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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01286987
First received: January 26, 2011
Last updated: October 7, 2014
Last verified: October 2014
  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:


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: December 2014 (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
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, see Learn About Clinical Studies.

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

Locations
United States, Arizona
TGen Clinical Research Services
Scottsdale, Arizona, United States, 95258
United States, California
University of California Los Angeles (UCLA)
Santa Monica, California, United States, 90404
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United Kingdom
Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Gilles Gallant 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: October 7, 2014
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
Lung Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Pancreatic Neoplasms
Prostatic Neoplasms
Sarcoma, Ewing
Small Cell Lung Carcinoma
Adnexal Diseases
Breast Diseases
Bronchial Neoplasms
Carcinoma, Bronchogenic
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Diseases, Male
Genital Neoplasms, Female
Genital Neoplasms, Male
Gonadal Disorders
Lung Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Bone Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Osteosarcoma
Ovarian Diseases

ClinicalTrials.gov processed this record on October 20, 2014