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

Sponsor

Swedish Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT01650376

Collaborator

AstraZeneca (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

10.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Aug 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

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 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

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

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

Outcome Measures

Primary Outcome Measures

Incidence of Dose Limiting Toxicity (DLT) [1 cycle (1 cycle = 28 days)]

Secondary Outcome Measures

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)]

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Swedish Cancer Institute Edmonds Campus	Edmonds	Washington	United States	98026
2	Swedish Cancer Institute Issaquah Campus	Issaquah	Washington	United States	98029
3	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
4	Swedish Medical Center Cancer Institute	Seattle	Washington	United States	98104
5	Swedish Cancer Institute Ballard Campus	Seattle	Washington	United States	98107