Solid TumorsPhase 1NCT01127178

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

A Phase 1 study testing E7016 + TMZ in people with Solid Tumors, run by Eisai Inc. at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumors
What is being tested?: E7016 + TMZ
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 5 sitesUnited States
Study dates: 29 Mar 2010to 24 Feb 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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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.

Who cannot join

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.

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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.
Any history of or concomitant medical condition or clinically significant disease making the subject medically unfit to receive the study drug or, in the opinion of the investigator, unsuitable for any other reason.
Unable to swallow multiple capsules.
History of drug or alcohol dependency or abuse within approximately the last 2 years.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Study site
Boston, Massachusetts
Study site
Charlottesville, Virginia
Study site
Greenville, South Carolina
Study site
Lebanon, New Hampshire
Study site
San Antonio, Texas

Other trials in United States

About this study

Official title: Phase 1 Study of the Poly (ADP-Ribose) Polymerase Inhibitor E7016 in Combination With Temozolomide in Subjects With Advanced Solid Tumors

Conditions: Solid Tumors
Being tested: E7016 + TMZ

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

E7016 + TMZDrug
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.

Study groups in NCT01127178
Study group	Role	What they receive
E7016 + TMZ	Experimental	Not described Receives: Drug: E7016 + TMZ

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: Cycle 1 (Cycle length = 28 days)

Secondary outcomes (3)

Objective Response Rate (ORR)
The ORR was defined as the percentage of participants with complete response (CR) plus partial response (PR) as determined by the investigator, using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in the evaluation of magnetic resonance imaging/computerized tomography (MRI/CT) scans of targeted lesions and photographs and bone scans if appropriate for the tumor type. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. ORR = CR + PR
Measured: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks
Disease Control Rate (DCR)
DCR was defined as the percentage of participants who had BOR of CR plus PR plus stable disease (SD). The best observed response (BOR) was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions. SD was defined as nonCR/non-progressive disease (PD) (NN), for participants with nontarget lesions. The minimum duration of SD was 7 weeks of multiple dose treatment. For participants who did not have target lesions, the response category NN was used instead of SD. DCR = CR + PR + SD greater than or equal to 7 weeks
Measured: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks
Overall Survival (OS)
OS was defined as the time from the first dose of E7016 until 6 Cycles of treatment or death whichever occurs first.
Measured: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Mar 201024 Feb 2011

First posted20 May 2010 (estimated)
Study start29 Mar 2010
Primary completion24 Feb 2011
Study completion24 Feb 2011

Why it stopped: Strategic decision, which is unrelated to safety

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Solid TumorsStudies of the same condition, open and under way.
More trials run by Eisai Inc.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01127178
Sponsor's protocol ID: E7016-A001-101
Status last verified: Dec 2015
First submitted: 10 May 2010
Last updated: 10 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1 Study of the Poly (ADP-Ribose) Polymerase Inhibitor E7016 in Combination With Temozolomide in Subjects With Advanced Solid Tumors
ClinicalTrials.gov ID: NCT01127178
Acronym / sponsor ID: E7016-A001-101
Conditions: Solid Tumors
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Strategic decision, which is unrelated to safety
Enrolment: 12 participants (actual)
Lead sponsor: Eisai Inc.Industry (pharma, biotech, devices)
Study start: 29 Mar 2010 (actual)
Primary completion: 24 Feb 2011 (actual)
Study completion: 24 Feb 2011 (actual)
First posted: 20 May 2010 (estimated)
Results: Posted 10 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
E7016 + TMZ	Experimental	Drug: E7016 + TMZ

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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.

Key exclusion criteria (18 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
E7016 + TMZSingle-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.	Drug	E7016 + TMZ

Primary outcome

Maximum Tolerated Dose (MTD) for E7016 in Combination With Temozolomide
Time frame: Cycle 1 (Cycle length = 28 days)
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).
Number of Participants With Dose-limiting Toxicity (DLT)
Time frame: Cycle 1 (Cycle length = 28 days)
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.
Alternative Dose of Interest (ADI) for E7016 in Combination With Temozolomide
Time frame: Cycle 1 (Cycle length = 28 days)
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.

3 secondary outcomes

Objective Response Rate (ORR)
Time frame: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks
Disease Control Rate (DCR)
Time frame: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks
Overall Survival (OS)
Time frame: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeks

Results and safety

Results posted to the registry on 10 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2	9	5
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2	3	3

Primary outcome: Maximum Tolerated Dose (MTD) for E7016 in Combination With Temozolomide

Time frame: Cycle 1 (Cycle length = 28 days). Number. Unit: mg/kg/day

Measure	Dose Escalation Part, All Participants: E7016 + Temozolomide n = 12
Value	4

Population analysed: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.

Primary outcome: Number of Participants With Dose-limiting Toxicity (DLT)

Time frame: Cycle 1 (Cycle length = 28 days). Count of participants. Unit: Participants

Measure	Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2 n = 9	Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2 n = 3
Tachycardia	0	2
Presyncope	0	2
Hypotension	0	1

Population analysed: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.

Primary outcome: Alternative Dose of Interest (ADI) for E7016 in Combination With Temozolomide

Time frame: Cycle 1 (Cycle length = 28 days)

Population analysed: An ADI was not pursued due to the limited sample size. No data was collected and analyzed to report in this outcome measure.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2	5 of 9 (55.6%)	9 of 9 (100%)	4 of 9
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Solid Tumors

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eisai Medical Services study director

Eisai Medical Services

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E7016 + TMZ in people with Solid Tumors, run by Eisai Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) for E7016 in Combination With Temozolomide (time frame: Cycle 1 (Cycle length = 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01127178.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.