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

• ClinicalTrials.gov Identifier: NCT01650376
• Recruitment Status: Unknown
• First Posted: July 26, 2012
• Last Update Posted: March 23, 2018
• Sponsor: Swedish Medical Center
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Swedish Medical Center

Tracking Information

• First Submitted Date: July 18, 2012
• First Posted Date: July 26, 2012
• Last Update Posted Date: March 23, 2018
• Actual Study Start Date: August 2012
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 23, 2012): Incidence of Dose Limiting Toxicity (DLT) [ Time Frame: 1 cycle (1 cycle = 28 days) ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: July 23, 2012): 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) ]
• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 23, 2012)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Phase Ib Study of Olaparib Plus Weekly Carboplatin and Paclitaxel in Relapsed Ovarian Cancer
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

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.
  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

Study Arms

Experimental: Olaparib plus carboplatin and paclitaxel

Interventions:

• Drug: Olaparib
• Drug: Carboplatin
• Drug: Paclitaxel

• Publications *: Rivkin SE, Moon J, Iriarte DS, Bailey E, Sloan HL, Goodman GE, BonDurant AE, Velijovich D, Wahl T, Jiang P, Shah CA, Drescher C, Fer MF, Kaplan HG, Ellis ED. Phase Ib with expansion study of olaparib plus weekly (Metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients. Int J Gynecol Cancer. 2019 Feb;29(2):325-333. doi: 10.1136/ijgc-2018-000035. Epub 2019 Jan 29.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 23, 2012): 52
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2019
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01650376
• Other Study ID Numbers: ISS22810034
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Swedish Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Swedish Medical Center
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

• Principal Investigator: Saul Rivkin, MD; Swedish Medical Center Cancer Institute

• PRS Account: Swedish Medical Center
• Verification Date: February 2018