
  • Nov-Onxol
  • Onxol
  • Paclitaxel Novaplus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Dose Limiting Toxicity (DLT)
Time Frame: 1 cycle (1 cycle = 28 days)
1 cycle (1 cycle = 28 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of Reported Adverse Events
Time Frame: Weekly assessments of clinical and laboratory values, and vital sign measurements performed while receiving study treatment. (Anticipated time of 6 months)
Weekly assessments of clinical and laboratory values, and vital sign measurements performed while receiving study treatment. (Anticipated time of 6 months)

Other Outcome Measures

Outcome Measure
Time Frame
Response to Therapy
Time Frame: Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Time to Progression
Time Frame: Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Overall Survival
Time Frame: Following the last treatment, patient's condition will be monitored every 3 months until death.
Following the last treatment, patient's condition will be monitored every 3 months until death.

Collaborators and Investigators

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

Sponsor

Swedish Medical Center

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Saul Rivkin, MD, Swedish Medical Center Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

August 1, 2012

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

July 18, 2012

First Submitted That Met QC Criteria

July 23, 2012

First Posted (Estimate)

July 26, 2012

Study Record Updates

Last Update Posted (Actual)

March 23, 2018

Last Update Submitted That Met QC Criteria

March 21, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISS22810034

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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