Resistant Ovarian Cancer, Olaparib and Liposomal Doxorubicin

NCT03161132 | Completed Phase 2 DMC

• 2 other identifiers: GEICO-16012016-004850-14
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 8

Brief Summary

Impact of the combination of Olaparib and Pegylated Liposomal Doxorubicin on improvement of progression-free survival at 6 months in patients with platinum resistant advanced ovarian cancer.

Conditions

Advanced Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Proportion of pacients with no progression of disease at 6 months after start of treatment with Olaparib plus PLD

  6 months

Secondary Outcomes (7)

• Objective Response Rate

  20 months

• Disease Control Rate

  20 months

• Response to treatment Rate according CA-125 levels

  20 months

• Progression-free survival

  20 months

• Overall survival

  20 months

Other Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  20 months

• DNA damage

  20 months

Study Arms (2)

Olaparib 300mg

EXPERIMENTAL

Olaparib bid orally at 300 mg (tablet formulation) continuously, combined with chemotherapy with Pegylated Liposomal Doxorubicin (up to 6 cycles), then, as monotherapy at the same dose and frequency (300mg bid orally) until progression of disease or unaccepted toxicity.

Drug: Olaparib

Pegylated Liposomal Doxorubicin (PLD)

OTHER

PLD 40mg/m2 every 28 days intravenous for up to 6 cycles. This treatment will be combined with Olaparib (as described earlier).

Drug: Pegylated Liposomal Doxorubicin

Interventions

Olaparib DRUG

Combination of continous olaparib 300mg for oral administration plus Pegylated Liposomal Doxorubicin (PLD), followed by maintenance treatment further described.

Also known as: Lynparza

Olaparib 300mg

Pegylated Liposomal Doxorubicin DRUG

PLD 40mg/m2 every 28 days intravenous

Also known as: PLD

Pegylated Liposomal Doxorubicin (PLD)

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures. Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and those obtained prior to signing of informed consent may be utilized for screening or for baseline purposes provided these procedures are conducted as specified in the protocol.
• Patients must have platinum-resistant disease, defined as progression within \<6 months from completion of at least 4 cycles of platinum and up to 3 prior chemotherapy regimens. Patients should have documented treatment-free interval of ≥6 months following 1st chemotherapy regimen received. Patients with a deleterious mutation in BRCA are eligible in any case with a resistant relapse including primary resistant relapse.
• Have measurable disease as defined by RECIST v1.1 Criteria. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Female patients with \> 18 years of age.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: Haemoglobin ≥ 10.0 g/dL; Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; No features suggestive of Myelodysplastic Syndrome/Acute Myeloid Leukemia on peripheral blood smear; White blood cells (WBC) \> 3x109/L; Platelet count ≥ 100 x 109/L; Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); aspartate aminotransferase (AST/SGOT)/Alaninotransferase (ALT/SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN.
• Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min. PLD is metabolised by the liver and excreted in the bile. Population pharmacokinetic data (in the range of creatinine clearance tested of 30-156 ml/min) demonstrate that PLD clearance is not influenced by renal function. No pharmacokinetic data are available in patients with creatinine clearance of less than 30 ml/min.
• Patients must have a life expectancy ≥ 16 weeks.
• Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 Postmenopausal is defined as: Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments; luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50; Radiation-induced oophorectomy with last menses \>1 year ago; Chemotherapy-induced menopause with \>1 year interval since last menses; or surgical sterilisation (bilateral oophorectomy or hysterectomy).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
• Left Ventricular Ejection Fraction (LVEF) ≥ 50%.

You may not qualify if:

• Platinum-refractory disease (progression during previous platinum therapy).
• Involvement in the planning and/or conduct of the study (applies to both Sponsor staff and/or staff at the study site).
• Previous enrolment in the present study.
• Participation in another clinical study with an investigational product during the last 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment.
• Any previous treatment with a PARP inhibitor, including olaparib.
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥5 years.
• Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
• Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
• Persistent toxicities (\>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
• Resting ECG with corrected QT interval (QTc) \>470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Blood transfusions within 28 days prior to study entry.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
• Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on high-resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.

Sponsors & Collaborators

• Grupo Español de Investigación en Cáncer de Ovario: lead
• AstraZeneca: collaborator

Study Sites (8)

Corporación Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas de Gran Canaria, Gran Canaria, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Mallorca, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Related Publications (2)

• Perez-Fidalgo JA, Iglesias M, Bohn U, Calvo E, Garcia Y, Guerra E, Manso L, Santaballa A, Gonzalez-Martin A. GEICO1601-ROLANDO: a multicentric single arm Phase II clinical trial to evaluate the combination of olaparib and pegylated liposomal doxorubicin for platinum-resistant ovarian cancer. Future Sci OA. 2019 Jan 10;5(2):FSO370. doi: 10.4155/fsoa-2018-0107. eCollection 2019 Feb.

  PMID: 30820349 BACKGROUND

• Perez-Fidalgo JA, Cortes A, Guerra E, Garcia Y, Iglesias M, Bohn Sarmiento U, Calvo Garcia E, Manso Sanchez L, Santaballa A, Oaknin A, Redondo A, Rubio MJ, Gonzalez-Martin A. Olaparib in combination with pegylated liposomal doxorubicin for platinum-resistant ovarian cancer regardless of BRCA status: a GEICO phase II trial (ROLANDO study). ESMO Open. 2021 Aug;6(4):100212. doi: 10.1016/j.esmoop.2021.100212. Epub 2021 Jul 27.

  PMID: 34329939 RESULT

MeSH Terms

Interventions

olaparib; liposomal doxorubicin; 1-dodecylpyridoxal

Study Officials

• Alejandro Pérez-Fidalgo, M.D., Ph.D.

  University of Valencia, Hospital Clinico Universitario de Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentric

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: May 19, 2017
• Study Start: December 13, 2017
• Primary Completion: February 7, 2020
• Study Completion: December 31, 2022
• Last Updated: January 27, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8)