The primary objective of the study is to assess the progression-free survival (PFS) of oralveliparib in combination with temozolomide (TMZ) or in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel.The…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression Free Survival [ Time Frame: Radiographic evaluation every 9 weeks,
clinical evaluation every cycle ]
Secondary outcome
•Overall Survival [ Time Frame: From Randomization until patient's death or 3
years post discontinuation ]
•Clinical Benefit Rate (CBR) [ Time Frame: From Randomization until patient's
death or 3 years post discontinuation ]
•Objective Response Rate [ Time Frame: From Randomization until patient's death
or 3 years post discontinuation ]
Background summary
Breast cancer is diagnosed in over 1.3 million women worldwide each year and
accounts for over 500,000 deaths, making it the leading cause of cancer-related
death in women. Despite recent advances in breast cancer treatment, with very
few exceptions, metastatic breast cancer remains incurable, and the aim of
treatment is to palliate symptoms and prolong the time to progression.
The therapeutic potential of PARP inhibitors was suggested by two clinical
trials evaluating PARP inhibition in breast cancer and one clinical trial in
ovarian cancer. A therapeutic potential for veliparib has also been suggested
in BRCA1/2-mutated breast cancer, and specifically for the utility of the
veliparib + TMZ combination. Therapeutic potential in breast cancer has also
been observed with veliparib in combination with carboplatin + paclitaxel. This
is the first randomized, Phase 2 study of veliparib in locally recurrent or
metastatic breast cancer in patients with deleterious germline mutation of
BRCA1 or BRCA2.
Study objective
The primary objective of the study is to assess the progression-free survival
(PFS) of oral
veliparib in combination with temozolomide (TMZ) or in combination with
carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel.
The secondary objectives of the study are to assess overall survival (OS),
clinical benefit rate (CBR), objective response rate (ORR) in those subjects
treated with veliparib in combination with TMZ or treated with veliparib plus
carboplatin and paclitaxel versus placebo plus carboplatin and paclitaxel.
Chemotherapy-Induced Peripheral Neuropathy (CIPN) will be assessed in those
subjects treated with veliparib plus carboplatin and paclitaxel versus placebo
plus carboplatin and paclitaxel. The tertiary objectives are to assess Eastern
Cooperative Oncology Group (ECOG) performance status and quality of life (QoL)
and to assess exploratory correlative endpoints.
Study design
This is a Phase 2, randomized, partially blinded, multinational, multicenter
study. Subject randomization will be stratified by estrogen receptor (ER)
and/or progesterone receptor (PgR) positive versus ER and PgR negative, prior
cytotoxic therapy versus no prior cytotoxic therapy and ECOG 0-1 versus 2.
Subjects will be randomized in a 1:1:1 ratio to one of the three treatment arms.
This study will be conducted in aproximately 120 research sites. The maximum
amount of subjects that will be enrolled are 255.
Intervention
The Screening procedures will be performed within 28 days prior to the first
dose of study drug (C1D1). For subjects randomized to the veliparib + TMZ
treatment arm, study visits will be conducted at Day 1, Day 15, and Day 22 for
the first two cycles and then Day 1 of every cycle thereafter. For subjects
randomized to the veliparib/placebo + carboplatin + paclitaxel treatment arms,
study visits will be conducted at Day 1, Day 3, and Day 17 of Cycle 1 and Day 1
and Day 3 of every cycle thereafter.
Subjects will continue dosing until they meet the defined discontinuation
criteria. When a subject meets the criteria for study discontinuation, a Final
Visit will be conducted. All subjects will have one Follow-up Visit
approximately 30 days after the last dose of veliparib + TMZ or
veliparib/placebo + carboplatin + paclitaxel.
Survival information will be collected at monthly intervals, beginning on the
date the subject is registered off study and for up to three (3) years until
the endpoint of death, until the subject has become lost to follow-up or until
study termination by AbbVie.
Study burden and risks
The burden for the subject consist of extra visits to the site, two times an
ECG, additional blood draws besides the standard safety labs. Next to this the
subject will complete at a maximum 3 questionnaires per visit. Progression of
disease will be measured every nine weeks.
The duration of the study will be different for each subject. Subjects will
continue the treatment until progression of disease criteria are met or the
subject does not tolerate the treatment.
Based on research the most frequent adverse events are for veliparib in
combination with temozolomide (>= 10%):
Feeling sick to your stomach, feeling tired, decreased platelets, constipation,
vomiting, decreased appetite, decreased neutrophils, diarrhea, headache, cough,
back pain, decreased red blood cell counts or hemoglobin, dizziness,
difficulty in breathing (shortness of breath), pain in joints, abdominal pain,
change in sense of taste, trouble with sleeping.
Based on research the most frequent adverse events are for veliparib in
combination with carboplatin and paclitaxel (>= 10%):
decreased neutrophils in the blood, feeling tired, decreased white blood cells,
feeling sick to your stomach, changes in the nerves that can cause numbness,
tingling, or pain in the hands and feet decrease in platelets, decreased
hemoglobin or hematocrit, constipation, hair loss, decreased appetite,
vomiting, muscle pains, joint pains, diarrhea, cough, shortness of breath or
difficulty breathing, difficulty sleeping, headache, swelling of the feet, pain
in the arms or legs, dizziness, abdominal pain.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
•>= 18 years of age, male and female.
•Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
•Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
•If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
•Subject has measurable disease by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria.
•Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
•Subject must have adequate bone marrow, renal and hepatic function.
•Subject must not be pregnant or plan to conceive a child.
Exclusion criteria
•Received anticancer agent(s), an investigational agent within 21 days prior, or radiotherapy within 28 days prior Cycle 1 Day 1
•More than 2 prior lines of cytotoxic chemotherapy
•Prior therapy with temozolomide, a platinum agent, or a PARP (Poly (ADP-ribose) - Polymerase) inhibitor.
•Prior taxane therapy for metastatic disease
•A history of or evidence of brain metastases or leptomeningeal disease.
•A history of uncontrolled seizure disorder
•Pre-existing neuropathy from any cause in excess of Grade 1
•Known history of allergic reaction to cremophor/paclitaxel
•Clinical significant uncontrolled conditions - active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
•Pregnant or breastfeeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-002913-12-NL |
| ClinicalTrials.gov | NCT01506609 |
| CCMO | NL43591.078.13 |