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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Swedish Medical Center
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Swedish Medical Center
ClinicalTrials.gov Identifier:
NCT01650376
First received: July 18, 2012
Last updated: July 23, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Stage III Ovarian Cancer
Stage IV Ovarian Cancer
Uterine Cancer
Drug: Olaparib
Drug: Carboplatin
Drug: Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Swedish Medical Center:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicity (DLT) [ Time Frame: 1 cycle (1 cycle = 28 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Response to Therapy [ Time Frame: Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months) ] [ Designated as safety issue: Yes ]
  • Time to Progression [ Time Frame: Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months) ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Following the last treatment, patient's condition will be monitored every 3 months until death. ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: August 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • AZD2281
  • AZD 2281
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
  • Onxol
  • Nov-Onxol
  • Paclitaxel Novaplus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01650376

Contacts
Contact: Barry Boatman, RN, MA, OCN (206) 215-3086 CancerResearch@Swedish.org

Locations
United States, Washington
Swedish Medical Center Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Barry Boatman, RN, MA, OCN    206-215-3086    CancerResearch@Swedish.org   
Principal Investigator: Saul Rivkin, MD         
Sponsors and Collaborators
Swedish Medical Center
AstraZeneca
Investigators
Principal Investigator: Saul Rivkin, MD Swedish Medical Center Cancer Institute
  More Information

No publications provided

Responsible Party: Swedish Medical Center
ClinicalTrials.gov Identifier: NCT01650376     History of Changes
Other Study ID Numbers: ISS22810034
Study First Received: July 18, 2012
Last Updated: July 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Swedish Medical Center:
Ovarian Neoplasms
Cancer of the Ovary
Ovarian Cancer
Uterine Neoplasms
Cancer of the Uterus
Uterine Cancer
Olaparib
AZD2281
Carboplatin
Paclitaxel
Relapsed

Additional relevant MeSH terms:
Ovarian Neoplasms
Uterine Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 26, 2014