Etirinotecan Pegol (NKTR-102) in NSCLC
Study Details
Study Description
Brief Summary
This Phase 2 study is designed to characterize the objective response rate (defined as complete response (CR) and partial response (PR)) of Etirinotecan pegol administered to subjects with metastatic and recurrent NSCLC after failure of 2nd line therapy. Up to 37 eligible subjects will receive the investigational drug q3 weeks until they are no longer benefiting.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a Phase 2 study designed to characterize the objective response rate (defined as complete response (CR) and partial response (PR)) of Etirinotecan pegol (NKTR-102) administered to subjects with metastatic and recurrent NSCLC after failure of 2nd line therapy. Up to 37 eligible subjects will be enrolled at the University of Pennsylvania.
One cycle will be defined as 3 weeks. Patients will be followed clinically every week for the first cycle with laboratory parameters and physical exam. Response will be determined by RECIST version1.1 after 2 cycles of therapy. Patients with stable disease (SD), PR or CR will continue on treatment for up to six cycles. Those who are benefitting after six cycles will have the option of continuing on treatment. Patients with progressive disease will be taken off study and will be followed for OS data.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Eligible patients will receive etirinotecan pegol at a dose of single-arm, open-label study is designed to investigate the efficacy and safety of etirinotecan pegol in patients with metastatic or recurrent NSCLC after failure of 2nd line therapy. Eligible patients will receive etirinotecan pegol at a dose of 145 mg/m2 iv every 3 weeks. One cycle will be defined as 3 weeks. Patients will be followed clinically every week for the first cycle with laboratory parameters (section 6.2.1) and physical exam. Response will be determined with RECIST version 1.1 after 2 cycles of therapy. Patients with Stable disease (SD), partial response (PR) or complete response (CR) will continue on additional therapy for up to six cycles. In the absence of disease progression in subjects completing six full cycles, further treatment beyond cycle #6 will be left to the discretion of the treating physician and his/her staff. Patients with progressive disease will be taken off study and will be followed for OS |
Drug: Etirinotecan pegol (NKTR-102)
Eligible patients will receive etirinotecan pegol at a dose of 145 mg/m2 iv every 3 weeks. One cycle will be defined as 3 weeks. Treatment will be administered on an outpatient basis.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Objective Response Rate [6 weeks]
The primary objective of this phase 2 trial is to estimate the objective response rate (Complete Response or Partial Response, as measured by RECIST version 1.1) for patients with metastatic or recurrent NSCLC being treated with etirinotecan pegol after failure of second-line therapy.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically confirmed metastatic or recurrent NSCLC. Primary or metastatic site may be used for histology.
-
After failure of 2nd line treatment with up to two prior lines of therapy, one of which may be an oral TKI.
-
Measurable disease (Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented incontrovertibly either radiographically or pathologically. For clinicians relying on biopsy documentation of recurrence, this must be obtained to confirm persistence at least 90 days following completion of radiation therapy).
-
Eastern Cooperative Oncology Group (ECOG) performance status is 0-1.
-
Age at the time of study entry is ≥ 18 years.
-
Adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9.0 g/dL, and a platelet count ≥ 100,000/μL obtained within 2 weeks prior to enrollment.
-
Adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × the upper limit of normal ([ULN]), or ≤ 5 × the ULN in the presence of known liver metastases.
-
Alkaline phosphatase (AP) ≤ 3 x the ULN or ≤ 5 × the ULN in the presence of known liver metastases
-
Adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the patient's measured or calculated creatinine clearance (CrCl) must be ≥ 50 mL/min.
-
Resolution of chemotherapy and radiation therapy related toxicities to NCI-CTCAE version 4.0 Grade 1 or lower severity, except for diarrhea (which must be Grade 0 without a supportive antidiarrheal medications) and alopecia (any grade).
-
Women of childbearing potential and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to enrollment and for the duration of study participation. Protections against pregnancy must be continued for at least 8 months after the last dose of study drug.
-
Signed informed consent.
Exclusion Criteria:
-
Untreated central nervous system metastases. Patients are eligible if they are clinically stable, off all steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to enrollment, or after surgical resection performed at least 2 weeks prior to enrollment.
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History of another "active" invasive primary cancer requiring ongoing treatment.
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Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent.
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Patients who have had chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C), radiotherapy within 14 days, biological therapy within 14 days, hormonal therapy within 7 days, and investigational therapy within 21 days prior to enrollment.
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Patients who have had any major surgery within 21 days prior to enrollment.
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Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
-
Patients with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care (more than 3 days/week) to control diarrhea in the 28 days prior to enrolment.
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Administration of the CYP3A4 inducers or inhibitors, as they may induce or inhibit irinotecan or SN38 metabolism within 14 days prior to cycle 1 and throughout study treatment. For a list of these agents, see: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti onsLabeling/ucm093664.htm
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Uncontrolled thrombotic or hemorrhagic disorder.
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Known human immunodeficiency virus (HIV) positivity.
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The patient, if female, is pregnant or lactating.
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Previous therapy with a topoisomerase I or II inhibitor.
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Known allergy to any of the treatment components.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- Abramson Cancer Center of the University of Pennsylvania
Investigators
- Principal Investigator: Charu Aggarwal, MD, Abramson Cancer Center of the University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UPCC 18512
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Etirinotecan Pegol |
|---|---|
| Arm/Group Description | 145 mg/m2 will be administered as an IV infusion over a course of 90 minutes on Day 1 of a 21 day cycle |
| Period Title: Overall Study | |
| STARTED | 40 |
| COMPLETED | 37 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Etirinotecan Pegol |
|---|---|
| Arm/Group Description | This Phase II, single-arm, open-label study is designed to investigate the efficacy and safety of etirinotecan pegol in patients with metastatic or recurrent NSCLC after failure of 2nd line therapy. Eligible patients will receive etirinotecan pegol at a dose of 145 mg/m2 iv every 3 weeks. One cycle will be defined as 3 weeks. Patients will be followed clinically every week for the first cycle with laboratory parameters and physical exam. Response will be determined with RECIST version 1.1 after 2 cycles of therapy. Patients with Stable disease (SD), partial response (PR) or complete response (CR) will continue on additional therapy for up to six cycles. In the absence of disease progression in subjects completing six full cycles, further treatment beyond cycle #6 will be left to the discretion of the treating physician and his/her staff. Patients with progressive disease will be taken off study and will be followed for overall survival. |
| Overall Participants | 40 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
14
35%
|
| >=65 years |
26
65%
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
66
|
| Sex: Female, Male (Count of Participants) | |
| Female |
18
45%
|
| Male |
22
55%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
5
12.5%
|
| Not Hispanic or Latino |
33
82.5%
|
| Unknown or Not Reported |
2
5%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
7.5%
|
| White |
34
85%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
3
7.5%
|
Outcome Measures
| Title | Overall Objective Response Rate |
|---|---|
| Description | The primary objective of this phase 2 trial is to estimate the objective response rate (Complete Response or Partial Response, as measured by RECIST version 1.1) for patients with metastatic or recurrent NSCLC being treated with etirinotecan pegol after failure of second-line therapy. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Etirinotecan Pegol |
|---|---|
| Arm/Group Description | This Phase II, single-arm, open-label study is designed to investigate the efficacy and safety of etirinotecan pegol in patients with metastatic or recurrent NSCLC after failure of 2nd line therapy. Eligible patients will receive etirinotecan pegol at a dose of 145 mg/m2 iv every 3 weeks. One cycle will be defined as 3 weeks. Patients will be followed clinically every week for the first cycle with laboratory parameters and physical exam. Response will be determined with RECIST version 1.1 after 2 cycles of therapy. Patients with Stable disease (SD), partial response (PR) or complete response (CR) will continue on additional therapy for up to six cycles. In the absence of disease progression in subjects completing six full cycles, further treatment beyond cycle #6 will be left to the discretion of the treating physician and his/her staff. Patients with progressive disease will be taken off study and will be followed for overall survival. |
| Measure Participants | 37 |
| Partial Response |
2
5%
|
| Stable Disease |
17
42.5%
|
| Progressive Disease |
18
45%
|
Adverse Events
| Time Frame | 7 months | |
|---|---|---|
| Adverse Event Reporting Description | As per CTCAE | |
| Arm/Group Title | Etirinotecan Pegol | |
| Arm/Group Description | Etirinotecan pegol (NKTR-102): 145mg/m2 intravenously every 3 weeks | |
All Cause Mortality |
||
| Etirinotecan Pegol | ||
| Affected / at Risk (%) | # Events | |
| Total | 37/40 (92.5%) | |
Serious Adverse Events |
||
| Etirinotecan Pegol | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/40 (12.5%) | |
| Blood and lymphatic system disorders | ||
| Sepsis | 1/40 (2.5%) | 1 |
| Thromboembolic Event | 1/40 (2.5%) | 1 |
| Nervous system disorders | ||
| Treatment-related seconard maligancy | 1/40 (2.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Respiratory Failure | 1/40 (2.5%) | 1 |
| Pleural Effusion | 1/40 (2.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Etirinotecan Pegol | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Charu Aggarwal |
|---|---|
| Organization | University of Pennsylvania (Abramson Cancer Center) |
| Phone | 2156624000 |
| charu.aggarwal@pennmedicine.upenn.edu |
- UPCC 18512