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

NCT01650376 | Unknown Phase 1

• 1 other identifier: ISS22810034
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicity (DLT)

  1 cycle (1 cycle = 28 days)

Secondary Outcomes (1)

• 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 Outcomes (3)

• 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.

Study Arms (1)

Olaparib plus carboplatin and paclitaxel

EXPERIMENTAL

Drug: Olaparib; Drug: Carboplatin; Drug: Paclitaxel

Interventions

Olaparib DRUG

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.

Also known as: AZD-2281, AZD2281, AZD 2281

Olaparib plus carboplatin and paclitaxel

Carboplatin DRUG

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.

Also known as: Paraplatin, Paraplatin NovaPlus

Olaparib plus carboplatin and paclitaxel

Paclitaxel DRUG

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.

Also known as: Taxol, Onxol, Nov-Onxol, Paclitaxel Novaplus

Olaparib plus carboplatin and paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swedish Medical Center: lead
• AstraZeneca: collaborator

Study Sites (5)

Swedish Cancer Institute Edmonds Campus

Edmonds, Washington, 98026, United States

Location

Swedish Cancer Institute Issaquah Campus

Issaquah, Washington, 98029, United States

Location

Pacific Gynecology Specialists

Seattle, Washington, 98104, United States

Location

Swedish Medical Center Cancer Institute

Seattle, Washington, 98104, United States

Location

Swedish Cancer Institute Ballard Campus

Seattle, Washington, 98107, United States

Location

Related Publications (1)

• 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.

  PMID: 30700568 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Uterine Neoplasms; Recurrence

Interventions

olaparib; Carboplatin; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Saul Rivkin, MD

  Swedish Medical Center Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 26, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: March 23, 2018

Record last verified: 2018-02

Locations

US (5)