PARP Inhibitor BMN-673 and Temozolomide or Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic Solid Tumors

NCT02049593 | Completed Phase 1 DMC

• 3 other identifiers: 13-001857NCI-2014-00048TRIO-US GI-07
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor BMN-673 when given together with temozolomide or irinotecan hydrochloride in treating patients with locally advanced or metastatic solid tumors. PARP inhibitor BMN-673 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help temozolomide and irinotecan hydrochloride work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PARP inhibitor BMN-673 with temozolomide or irinotecan hydrochloride may be an effective treatment for patients with advanced solid tumors.

Conditions

Metastatic Cancer; Unspecified Adult Solid Tumor

Keywords

protocol specific

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity graded using the NCI CTCAE v. 4.03

  Up to 28 days

Secondary Outcomes (10)

• Incidence of adverse events graded by NCI CTCAE v. 4.03

  Up to 12 months

• Levels of PARP inhibitory BMN 673

  Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2

• levels of temozolomide

  Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2

• Levels of irinotecan hydrochloride

  Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2

• Biomarker levels in blood and tumor tissue

  Baseline and Cycle1 Day 21 for participants undergoing biopsy (expansion phase only)

Study Arms (2)

Arm A (PARP inhibitor BMN-673, temozolomide)

EXPERIMENTAL

Patients receive PARP inhibitor BMN-673 PO QD on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: PARP inhibitor BMN-673; Drug: temozolomide; Other: pharmacological study; Other: laboratory biomarker analysis

Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride)

EXPERIMENTAL

Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: PARP inhibitor BMN-673; Drug: irinotecan hydrochloride; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

PARP inhibitor BMN-673 DRUG

Given PO

Also known as: BMN 673, BMN-673

Arm A (PARP inhibitor BMN-673, temozolomide); Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride)

temozolomide DRUG

Given PO

Also known as: SCH 52365, Temodal, Temodar, TMZ

Arm A (PARP inhibitor BMN-673, temozolomide)

irinotecan hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E

Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm A (PARP inhibitor BMN-673, temozolomide); Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (PARP inhibitor BMN-673, temozolomide); Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST, v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT may be =\< 5 x ULN
• Total serum bilirubin =\< 1.5 x ULN
• Calculated creatinine clearance of \>= 40 ml/min; as per Cockcroft-Gault formula
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 100,000/mm\^3
• Able to take oral medications
• Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 30 days after the last dose of BMN 673
• Females of childbearing potential must have a negative serum pregnancy test at screening

You may not qualify if:

• Prior treatment with a PARP inhibitor
• Prior allergic reaction or severe intolerance to either irinotecan or temozolomide
• History of central nervous system (CNS) metastasis that are untreated or not stable
• Any antitumor systemic cytotoxic therapies within 28 days prior to enrollment (6 weeks for nitrosoureas or mitomycin-C); prior high-dose chemotherapy with bone marrow or stem cell transplant is excluded
• Is known to have human immunodeficiency virus (HIV) or has active hepatitis C virus (HCV), or active hepatitis B virus (HBV)
• Has had major surgery within 28 days prior to enrollment
• Active gastrointestinal tract disease with malabsorption syndrome
• Requirement for IV alimentation
• Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina, or unstable cardiac arrhythmia requiring medication (atrial fibrillation is permitted)
• Use of any investigational product or investigational medical device within 28 days prior to enrollment
• Concurrent disease or condition that would interfere with study participation or safety, such as:
• Active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade \> 2 by NCI CTCAE (v 4.03) within 14 days prior to enrollment
• Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
• Non-healing wound, ulcer, or bone fracture

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Translational Research in Oncology: collaborator
• BioMarin Pharmaceutical: collaborator
• Medivation, Inc.: collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

talazoparib; Temozolomide; Irinotecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Zev Wainberg

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 27, 2014
• First Posted: January 30, 2014
• Study Start: June 12, 2014
• Primary Completion: October 7, 2019
• Study Completion: October 7, 2019
• Last Updated: September 26, 2022

Record last verified: 2019-11

Locations

US (1)