Study of Poly (ADP-Ribose) Polymerase (PARP) Inhibitor E7016 in Combination With Temozolomide in Subjects With Advanced Solid Tumors

NCT01127178 | Terminated Phase 1 Results

• 1 other identifier: E7016-A001-101
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) of poly (ADP-Ribose) polymerase inhibitor E7016 when used with temozolomide (TMZ) in patients with advanced solid tumors and gliomas.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) for E7016 in Combination With Temozolomide

  The MTD was defined as the highest dose of E7016 in combination with temozolomide at which no more than one of six participants experienced a dose-limiting toxicity (DLT). DLTs were defined as those adverse events (AEs) considered related to E7016 which occurred during the first cycle of study drug administration. DLTs were evaluated and graded based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version \[v\] 4.0).

  Cycle 1 (Cycle length = 28 days)

• Number of Participants With Dose-limiting Toxicity (DLT)

  A DLT was defined as those AEs considered related to E7016 which occurred during the first cycle of study drug administration. DLTs were evaluated and graded based on the NCI CTCAE version 4.0. The following toxicities were regarded as DLTs: a Grade 4 hematologic toxicity (lasting \[greater than or equal to\] \>=5 days); a temozolomide dose reduction for Grade \>=3 neutropenia or thrombocytopenia; or a Grade \>=3 nonhematologic toxicity (except optimally managed nausea, vomiting, or diarrhea) that was assessed by the investigator as related to study drug. A participant with two or more DLTs with the same preferred term was counted only once for that preferred term.

  Cycle 1 (Cycle length = 28 days)

• Alternative Dose of Interest (ADI) for E7016 in Combination With Temozolomide

  The ADI determination plan was based primarily on clinical, and/or PK measurements of drug concentration and/or bioactivity as defined by preclinical studies. However, the ADI was not pursued due to the limited sample size.

  Cycle 1 (Cycle length = 28 days)

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks

• Disease Control Rate (DCR)

  From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks

• Overall Survival (OS)

  From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks

Study Arms (1)

E7016 + TMZ

EXPERIMENTAL

Drug: E7016 + TMZ

Interventions

E7016 + TMZ DRUG

Single-Dose PK Period (single oral dose of E7016 on Day -7) in the Dose-Escalation Component; Multiple-Dose Treatment Cycles (7 days of oral E7016 + 5 days of oral TMZ) added in Cycle 1 of the Dose-Escalation Component and in Cycles 1 through 6 of the Expansion Component.

E7016 + TMZ

Eligibility Criteria

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

You may qualify if:

• Subjects who meet all of the following criteria may be included in the study.
• Histopathologically confirmed melanoma or other solid tumors (excluding malignant brain tumors) for which no standard therapy is available (Dose-Escalation Component only). During the Expansion Component, enrollment will be restricted to subjects with histopathologically proven gliomas and will include subjects eligible for TMZ therapy as well as those who have failed TMZ therapy; and those who are either not appropriate candidates for radiation therapy or who refuse radiation therapy. Subjects who are taking either strong cytochrome P450 (CYP) inhibitors or inducers may be enrolled.
• Life expectancy greater than or equal to 3 months after starting E7016.
• Performance status (PS) 1 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Adequate renal function indicated by serum creatinine less than 1.5 mg/dL or calculated creatinine clearance greater than 50 mL/minute.
• Adequate bone marrow reserve:
• ANC greater than or equal to 1500/mm3,
• Platelets greater than or equal to 100,000/mm3 (without transfusion),
• Hemoglobin greater than or equal to 10 g/dL (less than 10.0 g/dL is acceptable if corrected by growth factor or transfusion).
• Adequate liver function:
• Bilirubin less than or equal to 1.5x the upper limit of normal (ULN) (less than or equal to 3 x ULN if subject has liver metastases),
• Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN (less than or equal to 5 x ULN if subject has liver metastases).
• Males and females age greater than or equal to 18 years at the time of informed consent.
• Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin (BhCG) test at Visit 1 (Screening) and a negative urine pregnancy test prior to the first dose of E7016 capsules in the Single-Dose PK Period and again prior to the first dose of E7016 in Cycle 1.
• Male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, IUD) beginning at least 1 menstrual cycle prior to starting study drug(s), throughout the entire study period, and for 30 days after the last dose of study drug.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participation in the study:
• Subjects with primary or metastatic brain tumors are excluded from the Dose-Escalation Component.
• Subjects with active malignancies other than gliomas are excluded from the Expansion Component.
• Subjects taking medications which are either strong CYP inhibitors or inducers will be excluded from the Dose-Escalation Component.
• Prior treatment with a PARP inhibitor.
• Inability to tolerate 150 mg/m2/d TMZ during previous therapy with TMZ.
• Known allergy, hypersensitivity, or other contraindication to E7016, TMZ, or dacarbazine or any of the other components of the formulations.
• Known human immunodeficiency virus infection, active hepatitis B or C.
• Active infections requiring specific anti-infective therapy
• Subjects who have had a major surgical procedure (including tumor resection) within 4 weeks prior to initiating E7016 treatment.
• Subjects scheduled for surgery during the projected course of the study.
• Females who are pregnant (positive B-hCG test) or breastfeeding.
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to initiating E7016 treatment (6 weeks for mitomycin C or nitrosoureas).
• Prolongation of QTc interval (500 msec).
• Achlorhydria or use of antacids, proton-pump inhibitors, or other drugs known to raise gastric pH within 2 weeks prior to study drug administration.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (5)

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Lebanon, New Hampshire, United States

Location

Unknown Facility

Greenville, South Carolina, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Charlottesville, Virginia, United States

Location

MeSH Terms

Interventions

10-((4-hydroxypiperidin-1-yl)methyl)chromeno(4,3,2-de)phthalazin-3(2H)-one; Temozolomide

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The study was terminated due to sponsor's strategic decision, which is unrelated to safety, therefore no participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Study Officials

• Eisai Medical Services

  Eisai Medical Services

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2010
• First Posted: May 20, 2010
• Study Start: March 29, 2010
• Primary Completion: February 24, 2011
• Study Completion: February 24, 2011
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2015-12

Locations

US (5)