Recombinant Interleukin-15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in People With Refractory Cancers
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|ClinicalTrials.gov Identifier: NCT03388632|
Recruitment Status : Recruiting
First Posted : January 3, 2018
Last Update Posted : April 18, 2019
|First Submitted Date ICMJE||December 30, 2017|
|First Posted Date ICMJE||January 3, 2018|
|Last Update Posted Date||April 18, 2019|
|Actual Study Start Date ICMJE||February 5, 2018|
|Estimated Primary Completion Date||September 1, 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Safety, toxicity profile, dose-limiting toxicity (DLT), and maximumtolerated doses (MTD) [ Time Frame: Cycle 1 ]
Determine the safety, toxicity profile, DLTs, and MTD of rhIL-15 administered subcutaneously for 8 consecutive days in combination with anti-CTLA-4 and anti-PD1 monoclonal antibodies, in patients with metastatic or treatmentrefractory cancers which are not curable or do not have known measures or treatments that are associated with a survival advantage.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT03388632 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Recombinant Interleukin-15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in People With Refractory Cancers|
|Official Title ICMJE||Phase I Study of Recombinant Interleukin-15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in People With Refractory Cancers|
The drug IL-15 activates the immune system. The drugs nivolumab and ipilimumab unblock immune cells. The drugs together may allow immune cells to recognize and attack cancer cells, causing tumors to shrink.
To test the effects and maximum dose of IL-15, nivolumab, and ipilimumab.
People ages 18 and older who have cancer that does not respond to treatment
Participants will be screened with:
Tumor biopsy: A small needle removes a tumor sample.
Participants will be in 1 of 3 treatment groups:
Participants will take the drugs in four 6-week cycles. IL-15 is injected under the skin. The other two drugs are injected into an arm vein over 60-90 minutes. Participants may need to stay at the hospital 2-3 hours after the first dose of any drug to watch for side effects.
Each cycle will include:
After cycle 4, participants will stop taking IL-15. They will continue the other drugs until they can no longer tolerate the side effects or their cancer gets worse. Those cycles will include:
After participants stop treatment, their doctor will monitor their side effects for 4 months or until they go away.
- Determine the safety, toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated doses (MTD) of subcutaneous administration of rhIL-15 given in combination with the anti- CTLA-4 antibody ipilimumab and the anti-PD-1 antibody nivolumab in patients with metastatic or treatment-refractory cancers.
- Patients greater than or equal to 18 years of age with histologically confirmed solid tumor malignancy that is metastatic or treatment-refractory cancers.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms ICMJE||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||September 1, 2020|
|Estimated Primary Completion Date||September 1, 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Subjects must have histologically confirmed solid tumor malignancy that is metastatic or treatment refractory cancers which are not curable or do not have known measures or treatments that are associated with a survival advantage (as defined by the subject or the physician investigator). Enrollment of subjects with tumors that can be safely biopsied is encouraged.
Subjects must have evaluable, or measurable disease defined as greater than or equal to 1 lesion that can be accurately measured in greater than or equal to 1 dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with a spiral computed tomography (CT) scan.
Subjects must have recovered to less than or equal to grade 1 NCI Common Terminology Criteria for Adverse Events (CTCAE) or stabilized from toxicity of prior chemotherapy or biologic therapy administered more than 4 weeks or 5 half-lives earlier, whichever is shorter.
Subjects on bisphosphonates/denosumab for any cancer or on hormone therapy for prostate cancer may continue this therapy. However, subjects with prostate cancer must have confirmed metastatic disease that has progressed despite hormonal therapy or refused or is intolerant of hormonal therapy.
Age greater than or equal to 18 years.
ECOG performance status less than or equal to 2 (Karnofsky or Lansky greater than or equal to 70%.
Subjects must have normal organ and marrow function as defined below:
DLCO/VA and FEV1 greater than or equal to 50% of predicted on pulmonary function tests (subjects must have pulmonary function tests performed to be eligible)
Subjects with inactive central nervous system (CNS) metastasis are eligible. Inactive CNS metastasis is defined as: no symptoms of brain metastases after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatment.
Subjects may have previously progressed on treatment with one of the 3 agents being used in this trial or treatment with other checkpoint inhibitors, as long as they have recovered from previous toxicity. Subjects that previously progressed on treatment with a combination of any 2 of the 3 agents being used in this trial are eligible for the triplet cohort only.
The effects of ipilimumab, nivolumab, and rhIL-15 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the treatment portion of the study, and for a minimum for 5 months (women) and 7 months (men) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign a written informed consent document.
Willingness to provide blood and biopsy samples for research purposes if on the expansion phase of the study.
Subjects who have received any prior cytotoxic therapy, immunotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks or 5 halflives, whichever is shorter, prior to C1D1 (6 weeks prior for checkpoint inhibitors such as anti-CTLA-4 or anti-PD1/PD-L1 and for nitrosoureas or mitomycin C). Subjects must not have received radiotherapy in the 2 weeks prior to C1D1. Subjects who had grade greater than or equal to3 irAE during previous treatment with one of the checkpoint inhibitors are excluded from the trial; subjects who had grade 1 or 2 irAE that have resolved to grade 1 are eligible.
Subjects with primary brain cancers or active CNS metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents on this trial.
Concurrent anticancer therapy (including other investigational agents) with the exception of hormone therapy for breast or prostate cancer. Patients that have received treatment for a different cancer previously and have been disease-free for less than one year are excluded.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cognitive impairment, active substance abuse, or psychiatric illness/social situations that, in the view of the Investigator, would preclude safe treatment or the ability to give informed consent and limit compliance with study requirements.
Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding. Because there is no significant preclinical information regarding the risk to a fetus or newborn infant, pregnant or breastfeeding women will be excluded from participation in this trial.
Documented HIV infection or positive serology, active bacterial infections, serologic or PCR evidence for active or chronic hepatitis B or hepatitis C. Since rhIL-15 treatment stimulates the subjects immune system to attack their tumor, the defective immune systems of subjects with HIV or hepatitis B or hepatitis C makes responses to this treatment much less likely to provide benefit and these subjects are not eligible for this trial.
History of severe asthma or absolute requirement for chronic inhaled corticosteroid medications (subjects with a history of mild asthma that are on or can be switched to non-corticosteroid
bronchodilator regimens are eligible).
Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded.
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03388632|
|Other Study ID Numbers ICMJE||180033
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 7, 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP