Primary Objectives:* To compare overall survival (OS) of patients who receive NKTR-102given once every 21 days (q21d) to patients who receive Treatment ofPhysician*s Choice (TPC) selected from the following list of seven singleagentintravenous…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint is Overall Survival
Secondary outcome
secondary endpoint is
objective response rate,
progression free survival,
clinical benefit rate,
Duration of Response,
Incidence and severity of treatment-emergent adverse events (TEAEs), laboratory
abnormalities, targeted symptoms (including diarrhea and neuropathy); incidence
of dose reductions; dose intensity
QLQ-C30 individual scale, overall score and BR23 score value and change over
the time of study participation
Derived PK parameters, including Cmax, AUC, time to Cmax (Tmax), V, elimination
t* and CL, with an exploratory analysis regarding possible correlation to
various baseline characteristics (eg, age and UGT1A1 status)
Selected measures of health care utilization
Quantification of CTCs and assessment of various biomarkers (eg, topoisomerase
1 and 2 expression, DNA damage and apoptosis at baseline); change from baseline
Background summary
NKTR-102 is a prodrug, that provides slow release of irinotecan, which is in
turn coverted to SN-38, a topoisomerase 1 inhibitor.The apparent elimination T*
for SN38 after NKTR-102 administration is approximately 50 days. This greatly
increased SN38 T* results in plasma SN38 concentrations that are significantly
more sustained between doses than are possible with irinotecan.
Study objective
Primary Objectives:
* To compare overall survival (OS) of patients who receive NKTR-102
given once every 21 days (q21d) to patients who receive Treatment of
Physician*s Choice (TPC) selected from the following list of seven singleagent
intravenous therapies: eribulin, ixabepilone, vinorelbine,
gemcitabine, paclitaxel, docetaxel or nab-paclitaxel
Secondary Objectives:
* To compare the objective response rate (ORR) per Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1 (hereafter referred to as
RECIST)
* To compare progression-free survival (PFS)
* To compare the clinical benefit rate (CBR, the proportion of patients
having complete response (CR), partial response (PR), or stable disease
(SD) for at least 6 months)
* To compare duration of response (DoR)
* To determine the safety profiles of NKTR-102 and TPC (including Grade
3 and higher toxicities, incidence of dose reductions and dose intensity)
* To compare health-related Quality of Life (QoL), using the QLQ-C30
questionnaire with the BR23 subscale
* To obtain pharmacokinetic (PK) data (in selected patients randomized to
NKTR-102 only)
* To evaluate the pharmacoeconomic implications of NKTR-102 therapy
using selected measures of health care utilization
Exploratory Objective
* To correlate specific biomarker data with response, PFS, survival, selected
toxicities and possibly PK parameters (in patients who consent)
Study design
This is an open-label, randomized, parallel, two arm, multicenter,
international Phase 3 study of NKTR-102 versus TPC in patients with locally
recurrent or metastatic breast cancer (MBC) previously treated with at least
two and a maximum of five prior cytotoxic chemotherapy regimens including an
anthracycline, a taxane, and capecitabine. In Arm A, NKTR-102 will be
administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute
intravenous (IV) infusion on Day 1 of each treatment cycle.
In Arm B, TPC will be administered per standard of care. TPC must be
commercially available in the medical center for treatment of patients with
cancer. Patients randomized to TPC will receive single agent chemotherapy,
limited to choice of one of the following seven agents: eribulin, ixabepilone,
vinorelbine, gemcitabine, or a taxane (paclitaxel, docetaxel or nabpaclitaxel).
TPC must consist of single-agent IV therapy (not combination therapy).
This study will randomize approximately 840 patients using a 1:1 randomization
ratio. Prior to randomization of a patient, the Investigator must determine
which TPC will be offered to the patient as part of the informed consent
process and must enter the chosen agent into the medical chart and the
central randomization system. Randomization will be stratified by geographic
region (North America/Western Europe/Australia versus Eastern Europe versus
Asia/Latin America/South Africa), prior use of eribulin (Yes versus No), and
receptor status (Triple Negative Breast Cancer [TNBC] versus HER2+ versus
Other).
Data will be collected on subsequent anticancer therapies in both treatment
arms from the time patients come off the study treatment until the time of
primary data analysis for OS.
An independent data monitoring committee (DMC) will review the safety of
NKTR-102 treatment in the study and will assess interim efficacy data.
Intervention
In Arm A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d
schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment
cycle. In Arm B, TPC will be administered per standard of care.
Study burden and risks
Common side effects Severe diarrhea & decreased number of
white blood cells dehydratation, fever, Nausea, vomiting,
fatigue,
abdominal pain, lack of appetite, blurred vision
Less common side effects Black or bloody stools, lightheadedness, dizziness,
faintness, constipation, loss of weight, loss of hair
Chest pain; shortness of
breath; or swelling in one of your limbs (signs of blood clots)
Uncommon/Rare side effects Kidney failure
leading to death Severe blood infections that may be life threatening and
thrombocytopenia (very low number of platelets)
Nektar Therapeutics, Mission Bay Boulevard South 455
San Francisco CA94158
US
Nektar Therapeutics, Mission Bay Boulevard South 455
San Francisco CA94158
US
Listed location countries
Age
Inclusion criteria
*An eligible patient is an adult female with histologically or cytologically
confirmed carcinoma of the breast. Patients may have either measurable
by RECIST v1.1 or non-measurable disease, locally recurrent or metastatic disease that is not resectable or amenable to curative treatment.
Prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic
setting) must include an anthracycline (unless not medically appropriate or
contraindicated for the patient), a taxane, and Xeloda® (capecitabine). Patients
must have received a minimum of two and a maximum of five prior cytotoxic
chemotherapy regimens for the treatment of breast cancer, with the last dose
administered within 6 months of the date of consent for this trial. Patients must
have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1 with adequate organ function. Patients with brain metastases may be eligible,
provided local therapy was completed and use of corticosteroids for this
indication discontinued for at least 3 weeks prior to randomization with stable
brain metastases (by symptoms and imaging).
The complete list of inclusion and exclusion criteria is provided in Section 5.0 .
Exclusion criteria
*Patient who have had a last dose of IV chemotherapy within 21 days, last dose of oral chemotherapy, radiotherapy within 14 days, biological therapy with 14 days or hormonal therapy within 7 days prior to randomization. Patients who have undergone high-dose chemotherapy followed by stem cell transplantation (autologous or allogeneic). Refer to Study Reference Manual for categories of anticancer therapies;*Patient with any major surgery within 28 days prior to randomization.;*Patient with concurrent use of biologic agents for the treatment of cancer including antibodies or any investigational agent(s).;*Patient with prior treatment for cancer with a camptothecin derivative.;*Patient with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care to control diarrhea in the 28 days prior to randomization.;*Patient received pharmacotherapy for hepatitis B or C, tuberculosis or HIV.;*Patient with known cirrhosis diagnosed with Child-PUGH Class A or higher liver disease.;*Patient with prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization.;*Patient requiring daily use of oxygen supplementation in the 28 days prior to randomization.;*Patients with significant cardiovascular impairment.
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 | EUCTR2011-003832-30-NL |
| ClinicalTrials.gov | NCT01492101 |
| CCMO | NL40386.072.12 |