Malignancy
Conditions
Keywords
immune checkpoint inhibitor
Brief summary
This is a phase II therapeutic interventional clinical trial that will evaluate the efficacy, safety, and outcomes of off-label immune checkpoint blockade use across malignancies.
Detailed description
Subjects will be in one of the three following groups (n=69 for each group), depending on the therapy administered: * Treatment Group A: One or more off-label immune checkpoint inhibitor (ICI) (s) alone or with other on-label ICI(s). * Treatment Group B: Off-label ICI(s) with targeted therapy. * Treatment Group C: Off-label ICI(s) with other agents that are not targeted (including, but not limited to, chemotherapy, hormonal therapy, and immunotherapy other than ICIs) with or without targeted agents. At least one ICI agent must be off-label, and no agent can be investigational; agents other than ICI can be on-label or off-label, but all have to be FDA-approved.
Interventions
DRUGOne or more off-label ICIs alone or with other on-label ICI(s)
Subjects will receive one of three ICI regimens, as prescribed by their treating medical oncologist.
DRUGOff-label ICI(s) with targeted therapy
Subjects will receive one of three ICI regimens, as prescribed by their treating medical oncologist.
DRUGoff-label ICI(s) with other agents that are not targeted (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy other than ICIs) with or without targeted agents
Subjects will receive one of three ICI regimens, as prescribed by their treating medical oncologist.
Sponsors
Medical College of Wisconsin
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Zubrod Performance Status 0-2. * Patients must have a documented malignancy where an off-label ICI is being considered by a physician. * Patients must have adequate organ function as specified below: * Absolute Neutrophil Count (ANC) ≥1,000/mcL * Platelets ≥75,000/mcL * Total Bilirubin ≤2.0 × upper limit of normal (ULN), unless the patient has changes consistent with Gilbert's Syndrome. * Alanine Aminotransferase (ALT) ≤3.0 × ULN * Serum Creatinine ≤2.0 × ULN or CrCl ≥50 mL/min as calculated by the Cockcroft-Gault equation. * 5\. Females of child-bearing potential must have a negative pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of informed consent, for the duration of study participation, and for 6 months following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception from the time of informed consent, for the duration of study participation, and 6 months after completion of administration. NOTE: A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy * Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months) * Ability to understand a written informed consent document and the willingness to sign it. * Physician has verified coverage of the cost of the drug(s) via insurance, specialty pharmacy, patient assistance programs, or other means, as documented by physician/mid-level or nursing notes, pharmacist notes, or MCW/FH insurance approval.
Exclusion criteria
* Uncontrolled illness, including symptomatic congestive heart failure (NYHA III/IV), unstable angina, or cardiac procedure within 2 weeks of start of ICI. * Concurrent therapy: use of other investigational (no FDA approval for any indication) anti-cancer agents within 14 days of registration. * Although other therapy is allowed together with the off-label ICI use as outlined in the protocol, before starting the study ICI off-label drug, the patient must be off other anti-cancer therapies for at least 2 weeks or 5 half-lives, whichever is shorter. * Major surgery (as defined by the treating medical oncologist) within two weeks of the start date of immunotherapy. * Other: pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response. | at least 6 months | The proportion of subjects who achieve complete response, partial response, or stable disease of at least 6 months, as evaluated by a physician investigator, who can use RECIST v1.1 and iRECIST. For non-solid malignancies, the standard evaluation criteria for that malignancy will be used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious adverse events | Up to 5 Years | The number of Grade ≥3 serious adverse events at least possibly related to ICIs during treatment, per NCI CTCAE v6.0. |
| Progression-Free Survival | Up to 5 years | Time from the start of off-label ICI treatment to the earliest date of documented progression, symptomatic deterioration, start of new anti-cancer therapy, or death from any cause. Progression is assessed by the treating medical oncologist. Patients alive without reported progression (including no evaluation) are censored at last contact. |
| Overall Survival | Up to 5 years | Time from the start of off-label ICI treatment to the date of death from any cause. Patients last known to be alive are censored at the date of last contact. |
Countries
United States
Contacts
CONTACTMedical College of Wisconsin Cancer Center Clinical Trials Office
PRINCIPAL_INVESTIGATORRazelle Kurzrock, MD
Medical College of Wisconsin
Outcome results
None listed