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

Swedish Medical Center52 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Stage III Ovarian Cancer Stage IV Ovarian Cancer Uterine Cancer

Interventions

OlaparibDRUG

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.

CarboplatinDRUG

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.

PaclitaxelDRUG

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.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

Swedish Cancer Institute Edmonds Campus

Edmonds, Washington, United States

Swedish Cancer Institute Issaquah Campus

Issaquah, Washington, United States

Pacific Gynecology Specialists

Seattle, Washington, United States

Swedish Medical Center Cancer Institute

Seattle, Washington, United States

Outcomes

Primary Outcomes

Incidence of Dose Limiting Toxicity (DLT)

Time frame: 1 cycle (1 cycle = 28 days)

Secondary Outcomes

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)

Data from ClinicalTrials.gov

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