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

NCT02684318 | Unknown Phase 1

• 1 other identifier: POLA/ACOG1401
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Advanced Cancer; Ovarian Cancer; Endometrial Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity

  To establish the Dose Limiting Toxicity in the dose escaltion study phase I

  1 year

• Maximum tolerated dose

  To establish the Maximum tolerated dose in the dose escaltion study phase I

  1 year

• Efficacy in terms of Tumor Response Rate according to RECIST 1.1 criteria.

  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

  3 years

Secondary Outcomes (5)

• Pharmacodynamic evaluation to assess the increasing activity in DNA damage

  1 year

• Overall response rate

  3 years

• Progression free survival.

  3 years

• Biomarker analysis

  3 years

• To demonstrate the predictive capacity and prognostic impact of some of the biomarkers under study.

  3 years

Study Arms (7)

Dose Level 1

EXPERIMENTAL

PM01183 + olaparib PM01183: 1 mg/m² IV olaparib 100 mg BID

Drug: PM01183 + olaparib

Dose Level 2

EXPERIMENTAL

PM01183 + olaparib PM01183: 1 mg/m² IV olaparib 150 mg BID

Drug: PM01183 + olaparib

Dose Level 3

EXPERIMENTAL

PM01183 + olaparib PM01183: 1.5 mg/m² IV olaparib 200 mg BID

Drug: PM01183 + olaparib

Dose Level 4

EXPERIMENTAL

PM01183 + olaparib PM01183: 1.5 mg/m² IV olaparib 250 mg BID

Drug: PM01183 + olaparib

Dose Level 5

EXPERIMENTAL

PM01183 + olaparib PM01183: 2 mg/m² IV olaparib 250 mg BID

Drug: PM01183 + olaparib

Dose Level 6

EXPERIMENTAL

PM01183 + olaparib PM01183: 2 mg/m² IV olaparib 300 mg BID

Drug: PM01183 + olaparib

Dose Level 7

EXPERIMENTAL

PM01183 + olaparib PM01183 3 mg/m² IV olaparib 300 mg BID

Drug: PM01183 + olaparib

Interventions

PM01183 + olaparib DRUG

Also known as: Lynparza, Lurbinectedin

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; Dose Level 6; Dose Level 7

Eligibility Criteria

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

You may qualify if:

• 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:
• Phase I: patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
• 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.
• 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
• 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:
• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Poveda, Andrés, M.D.: lead
• AstraZeneca: collaborator
• PharmaMar: collaborator

Study Sites (6)

Hospital Reina Sofía

Córdoba, Andalusia, 14004, Spain

RECRUITING

Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital La Paz

Madrid, 28046, Spain

RECRUITING

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms; Breast Neoplasms

Interventions

PM 01183; olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Andres Poveda, MD

  Fundación Instituto Valenciano de Oncología

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andres Poveda, MD

CONTACT

0034961104647; apoveda@fivo.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 18, 2016
• Study Start: July 1, 2015
• Primary Completion: July 1, 2019
• Study Completion: October 1, 2019
• Last Updated: June 22, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)