Resistant Ovarian Cancer, Olaparib and Liposomal Doxorubicin

NCT ID: NCT03161132

Last Updated: 2023-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-13
• Study Completion Date: 2022-12-31

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.

Detailed Description

The combination of Poly (ADP-ribose) polymerase (PARP) inhibitors with PLD may provide a synergistic effect in patients with advanced ovarian cancer, especially those with Homologous recombination deficiency (HRD), because of the decreased ability to repair chemotherapy-induced DNA damage. Preclinical studies with PARP inhibitors have shown potentiation of the cytotoxic effects of chemotherapeutic agents and a recent phase I study has shown the tolerability of the combination and efficacy in recurrent ovarian cancer. In this study, encouraging efficacy results were seen in ovarian cancer patients and were not limited by Germline BRCA1/2 (gBRCA) Mutations status or sensitivity to platinum therapy.

Conditions

Advanced Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olaparib 300mg

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.

Group Type: EXPERIMENTAL

Olaparib

Intervention Type: DRUG

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

Pegylated Liposomal Doxorubicin (PLD)

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

Group Type: OTHER

Pegylated Liposomal Doxorubicin

Intervention Type: DRUG

PLD 40mg/m2 every 28 days intravenous

Interventions

Olaparib

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

Intervention Type: DRUG

Pegylated Liposomal Doxorubicin

PLD 40mg/m2 every 28 days intravenous

Intervention Type: DRUG

Other Intervention Names

Lynparza; PLD

Eligibility Criteria

Inclusion Criteria

• 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 with histological or cytological confirmed high grade serous or endometrioid epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer and resistant platinum relapse with no prior treatment with PLD for their resistant relapse. Previous treatment with PLD is allowed as long as it was part of one platinum based regimen and the treatment was finalized at least six months previously to inclusion in this trial.
• 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%.

Exclusion Criteria

• 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.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Breast feeding women.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
• Patients with known active hepatic disease (i.e., Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
• Patients with a known hypersensitivity to the combination/comparator agent
• Patients with uncontrolled seizures.
• Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Grupo Español de Investigación en Cáncer de Ovario

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alejandro Pérez-Fidalgo, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Valencia, Hospital Clinico Universitario de Valencia

Locations

Corporación Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas de Gran Canaria, Gran Canaria, Spain

Hospital Son Llatzer

Palma de Mallorca, Mallorca, Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Countries

Spain

References

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.

Reference Type: BACKGROUND

PMID: 30820349 (View on PubMed)

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.

Reference Type: RESULT

PMID: 34329939 (View on PubMed)

Other Identifiers

2016-004850-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEICO-1601

Identifier Type: -

Identifier Source: org_study_id