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

Study Overview
=================
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.

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

Conditions
-----------------
Stage III Ovarian Cancer, Stage IV Ovarian Cancer, Uterine Cancer

Intervention / Treatment
-----------------
* Drug: Olaparib
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olaparib plus carboplatin and paclitaxel<br> | Drug: Olaparib<br>* 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.<br>* Other names: AZD 2281;Drug: Carboplatin<br>* 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.<br>* Other names: Paraplatin NovaPlus;Drug: Paclitaxel<br>* 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.<br>* Other names: Paclitaxel Novaplus;|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ovarian Neoplasms, Cancer of the Ovary, Ovarian Cancer, Uterine Neoplasms, Cancer of the Uterus, Uterine Cancer, Olaparib, AZD2281, Carboplatin, Paclitaxel, Relapsed