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

Swedish Medical Center

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Stage III Ovarian Cancer; Uterine Cancer; Stage IV Ovarian Cancer

Treatments: Drug: Olaparib; Drug: Carboplatin; Drug: Paclitaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01650376

ISS22810034

Details and patient eligibility

About

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.

Enrollment: 52 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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52 participants in 1 patient group

Olaparib plus carboplatin and paclitaxel

Experimental group

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Olaparib