Copanlisib in Association With Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinomas Harboring a PI3KCA Mutation/Amplification and/or a PTEN Loss (COPAN-ORL06)
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|ClinicalTrials.gov Identifier: NCT02822482|
Recruitment Status : Active, not recruiting
First Posted : July 4, 2016
Last Update Posted : April 3, 2019
The study consists of two distinct and sequential parts:
- A Phase Ib aimed at determining the MTD (Maximum Tolerated Dose) of the combination (copanlisib/cetuximab) and the RP2D
- A Phase II aimed at evaluating the efficacy of the combination at the RP2D (Recommended Phase 2 Dose)
All patients will be treated with the Copanlisib, a selective PI3KCA inhibitor, in association with Cetuximab.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Squamous Cell of Head and Neck||Drug: Copanlisib Drug: Cetuximab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase ib/II Trial of Copanlisib, a Selective PI3K Inhibitor, in Combination With Cetuximab in Patients With Recurrent and/or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) Harboring a PI3KCA Mutation/Amplification and/or a PTEN Loss.|
|Actual Study Start Date :||June 2016|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||June 2020|
Experimental: Copanlisib + Cetuximab
All patients will be treated by Copanlisib in association with Cetuximab.
Copanlisib will be given at Day 1, Day 8 and Day 15 (1 cycle = 28 days), administered intravenously over 60 minutes, in association with Cetuximab.
Other Name: BAY 80-6946
Cetuximab will be given weekly at Day 1, Day 8, Day 15 and Day 22 (1 cycle = 28 days), administered intravenously over 120 minutes (Cycle 1 Day 1) or 60 minutes (subsequent infusions), in association with Copanlisib.
Other Name: Erbitux
- Phase Ib (dose escalation phase): to determine the Maximal Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Copanlisib in association with Cetuximab [ Time Frame: 1 month ]Determination of the MTD will be based on the occurence of Dose Limiting Toxicities during Cycle 1.
- Phase II (expansion phase) : to assess the efficacy of the combination (Copanlisib + Cetuximab) at the RP2D. [ Time Frame: 16 weeks ]Efficacy of the combination will be assessed through Progression Free Survival at week 16.
- Efficacy of the combination [ Time Frame: Through the study completion with an average of 10 months ]Objective Response Rate (ORR) using RECIST 1.1 criteria
- Efficacy of the combination [ Time Frame: Through the study completion with an average of 10 months ]Overall Survival (OS)
- Adverse Events (NCI CTCAE v4.0) [ Time Frame: Up to 15 cycles ]All Adverse Events (NCI CTCAE v4.0), related or not related to Copanlisib or Cetuximab, will be collected in the Case Report Form in order to picture the safety profile of the association.
- Copanlisib Maximum Plasma Concentration [Cmax] [ Time Frame: First Month (at Day 1 and Day 15) ]For patients enrolled in the phase Ib (dose escalation phase) pharmacokinetic samples (blood) will be collected at Cycle 1 Day 1 and Cycle 1 Day 15. There will be 5 samples per day: pre-infusion, end of infusion, 2 hours, 8 hours and 24 hours after the start of Copanlisib infusion.
- Area Under the Curve [AUC] for Copanlisib pharmacokinetic [ Time Frame: First Month (at Day 1 and Day 15) ]For patients enrolled in the phase Ib (dose escalation phase) pharmacokinetic samples (blood) will be collected at Cycle 1 Day 1 and Cycle 1 Day 15. There will be 5 samples per day: pre-infusion, end of infusion, 2 hours, 8 hours and 24 hours after the start of Copanlisib infusion.
- Mutational profile of circulating tumoral DNA (ctDNA) [ Time Frame: through the study duration: baseline, C1D1, C1D15, 8 weeks, disease progression ]For patients enrolled in the phase II (dose escalation phase) blood samples will be collected at baseline, C1D1, C1D15, 8 weeks, Disease progression or end of treatment whichever comes first.
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): NCT02822482
|Institut de Cancérologie de l'Ouest|
|Angers, France, 49933|
|Centre Georges François Leclerc|
|Dijon, France, 21079|
|Centre Oscar Lambret|
|Lille, France, 59020|
|Centre Léon Bérard|
|Lyon, France, 69437|
|Institut de Cancérologie de Lorraine|
|Nancy, France, 54511|
|Centre Antoine Lacassagne|
|Nice, France, 06189|
|Paris, France, 75005|