Phase 2 Study of the Poly(ADP-Ribose) Polymerase Inhibitor E7016 in Combination With Temozolomide in Subjects With Wild Type BRAF Stage IV or Unresectable Stage III Melanoma

NCT01605162 | Terminated Phase 2

• 1 other identifier: E7016-A001-201
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, open-label, multicenter study to assess the PFS-6m of E7016 at the selected dose of 320-mg once daily (QD) in combination with 150-mg/m2 of Temozolomide (TMZ) in subjects with wt BRAF Stage IV or unresectable Stage III melanoma with disease progression. Eligible subjects must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST).

Conditions

Wild Type BRAF Stage IV Melanoma; Unresectable Stage III Melanoma

Outcome Measures

Primary Outcomes (1)

• The Progression Free Survival-6m rate defined as the proportion of subjects that are alive and progression-free at 6-months from the date of first dosing based on RECIST 1.1.

  The Progression Free Survival-6m rate defined as the proportion of subjects that are alive and progression-free at 6-months from the date of first dosing based on RECIST 1.1. PFS-6m rate will be estimated from Kaplan-Meier (K-M) product-limit estimate of PFS.

  6 months

Study Arms (1)

E7016 plus TMZ

EXPERIMENTAL

Drug: TMZ; Drug: E7016

Interventions

TMZ DRUG

TMZ (at 150 mg/m2) will be administered orally according to the instructions on the product label, on Days 1 through 5 of the same 28-day cycle as E7016. TMZ capsules should be taken immediately after E7016. No food or drink intake, except water, will be allowed for 2 hours before or after administration.

E7016 plus TMZ

E7016 DRUG

E7016 capsules will be administered in the morning after at least a 2-hour fast. Subjects will be instructed not to eat or drink anything except water in the 2 hours prior and 2 hours after drug administration. Subjects will record the time at which they ate. For the Single-Dose PK Period, 320 mg of E7016 will be administered once on Day -2. For the Multiple-Dose Treatment Cycle(s), 320 mg E7016 will be administered QD on Days 1 through 7 of each 28-day cycle.

E7016 plus TMZ

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all the following criteria to be included in this study:
• Males and females greater than or equal to 18 years of age
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
• Life expectancy greater than or equal to 3 months after starting E7016
• Performance status of 0 - 2 on the Eastern Cooperative Oncology Group (ECOG) scale
• Histopathologically confirmed diagnosis of melanoma with wt BRAF status (except melanoma of intraocular origin) with disease progression
• American Joint Committee on Cancer (AJCC) Stage IV melanoma or unresectable Stage III melanoma
• Measurable disease meeting the following criteria:
• At least one lesion of greater than or equal to 1.0 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only one target lesion and it is a non-lymph node, it should have a longest diameter of greater than or equal to 1.5 cm.
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
• Subjects with brain metastases will be eligible under the following conditions:
• have undergone complete surgical excision and are more than 1 month post-surgery with no radiographic evidence of disease recurrence in the brain or
• have undergone stereotactic radio surgery (gamma knife procedure or radiotherapy ) and are more than 1 month post procedure and with no radiographic evidence of disease progression in the brain and
• are asymptomatic and
• discontinued corticosteroid treatment and/or anticonvulsive therapy at least 1 week prior to Cycle 1, Day 1

You may not qualify if:

• Subjects with any one of the following will be excluded from this study:
• Subjects with melanoma of intraocular origin
• Subjects taking medications which are either strong CYP inhibitors or inducers
• Subjects with active malignancies except for wt BRAF Stage IV and unresectable Stage III melanoma, basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, adequately treated Stage I or II cancer from which the subject is currently in complete remission, or any other cancer from which the subject has been disease-free for 5 years
• Prior treatment with a PARP inhibitor
• Prior treatment with dacarbazine (DTIC) or TMZ containing regimens
• Subjects with known allergy, hypersensitivity, or other contraindication to E7016, TMZ, or DTIC or any of the other components of the formulations
• Subjects with known human immunodeficiency virus infection (HIV), active hepatitis B or C
• Subjects with 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
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to initiating E7016 treatment (6 weeks for mitomycin C or nitrosoureas) or any investigational agent within 30 days prior to the first dose of study drug or who have not recovered (Grade 0 or 1) from any acute toxicity related to previous anticancer treatment
• Prolongation of QT corrected, the QT interval corrected for heart rate (QTc) interval (greater than 480 ms)
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II ; unstable angina; uncontrolled hypertension despite optimal treatment, myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment
• Subjects with malabsorption syndrome or any other condition that might affect bioavailability of study drug (E7016 or TMZ)

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Unknown Facility

Pittsburgh, Pennsylvania, United States

Location

MeSH Terms

Interventions

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

Study Officials

• Eisai Medical Services

  Eisai Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2012
• First Posted: May 24, 2012
• Study Start: May 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: July 28, 2016

Record last verified: 2016-07

Locations

US (1)