Study of BMN 673, a PARP Inhibitor, in Patients With Advanced or Recurrent Solid Tumors - Full Text View

Purpose

This is a single-arm, open-label study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BMN 673 in patients with advanced tumors with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation phase in which the maximum tolerated dose will be defined, and a dose expansion phase.

Condition	Intervention	Phase
Advanced or Recurrent Solid Tumors Breast Neoplasms Ovarian Cancer, Epithelial Ewing Sarcoma Small Cell Lung Carcinoma Prostate Cancer Pancreas Cancer	Drug: BMN 673	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1, First in Human, Single-arm, Open-label Study of Once a Day, Orally Administered BMN 673 in Patients With Advanced or Recurrent Solid Tumors

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer Ewing sarcoma

MedlinePlus related topics: Breast Cancer Cancer Lung Cancer Ovarian Cancer Pancreatic Cancer Prostate Cancer Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:

The primary outcome of this study is to determine the maximum tolerated dose (MTD) of daily oral BMN 673 [ Time Frame: Assessed after each visit until completion of Part 1 (Estimated duration is 12-18 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Number of participants with adverse events [ Time Frame: Assessed after each visit until completion of the study (Estimated duration is 24-30 months) ] [ Designated as safety issue: Yes ]
Determine the pharmacokinetic (PK) profile of BMN 673 [ Time Frame: Assessed at each visit in cycle 1 - 5 (Estimated duration is 24 months) ] [ Designated as safety issue: No ]
Sample collection times vary per visit. PK parameters that will be evaluated include: maximum concentration (Cmax), minimum concentration (Cmin), time to maximum plasma concentration (Tmax), area under the curve from 0 to last quantifiable sampling point post-dose (AUC0-inf), are under the curve extrapolated to infinity (AUC0-last), half life (t1/2), systemic clearance (CL/f) and volume of distribution (VZ/f)
Determine the Recommended Phase 2 Dose (RP2D) of oral daily BMN 673 [ Time Frame: Assessed after each visit until completion of the study (Estimated duration is 24-30 months) ] [ Designated as safety issue: No ]
Assess preliminary efficacy of BMN 673 by Response Rate, based on RECIST (Response Evaluation Criteria In Solid Tumors) [ Time Frame: Assessed approximately every 8 weeks (Estimated duration is 24-30 months) ] [ Designated as safety issue: No ]

Estimated Enrollment:	85
Study Start Date:	December 2010
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BMN 673	Drug: BMN 673 Oral capsule with multiple dosage forms given once daily

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor
Must have available archived tumor tissue (formalin-fixed paraffin-embedded) [FFPE].
18 years of age or older.
Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9 (pancreatic cancer).
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Have adequate organ function
Able to take oral medications.
Willing and able to provide informed consent.
Sexually active patients must be willing to use an acceptable method of contraception.
Females of childbearing potential must have a negative serum pregnancy test at screening.
Willing and able to comply with all study procedures.

Part 2 Dose Expansion Tumor Types:

Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 4 prior regimens for metastatic disease.
Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 2 prior regimens for metastatic disease.
Small cell lung cancer (SCLC) patients who have received no more than one prior regimen for SCLC.
Ewing's sarcoma patients who have received no more than 3 prior regimens for metastatic disease.

Exclusion Criteria:

Part 2 Expansion: Prior treatment with a PARP inhibitor.
Has history of central nervous system (CNS) metastasis.

* Exception: In patients with SCLC, history of adequately treated brain metastasis who do not require corticosteroids for management of CNS symptoms.
Has had major surgery within 28 days before Cycle 1, Day 1.
Has active peptic ulcer disease.
Active gastrointestinal tract disease with malabsorption syndrome.
Pregnant or breastfeeding at screening or planning to become pregnant (in each case, either oneself or one's partner) at any time during the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286987

Contacts

Contact: Elva Mazabel

415-506-6662

emazabel@bmrn.com

Locations

United States, Arizona
TGen Clinical Research Services	Recruiting
Scottsdale, Arizona, United States, 95258
Contact: Joyce Schaffer, MSN RN OCN 480-323-1339 joschaffer@shc.org
Principal Investigator: Ramesh Ramanathan, MD
United States, California
University of California Los Angeles (UCLA)	Recruiting
Santa Monica, California, United States, 90404
Contact: Lisa M Yonemoto 310-582-4069 lyonemoto@mednet.ucla.edu
Principal Investigator: Zev Wainberg, MD
United States, Indiana
Indiana University Simon Cancer Center	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kisha Horan 317-274-4262 knhoran@iupui.edu
Principal Investigator: Lida Mina, MD
United States, Michigan
University of Michigan Health System	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Nabeela Iqbal 734-232-0759 nabeela@umich.edu
Principal Investigator: Rashmi Chugh, MD
United States, Texas
University of Texas MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Anne Meschwitz 713-745-6773 ameschwi@mdanderson.org
Principal Investigator: Lauren A Byers, MD
United Kingdom
Royal Marsden Hospital	Recruiting
Sutton, United Kingdom, SM2 5PT
Contact: Sonia Serrano +44 (0) 20 8722 4087 Sonia.Serrano@icr.ac.uk
Principal Investigator: Johann de Bono, MD

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

Study Director:

Andrew Dorr, MD

BioMarin Pharmaceutical

More Information

No publications provided

Responsible Party:	BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:	NCT01286987 History of Changes
Other Study ID Numbers:	PRP-001
Study First Received:	January 26, 2011
Last Updated:	January 24, 2013
Health Authority:	United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by BioMarin Pharmaceutical:

BRCA1 Protein
BRCA2 Protein

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms
Carcinoma
Lung Neoplasms
Ovarian Neoplasms
Pancreatic Neoplasms
Prostatic Neoplasms
Small Cell Lung Carcinoma
Sarcoma, Ewing's
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial
Sarcoma
Neoplasms by Site
Breast Diseases
Skin Diseases

Neoplasms by Histologic Type
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Digestive System Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on May 19, 2013