FIGO Stage III and IV Fallopian Tube Cancer, FIGO Stage III and IV Ovarian Cancer, FIGO Stage III Primary Peritoneal Cancer
Conditions
Brief summary
This is a single center, randomized phase II study of an IL-15Rα-Fc super-agonist complex (ALT-803) given as maintenance therapy after the completion of 1st line IV/IP chemotherapy for the treatment of advanced ovarian, fallopian tube, and primary peritoneal cancer.
Detailed description
In this study all patients receive four 8 week cycles of ALT-803 consisting of 4 weekly doses followed by a 4 week rest (no treatment). As it is not known how intraperitoneal (IP) administration (a route of drug administration frequently used for gynecologic cancers) of ALT-803 compares to subcutaneous (SQ) administration, both routes of administration will be tested. The primary objective of this trial is to select one method of delivery for further testing.
Interventions
BIOLOGICALALT-803 Subcutaneous
Patient receives ALT-803 10 mcg/kg subcutaneous weekly x 4 followed by 4 weeks of no treatment before continuing with treatment courses 2, 3, and 4. Treatment courses 2, 3, and 4 are identical for all patients - ALT-803 10 mcg/kg subcutaneous weekly x 4 with a 4 week rest (4 weeks on/4 weeks off)
BIOLOGICALALT-803 Intraperitoneal
Patient receives ALT-803 10 mcg/kg intraperitoneal weekly x 4 weeks followed by 4 weeks of no treatment before continuing with treatment courses 2, 3, and 4. Treatment courses 2, 3, and 4 are identical for all patients - ALT-803 10 mcg/kg subcutaneous weekly x 4 with a 4 week rest (4 weeks on/4 weeks off).
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of FIGO stage III or grade IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma, has received at least 3 cycles of first line IV/IP cisplatin and paclitaxel chemotherapy and has stable disease or better - refer to Appendix II for FIGO staging system (Note: to be eligible for this study, the patient must receive a minimum of 3 cycles of IP therapy; however, patients may continue on IV only 1st line therapy for additional cycles as long as inclusion criteria 4.1.2 is met) * Able to begin study therapy within 3 months of final dose of first line chemotherapy * Functioning intraperitoneal catheter * ≥ 18 years of age * GOG performance status ≤ 2 (Appendix II) * Adequate organ function within 14 days of enrollment defined as: * Hematology: hemoglobin ≥ 8 g/dl, absolute neutrophil count (ANC) ≥ 1500/ul, platelets ≥ 50 x 109/L * Creatinine: ≤ 2.0 mg/dL * Hepatic: SGOT and SGPT ≤ 3 x upper limit of institutional normal (ULN) * Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to and while receiving ALT-803 * Voluntary written consent prior to the performance of any research related procedures
Exclusion criteria
* Received any investigational agent within the 14 days before the start of ALT-803 * Class II or greater New York Heart Association Functional Classification criteria (Appendix II) or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy) * Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds) * Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed * Active autoimmune disease requiring systemic immunosuppressive therapy * History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible) * Uncontrolled hypertension: defined as ≥2 readings over 160 mmHg systolic or 110 mmHg diastolic within month prior to enrollment despite optimal anti-hypertensive medication. Patients with high readings which improve to ≤160/110 after adjustment of medications will be eligible. * History of pulmonary disease or abnormal pulmonary function studies * History of narcolepsy or any neurological condition which may impair consciousness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 6 months | Incidence of Progression Free Survival after first treatment of ALT-803. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 1 year | Incidence of Progression Free Survival after first treatment of ALT-803.. Survival probability estimate. |
| Overall Survival | 1 year | Overall Survival from start of ALT-803 dosing |
| ALT-803 Associated Toxicities | 1 year | Incidence of ALT-803 associated toxicities after first treatment of ALT-803. |
| Incidence of Recorded Toxicity Grade 3 or Greater | 1 year | Grade 3 adverse events or greater will be measured. A Grade 3 adverse event is defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: ALT-803 Subcutaneous Only ALT-803 Subcutaneous: Patient receives ALT-803 10 mcg/kg subcutaneous weekly x 4 followed by 4 weeks of no treatment before continuing with treatment courses 2, 3, and 4. Treatment courses 2, 3, and 4 are identical for all patients - ALT-803 10 mcg/kg subcutaneous weekly x 4 with a 4 week rest (4 weeks on/4 weeks off) | 3 |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous ALT-803 Intraperitoneal: Patient receives ALT-803 10 mcg/kg intraperitoneal weekly x 4 weeks followed by 4 weeks of no treatment before continuing with treatment courses 2, 3, and 4. Treatment courses 2, 3, and 4 are identical for all patients - ALT-803 10 mcg/kg subcutaneous weekly x 4 with a 4 week rest (4 weeks on/4 weeks off). | 4 |
| Total | 7 |
Baseline characteristics
| Characteristic | Arm 1: ALT-803 Subcutaneous Only | Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 6 Participants |
| Region of Enrollment United States | 3 participants | 4 participants | 7 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 1 / 3 | 0 / 4 |
Outcome results
Primary
Progression Free Survival
Incidence of Progression Free Survival after first treatment of ALT-803.
Time frame: 6 months
Population: survival probability estimate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | Progression Free Survival | 50 Percentage of PFS |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Progression Free Survival | 100 Percentage of PFS |
Secondary
ALT-803 Associated Toxicities
Incidence of ALT-803 associated toxicities after first treatment of ALT-803.
Time frame: 1 year
Population: Count of events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | ALT-803 Associated Toxicities | 65 Count of events |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | ALT-803 Associated Toxicities | 100 Count of events |
Secondary
Incidence of Recorded Toxicity Grade 3 or Greater
Grade 3 adverse events or greater will be measured. A Grade 3 adverse event is defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling.
Time frame: 1 year
Population: Count of events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | Incidence of Recorded Toxicity Grade 3 or Greater | 1 Number of of adverse events |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Incidence of Recorded Toxicity Grade 3 or Greater | 2 Number of of adverse events |
Secondary
Overall Survival
Overall Survival from start of ALT-803 dosing
Time frame: 1 year
Population: survival probability estimate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | Overall Survival | 100 Percentage of participants |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Overall Survival | 100 Percentage of participants |
Secondary
Overall Survival
Overall Survival after first treatment of ALT-803.
Time frame: 2 year
Population: Survival probability estimate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | Overall Survival | 100 Percentage of participants |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Overall Survival | 100 Percentage of participants |
Secondary
Progression Free Survival
Incidence of Progression Free Survival after first treatment of ALT-803.. Survival probability estimate.
Time frame: 1 year
Population: survival probability estimate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | Progression Free Survival | 50 Percentage of participants |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Progression Free Survival | 100 Percentage of participants |
Secondary
Progression Free Survival
Incidence of Progression Free Survival after first treatment of ALT-803.. Survival probability estimate.
Time frame: 2 years
Population: survival probability estimate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: ALT-803 Subcutaneous Only | Progression Free Survival | 50 Percentage of PFS |
| Arm 2: ALT-803 Intraperitoneal and Subcutaneous | Progression Free Survival | 100 Percentage of PFS |