search
Back to results

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

Primary Purpose

Stage III Ovarian Cancer, Stage IV Ovarian Cancer, Uterine Cancer

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Olaparib
Carboplatin
Paclitaxel
Sponsored by
Swedish Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Ovarian Cancer focused on measuring Ovarian Neoplasms, Cancer of the Ovary, Ovarian Cancer, Uterine Neoplasms, Cancer of the Uterus, Uterine Cancer, Olaparib, AZD2281, Carboplatin, Paclitaxel, Relapsed

Eligibility Criteria

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

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

Sites / Locations

  • Swedish Cancer Institute Edmonds Campus
  • Swedish Cancer Institute Issaquah Campus
  • Pacific Gynecology Specialists
  • Swedish Medical Center Cancer Institute
  • Swedish Cancer Institute Ballard Campus

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Olaparib plus carboplatin and paclitaxel

Arm Description

Outcomes

Primary Outcome Measures

Incidence of Dose Limiting Toxicity (DLT)

Secondary Outcome Measures

Number of Reported Adverse Events

Full Information

First Posted
July 18, 2012
Last Updated
March 21, 2018
Sponsor
Swedish Medical Center
Collaborators
AstraZeneca
search

1. Study Identification

Unique Protocol Identification Number
NCT01650376
Brief Title
Phase Ib Study of Olaparib Plus Weekly Carboplatin and Paclitaxel in Relapsed Ovarian Cancer
Official Title
Phase Ib With Expansion of Patients at the MTD Study of Olaparib Plus Weekly (Metronomic) Carboplatin and Paclitaxel in Relapsed Ovarian Cancer Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2012 (Actual)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swedish Medical Center
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Ovarian Cancer, Stage IV Ovarian Cancer, Uterine Cancer
Keywords
Ovarian Neoplasms, Cancer of the Ovary, Ovarian Cancer, Uterine Neoplasms, Cancer of the Uterus, Uterine Cancer, Olaparib, AZD2281, Carboplatin, Paclitaxel, Relapsed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Olaparib plus carboplatin and paclitaxel
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
AZD-2281, AZD2281, AZD 2281
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin, Paraplatin NovaPlus
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol, Onxol, Nov-Onxol, Paclitaxel Novaplus
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicity (DLT)
Time Frame
1 cycle (1 cycle = 28 days)
Secondary Outcome Measure Information:
Title
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)
Other Pre-specified Outcome Measures:
Title
Response to Therapy
Time Frame
Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Title
Time to Progression
Time Frame
Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Title
Overall Survival
Time Frame
Following the last treatment, patient's condition will be monitored every 3 months until death.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saul Rivkin, MD
Organizational Affiliation
Swedish Medical Center Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Swedish Cancer Institute Edmonds Campus
City
Edmonds
State/Province
Washington
ZIP/Postal Code
98026
Country
United States
Facility Name
Swedish Cancer Institute Issaquah Campus
City
Issaquah
State/Province
Washington
ZIP/Postal Code
98029
Country
United States
Facility Name
Pacific Gynecology Specialists
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Swedish Medical Center Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Swedish Cancer Institute Ballard Campus
City
Seattle
State/Province
Washington
ZIP/Postal Code
98107
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30700568
Citation
Rivkin SE, Moon J, Iriarte DS, Bailey E, Sloan HL, Goodman GE, BonDurant AE, Velijovich D, Wahl T, Jiang P, Shah CA, Drescher C, Fer MF, Kaplan HG, Ellis ED. Phase Ib with expansion study of olaparib plus weekly (Metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients. Int J Gynecol Cancer. 2019 Feb;29(2):325-333. doi: 10.1136/ijgc-2018-000035. Epub 2019 Jan 29.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs