Clinical Trials /

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

NCT03434158

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Olaparib Maintenance in Patients With MCRPC After Docetaxel Treatment Reaching Partial or Stable Response (IMANOL)
  • Official Title: Phase II Trial Evaluating Olaparib Maintenance in Patients With MCRPC After Docetaxel Treatment Reaching Partial or Stable Response.

Clinical Trial IDs

  • ORG STUDY ID: SOGUG-2016-A-IEC(PRO)-12
  • NCT ID: NCT03434158

Conditions

  • Prostate Cancer Metastatic

Interventions

DrugSynonymsArms
OlaparibLynparzaOlaparib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
OlaparibExperimental600 mg/day
  • Olaparib

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiographic progression free survival (rPFS)
Time Frame:Up to 1 year
Safety Issue:
Description: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

Measure:PSA progression free survival (PSA PFS)
Time Frame:Up to 1 year
Safety Issue:
Description:Time from treatment with olaparib to the date of first PSA progression (according PWCG3 criteria) or death for any reason.
Measure:Clinical PFS
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Radiologic response rate
Time Frame:Up to 1 year
Safety Issue:
Description:Radiographic response will be evaluated according RECIST 1.1.
Measure:PSA response rate
Time Frame:Up to 1 year
Safety Issue:
Description:PSA response is a reduction in serum PSA concentration of ≥50% from baseline.
Measure:Number of individual events (hematologic events and not hematologic events)
Time Frame:Up to 1 year
Safety Issue:
Description:Number of events per patient

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Spanish Oncology Genito-Urinary Group

Trial Keywords

  • Metastatic Prostate Cancer Resistant to Castration

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