Copanlisib and Gemcitabine in Relapsed/Refractory PTCL
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|ClinicalTrials.gov Identifier: NCT03052933|
Recruitment Status : Recruiting
First Posted : February 14, 2017
Last Update Posted : April 11, 2018
COPGEM (Copanlisib and Gemcitabine)chemotherapy regimen is proposed as the salvage treatment for relapsed or refractory peripheral T-cell or NK/T-cell lymphomas in this study protocol, which would be expected to be feasible and effective in this group of patients.
Copanlisib (BAY 80-6946), a highly selective and potent class-1 PI3K inhibitor with sub-nanomolar IC50s against PI3Kα and PI3Kδ, has demonstrated activity in relapsed/refractory, aggressive NHLs, suggesting an ORR of 50% for T-cell lymphomas.
Gemcitabine has demonstrated clinical antitumor activity against PTCLs including NK/T-cell lymphomas both as single-agent (ORR 30-50%) and in combination therapy, with limited extramedullary toxicities.
Considering the evidence of activity for both agents against PTCLs, the investigators propose that targeted therapy with copanlisib in combination with gemcitabine will exhibit early elimination of rapidly growing tumor cells and be a rational therapeutic modality for use in relapsed or refractory PTCLs, if the overlapping toxicities can be managed.
|Condition or disease||Intervention/treatment||Phase|
|Mature T-Cell and NK-Cell Neoplasm||Drug: Copanlisib Drug: Gemcitabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Prospective, Multicenter, Open-labeled, Phase I/II Study of the Efficacy and Safety of Copanlisib (BAY 80-6946) and Gemcitabine Combination in Patients With Relapsed/Refractory Peripheral T-cell or NK/T-cell Lymphoma|
|Actual Study Start Date :||February 1, 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
For phase I study, participants will receive copanlisib (in combination with gemcitabine) IV infusion at a dose of 45 mg or 60 mg on Days 1, 8, and 15 of each 28-day treatment cycle. During phase I study, participants will be treated at the level of 45 mg/dose (level1), or 60 mg/dose (level II) of copanlisib. Maximal tolerated dose will be determined by standard 3+3 dose escalation design For phase II study, copanlisib dose level, determined during phase I study, will be administered on Days 1, 8, and 15.
Maximum 6 cycles of gemcitabine and copanlisib combination and subsequent copanlisib monotherapy in participants with ≥ SD to copanlisib and gemcitabine until maximum 12 cycles will be given for this study.
For phase I/II study, participants will receive gemcitabine (in combination with copanlisib) IV infusion at fixed dose of 1,200 mg/m2 on Days 1 and 15 of each 28-day treatment cycle until maximum 6 cycles.
- Dose limiting toxicity (DLT), Maximum tolerated dose (MTD) for phase I [ Time Frame: 4 weeks ]The recommended dose of the combination of copanlisib and gemcitabine in patients with mature T-cell or NK/T cell neoplasm
- Objective response rate for phase II [ Time Frame: 1 year ]Primary efficacy data will be maximal change of radiological tumor lesion measurement using CT scan at baseline and every two cycles, with the evaluation of overall response rate, defined as the percentage of patients with a complete response (CR) or a partial response (PR).
- adverse events [ Time Frame: 2 year ]Toxicity will be graded according to the NCI-CTCAC version 4.0, from the first day of the first cycle of COPGEM chemotherapy to 30 days after the last dose of study drug.
- Progression-free survival (PFS) [ Time Frame: 2 year ]PFS will be calculated from the start of study drug treatment to the date of disease progression, death, or last follow-up, as appropriate.
- Overall survival (OS) [ Time Frame: 2 year ]OS will be calculated from the start of study drug treatment to the date of disease death or last follow-up, as appropriate.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03052933
|Contact: Deok-Hwan Yangfirstname.lastname@example.org|
|Contact: Ho-Young Yhimemail@example.com|
|Korea, Republic of|
|Chonnam National University Hwasun Hospital||Recruiting|
|Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-809|
|Contact: Deok-Hwan Yang, M.D. and Ph.D. 82-61-379-7636 firstname.lastname@example.org|
|Contact: Kun-Hee Choi, Research Nurse 82-61-379-7717 email@example.com|