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Olaparib Maintenance in Patients With MCRPC After Docetaxel Treatment Reaching Partial or Stable Response (IMANOL) (IMANOL)

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ClinicalTrials.gov Identifier: NCT03434158
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : February 7, 2019
Sponsor:
Collaborators:
AstraZeneca
Apices Soluciones S.L.
Information provided by (Responsible Party):
Spanish Oncology Genito-Urinary Group

Brief Summary:

A number of important systemic therapies have been developed to treat mCRPC and have received regulatory approval and now comprise the current therapeutic landscape. Durable and complete response following first-line chemotherapy in patients with advanced PC are uncommon. Most patients will ultimately experience disease progression within 6-9 months after initial response. Optimal Second line therapy in mCRPC is not well established and several options are possible.

Olaparib has demonstrated anti-tumour activity in non-comparative studies in patients with germline BReast CAncer gene (gBRCA) mutated cancers including ovarian, breast, pancreas and prostate. Olaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed Breast Cancer gene-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

This phase II study is developed to assess the effect of maintenance treatment with olaparib on radiologic progression free survival (rPFS) in patients with mCRPC who have received at least 6 cycles of docetaxel and achieved partial or complete response or disease stabilization according RECIST 1.1 criteria and PCWG3.


Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: Olaparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial Evaluating Olaparib Maintenance in Patients With MCRPC After Docetaxel Treatment Reaching Partial or Stable Response.
Actual Study Start Date : February 6, 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Olaparib
600 mg/day
Drug: Olaparib
300 mg twice a day
Other Name: Lynparza




Primary Outcome Measures :
  1. Radiographic progression free survival (rPFS) [ Time Frame: Up to 1 year ]
    Time from treatment with olaparib to the date of first disease radiographic progression or death for any reason. Radiographic progression disease will be evaluated according RECIST 1.1 criteria and PCWG3


Secondary Outcome Measures :
  1. PSA progression free survival (PSA PFS) [ Time Frame: Up to 1 year ]
    Time from treatment with olaparib to the date of first PSA progression (according PWCG3 criteria) or death for any reason.

  2. Clinical PFS [ Time Frame: Up to 1 year ]
    Time from treatment with olaparib to the date of first clinical progression (significant pain increase or clinical deterioration that requires initiating another line of treatment) or death for any reason.

  3. Radiologic response rate [ Time Frame: Up to 1 year ]
    Radiographic response will be evaluated according RECIST 1.1.

  4. PSA response rate [ Time Frame: Up to 1 year ]
    PSA response is a reduction in serum PSA concentration of ≥50% from baseline.

  5. Number of individual events (hematologic events and not hematologic events) [ Time Frame: Up to 1 year ]
    Number of events per patient


Other Outcome Measures:
  1. Gene mutation(s) [ Time Frame: At Baseline ]
    Number of gene mutation/s



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Histologically confirmed prostate adenocarcinoma.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of informed consent prior to any study specific procedures. For inclusion in the study patients must provide the informed consent also for genetic research. Genetic counselling for patients with germline mutation in any of the Homologous Recombination Repair genes should be performed.
  • Male patients, who must be ≥18 years of age.
  • Histologically confirmed prostate adenocarcinoma.
  • Patients must have metastatic disease before starting treatment with docetaxel (metastatic disease documented by positive bone scan or metastatic lesions on CT, MRI).
  • No prior exposure to platinum, cyclophosphamide, mitoxantrone or Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitors.
  • No cancer progression on the basis of Prostate Cancer Working Group (PCWG3) criteria to docetaxel therapy.
  • Completed at least six cycles and a maximum of ten cycles of chemotherapy containing docetaxel.
  • Patients are allowed to have received up to two lines for mCRPC before chemotherapy (abiraterone, enzalutamide or radium 223).
  • Documented germline/somatic mutation in any of the Homologous Recombination Repair genes, including among others, BRCA1 or BRCA2, ATM, Fanconi genes, CHEK2, mutL homolog 1 (MLH1), mutS homologue 2 (MSH2), mutS homolog 6 (MSH6), PMS2, PALB2, RAD51C, MRE11 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
  • 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 with no blood transfusion in the past 28 days.
    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    • Platelet count ≥ 100 x 109/L.
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
    • Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase ((SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN.
    • Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min:

Estimated creatinine clearance = ((140-age [years]) x weight (kg) (x F)^a) / serum creatinine (mg/dL) x 72 F=1 for males.

  • *Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  • Patients must be able to take oral medication.
  • *Patients must have a life expectancy ≥ 16 weeks.
  • Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination [see appendix A for acceptable methods], throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central testing. If there is not written confirmation of the availability of an archived tumour sample prior to enrolment the patient is not eligible for the study.

Exclusion Criteria:

  • Involvement in the planning and/or conduct of the study (applies to AstraZeneca or sponsor staff and/or staff at the study site).
  • Previous inclusion in the present study.
  • Participation in another clinical study with an investigational product during the last month.
  • Any previous treatment with PARP inhibitor, including olaparib.
  • Patients who do not have deleterious or suspected deleterious Homologous Recombination Repair genes mutations and only have Homologous Recombination Repair genes mutations that are considered to be non-detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favour polymorphism" or "benign polymorphism" etc.).
  • Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
  • 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.
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia and nail toxicity.
  • Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
  • 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 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  • Major surgery within 4 weeks 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, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial 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.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03434158


Contacts
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Contact: Macarena Cruz Navas 0034671422325 projectmanager@sogug.es

Locations
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Spain
Complexo Hospitalario Universitario de Santiago Recruiting
Santiago De Compostela, A Coruña, Spain, 15706
Contact: Urbano Anido, MD    0034981950511    urbanoanido@gmail.com   
Hospital Universitario Central de Asturias Recruiting
Oviedo, Asturias, Spain, 33011
Contact: Carlos Álvarez, MD    0034985108000    carlos.alvfer@gmail.com   
ICO L'Hospitalet Recruiting
L'Hospitalet De Llobregat, Barcelona, Spain, 08908
Contact: Lucía Heras, MD    0034932607822    lheras@iconcologia.net   
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Begoña Mellado, MD    0034932275400 ext 3297    bmellado@clinic.ub.es   
Complejo Hospitalario Regional Reina Sofía Recruiting
Córdoba, Spain, 14004
Contact: María J Méndez, MD    0034957011464    mjosemv@yahoo.es   
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: José M Sepulveda, MD    0034913908546    jmsepulveda76@gmail.com   
Fundación Instituto Valenciano de Oncología Recruiting
Valencia, Spain, 46009
Contact: María J Juan Fita, MD    0034961104606    mjuanfi81@hotmail.com   
Hospital Universitario i Politècnic La Fe Recruiting
Valencia, Spain, 46026
Contact: David Lorente, MD    0034961244000    davlorente@hotmail.com   
Sponsors and Collaborators
Spanish Oncology Genito-Urinary Group
AstraZeneca
Apices Soluciones S.L.
Investigators
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Principal Investigator: María J Juan Fita, MD Fundación Instituto Valenciano de Oncología

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Responsible Party: Spanish Oncology Genito-Urinary Group
ClinicalTrials.gov Identifier: NCT03434158     History of Changes
Other Study ID Numbers: SOGUG-2016-A-IEC(PRO)-12
2017-001469-26 ( EudraCT Number )
First Posted: February 15, 2018    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Spanish Oncology Genito-Urinary Group:
Metastatic Prostate Cancer Resistant to Castration

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Olaparib
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors