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

Uterine Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01650376
• Other study ID #: ISS22810034
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: July 18, 2012
• Last updated: March 21, 2018
• Start date: August 2012
• Est. completion date: December 2019

Study information

• Verified date: February 2018
• Source: Swedish Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ovarian Neoplasms
• Stage III Ovarian Cancer
• Stage IV Ovarian Cancer
• Uterine Cancer
• Uterine Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	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 Cancer Institute Ballard Campus	Seattle	Washington
United States	Swedish Medical Center Cancer Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Medical Center	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Response to Therapy		Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Other	Time to Progression		Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
Other	Overall Survival		Following the last treatment, patient's condition will be monitored every 3 months until death.
Primary	Incidence of Dose Limiting Toxicity (DLT)		1 cycle (1 cycle = 28 days)
Secondary	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)