Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate PM01183 in Combination With Olaparib in Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02684318
Recruitment Status : Unknown
Verified June 2017 by Poveda, Andrés, M.D..
Recruitment status was:  Recruiting
First Posted : February 18, 2016
Last Update Posted : June 22, 2017
Sponsor:
Collaborators:
AstraZeneca
PharmaMar
Information provided by (Responsible Party):
Poveda, Andrés, M.D.

Brief Summary:
Phase Ib/II study to evaluate the efficacy and tolerability of PM01183 in combination with olaparib in patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Cancer Ovarian Cancer Endometrial Cancer Breast Cancer Drug: PM01183 + olaparib Phase 1 Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/II Study to Evaluate the Efficacy and Tolerability of PM01183 in Combination With Olaparib in Patients With Advanced Solid Tumors
Study Start Date : July 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Experimental: Dose Level 1
PM01183 + olaparib PM01183: 1 mg/m² IV olaparib 100 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin

Experimental: Dose Level 2
PM01183 + olaparib PM01183: 1 mg/m² IV olaparib 150 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin

Experimental: Dose Level 3
PM01183 + olaparib PM01183: 1.5 mg/m² IV olaparib 200 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin

Experimental: Dose Level 4
PM01183 + olaparib PM01183: 1.5 mg/m² IV olaparib 250 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin

Experimental: Dose Level 5
PM01183 + olaparib PM01183: 2 mg/m² IV olaparib 250 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin

Experimental: Dose Level 6
PM01183 + olaparib PM01183: 2 mg/m² IV olaparib 300 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin

Experimental: Dose Level 7
PM01183 + olaparib PM01183 3 mg/m² IV olaparib 300 mg BID
Drug: PM01183 + olaparib
Other Names:
  • Lynparza
  • Lurbinectedin




Primary Outcome Measures :
  1. Dose limiting toxicity [ Time Frame: 1 year ]
    To establish the Dose Limiting Toxicity in the dose escaltion study phase I

  2. Maximum tolerated dose [ Time Frame: 1 year ]
    To establish the Maximum tolerated dose in the dose escaltion study phase I

  3. Efficacy in terms of Tumor Response Rate according to RECIST 1.1 criteria. [ Time Frame: 3 years ]
    to assess the efficacy in terms of Tumor response rate according to RECIST 1.1 criteria of PM01183 in combination with olaparib in the selected populations


Secondary Outcome Measures :
  1. Pharmacodynamic evaluation to assess the increasing activity in DNA damage [ Time Frame: 1 year ]
    Pharmacodynamic evaluation to assess the increasing activity in DNA damage of the combination of PM01183+Olaparib ((double strand break).

  2. Overall response rate [ Time Frame: 3 years ]
    To evaluate the preliminary antitumor activity (overall response rate) by RECIST of the combination in the exposed population.

  3. Progression free survival. [ Time Frame: 3 years ]
    The time from inclusion until objective tumor progression or death from any cause.

  4. Biomarker analysis [ Time Frame: 3 years ]
    To explore the possible correlation between the expression of certain biomarkers and the efficacy of this therapeutic approach.

  5. To demonstrate the predictive capacity and prognostic impact of some of the biomarkers under study. [ Time Frame: 3 years ]
    • In peripheral blood:

      • Germline DNA: confirmation of HRD tumor findings if necessary.
      • PBMC: γH2AX (0 and X h after olaparib: to be defined after phase I findings) in the first cycle.
    • In archival tumor:

      • HRD panel by NGS.
      • BRCA1 methylation.
      • PTEN deficiency by IHC and/or FISH.
      • PTEN, BRCA1/2 mutation.
      • Tissue array to analyse other biomarkers by IHC (BRCA1 and other HRD genes).
    • In biopsy before study entry (limited to 15 patients):

      • IHC (RAD-51, PARP, γH2AX, PTEN, BRCA1).
      • PTEN, BRCA1/2 mutation.
      • Tissue array to analyze other immunohistochemical biomarkers (BRCA1 and other HRD genes).
    • In biopsy before study entry (limited to 15 patients):

      • IHC (RAD-51, PARP, γH2AX, PTEN, BRCA1).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients ≥18 years of age, no upper age limit.
  • Written informed consent obtained prior to any study specific procedures or assessments.
  • Histologically confirmed diagnosis of cancer:

    1. Phase I: patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
    2. Phase II: platinum-resistant ovarian cancer patients (epithelial non-mucinous), triple negative breast cancer and endometrial cancer (any grade).
  • For patients included in the phase II part of the study, evidence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 is required.

