Clinical trial NCT01650376: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Stage III Ovarian Cancer
Stage IV Ovarian Cancer
Uterine Cancer
Keywords: Ovarian Neoplasms
Cancer of the Ovary
Ovarian Cancer
Uterine Neoplasms
Cancer of the Uterus
Uterine Cancer
Olaparib
AZD2281
Carboplatin
Paclitaxel
Relapsed
Lead sponsor: Swedish Medical Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2012-07-26
Enrollment: 52
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicity (DLT)
timeFrame: 1 cycle (1 cycle = 28 days)
Secondary outcomes:
measure: Number of Reported Adverse Events
timeFrame: Weekly assessments of clinical and laboratory values, and vital sign measurements performed while receiving study treatment. (Anticipated time of 6 months)
Other outcomes:
measure: Response to Therapy
timeFrame: Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
measure: Time to Progression
timeFrame: Measured by CT scans performed every 8 weeks while receiving treatment. (Anticipated time of 6 months)
measure: Overall Survival
timeFrame: Following the last treatment, patient's condition will be monitored every 3 months until death.
Locations:
city: Edmonds
country: United States
facility: Swedish Cancer Institute Edmonds Campus
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute Issaquah Campus
state: Washington
city: Seattle
country: United States
facility: Pacific Gynecology Specialists
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute Ballard Campus
state: Washington
Study officials:
affiliation: Swedish Medical Center Cancer Institute
name: Saul Rivkin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.