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This is an open-label Phase I/II study, with a dose escalation part (Phase I) and a single-arm part (Phase II), in patients with recurrent SCLC who progressed after first-line platinum-based chemotherapy and who are candidates for second line therapy. No PK evaluation is planned in this study as nivolumab and ipilimumab are unlikely to alter plinabulin's PK, since the route of excretion is different.
Full description
This is an open-label Phase I/II study, with a dose escalation part (Phase I) and a single arm part (Phase II), in patients with recurrent SCLC.
In the Phase I part, patients will receive plinabulin at escalating doses in combination with nivolumab and ipilimumab. Doses of study drug will be administered as intravenous (IV) infusions in 21 day cycles. Patients will receive all study drugs on Day 1 of each cycle. After 4 treatment cycles, ipilimumab is stopped and patients continue treatment with nivolumab and plinabulin every 2 weeks (maintenance period) or until disease progression, development of unacceptable toxicity or one of the protocol-defined reasons for treatment discontinuation occurs.
At least 3 patients will be enrolled in each cohort, starting at 20 mg/m2 of plinabulin. The dose of plinabulin will be escalated in sequential patient cohorts after the safety data from the first cycle is reviewed. Thereafter the dose of plinabulin will be escalated to 30 mg/m2, provided that dose-limiting toxicities (DLTs) are not observed per the specified criteria, until the RP2D is determined.
In the Phase II part, up to 26 patients will be treated with the triple combination of plinabulin (at RP2D) + nivolumab + ipilimumab. Patients will continue treatment until disease progression, development of unacceptable toxicity or one of the protocol-defined reasons for treatment discontinuation occurs.
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Inclusion and exclusion criteria
Inclusion Criteria:
The patients must satisfy all of the following inclusion/exclusion criteria in order to be eligible for the study:
Must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines.
Males and females aged >18 years at time of consent.
Histological or cytological confirmed extensive-stage SCLC
Patients who progressed after at least 1 platinum-based chemotherapy regimen. Patients with platinum resistance (defined as recurrence or progression of disease within 90 days of completion of the platinum-based regimen) are eligible. For phase II, patients also must have been treated with at least one prior line of PD-1/PD-L1 therapy.
Measurable disease according to RECIST v1.1 (Section 8) obtained by imaging within 28 days prior to study registration.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before registration and minimum life expectancy of at least 12 weeks.
Treatment to be initiated at least 2 weeks since last dose of prior systemic anticancer therapy (chemotherapy, radiation, and/or surgery.
Recovery to grade 1 of any clinically significant toxicity (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy) prior to initiation of study drugs.
Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti estrogens, or ovarian suppression.
Adequate laboratory values.
Exclusion Criteria
Patients with any of the following will be excluded from participation in the study.
Primary purpose
Allocation
Interventional model
Masking
39 participants in 2 patient groups
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Central trial contact
Ahran Lee; Salma Jabbour, MD
Data sourced from clinicaltrials.gov
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