    1. 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, OR
    2. At least one lesion (measurable and/or non-measurable) that can be accurately assessed by (CT/MRI/plain x-ray) at baseline and follow up visits.
  • Patients included in the phase II part of the study must have received at least one line of standard therapy for locally advanced or metastatic disease, and developed progression disease afterwards.
  • ECOG score < 2.
  • Life expectancy of ≥ 3 months.
  • Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:

    1. Haemoglobin ≥ 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomisation (choose whichever is most applicable to the study).
    2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

    i. No features suggestive of myelodisplastic syndrome (MSD)/ Acute myeloid leukaemia (AML) on peripheral blood smear c. White blood cells (WBC) > 3x109/L d. Platelet count ≥ 100 x 109/L e. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) f. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present in which case it must be ≤ 5x ULN g. Albumin ≥ 3.0 g/dl h. Serum creatinine ≤ 1.5 x institutional ULN i. Creatinine clearance ≥ 30 ml/min.

  • Patients should sign an informed consent form before inclusion in the study that specifies that the clinical trial treatment entails consent for the analysis of biological samples of tumor and blood.
  • 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.
  • Evidence of non-childbearing status for women of childbearing potential (WOCBP)*.

WOCBP should only be included after a confirmed menstrual period and a negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1.. The inclusion of WOCBP requires use of a highly effective contraceptive measure (Appendix H).

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

  • Involvement in the planning and/or conduct of the study.
  • Previous enrolment or randomization in the present study.
  • Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment.
  • For patients included in the phase I of the study, previous treatment with olaparib or PM01183. For patients included in the phase II of the study, any previous treatment with a PARP inhibitor, including olaparib, or PM01183.
  • 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.
  • Olaparib and PM01183 are metabolized mainly by CYP3A4. Therefore, concomitant use of known strong CYP3A4 inhibitors such as ketokonazole, itraconazole, telithromycin and clarithromycin are forbidden. Concomitant use of known CYP3A4 strong inducers. (See Appendix K for a list of CYP inducers, inhibitors and substrates).
  • Persistent toxicities (≥ CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
  • Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  • 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 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 who present any contraindication or suspected allergy to the products (or any of the excipients) under investigation in the study.
  • Patients with uncontrolled seizures.
  • For patients included at the phase II part of the study: patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated insitu cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.

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): NCT02684318


Contacts
Layout table for location contacts
Contact: Andres Poveda, MD 0034961104647 apoveda@fivo.org

Locations
Layout table for location information
Spain
Hospital Reina Sofía Recruiting
Córdoba, Andalucía, Spain, 14004
Contact: Maria Jesus Rubio, MD         
Hospital Marqués de Valdecilla Recruiting
Santander, Cantabria, Spain, 39008
Contact: Ana de Juan         
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Ana Oaknin, MD    0034934894158    opadros@vhio.net   
Principal Investigator: Ana Oaknin, MD         
Hospital Ramón y Cajal Recruiting
Madrid, Spain, 28034
Contact: Eva Guerra, MD         
Hospital La Paz Recruiting
Madrid, Spain, 28046
Contact: Andrés Redondo, MD         
Fundación Instituto Valenciano de Oncología Recruiting
Valencia, Spain, 46009
Contact: Andrés Poveda, MD    0034961104647    apoveda@fivo.org   
Principal Investigator: Andrés Poveda, MD         
Sponsors and Collaborators
Poveda, Andrés, M.D.
AstraZeneca
PharmaMar
Investigators
Layout table for investigator information
Principal Investigator: Andres Poveda, MD Fundación Instituto Valenciano de Oncología
Layout table for additonal information
Responsible Party: Poveda, Andrés, M.D.
ClinicalTrials.gov Identifier: NCT02684318    
Other Study ID Numbers: POLA/ACOG1401
First Posted: February 18, 2016    Key Record Dates
Last Update Posted: June 22, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Endometrial Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Uterine Neoplasms
Uterine Diseases
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents