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

NCT02822482 | Terminated Phase 1 DMC

• 2 other identifiers: UC-0130/15072015-004340-19
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Carcinoma, Squamous Cell of Head and Neck

Outcome Measures

Primary Outcomes (2)

• 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

  Determination of the MTD will be based on the occurence of Dose Limiting Toxicities during Cycle 1.

  1 month

• Phase II (expansion phase) : to assess the efficacy of the combination (Copanlisib + Cetuximab) at the RP2D.

  Efficacy of the combination will be assessed through Progression Free Survival at week 16.

  16 weeks

Secondary Outcomes (6)

• Efficacy of the combination

  Through the study completion with an average of 10 months

• Efficacy of the combination

  Through the study completion with an average of 10 months

• Adverse Events (NCI CTCAE v4.0)

  Up to 15 cycles

• Copanlisib Maximum Plasma Concentration [Cmax]

  First Month (at Day 1 and Day 15)

• Area Under the Curve [AUC] for Copanlisib pharmacokinetic

  First Month (at Day 1 and Day 15)

Study Arms (1)

Copanlisib + Cetuximab

EXPERIMENTAL

All patients will be treated by Copanlisib in association with Cetuximab.

Drug: Copanlisib; Drug: Cetuximab

Interventions

Copanlisib DRUG

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.

Also known as: BAY 80-6946

Copanlisib + Cetuximab

Cetuximab DRUG

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.

Also known as: Erbitux

Copanlisib + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with R/M HNSCC (oropharynx, oral cavity, hypopharynx and larynx), histologically or cytologically confirmed, not amenable to curative treatment with surgery and/or chemotherapy and/or radiotherapy (Stage III/IV)
• Adult men and women ≥ 18 years
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Patients with tumor harboring a PI3K mutation/amplification and/or a PTEN loss
• Patients with a radiologic documented progression or relapse after cetuximab therapy (patients could have either received combination platinum doublet with cetuximab or cetuximab after platinum doublet)
• Patients with prior platinum based therapy, unless contraindicated
• Patients with at least one measurable lesion assessed by Magnetic Resonance Imaging (MRI) or a computerized tomography scanner (CT-scan) according to RECIST v1.1. Patients must have clinically and/or radiographically documented measurable disease. At least one site of disease must be unidimensionally measurable as follows
• CT-scan, physical exam ≥ 10 mm
• Lymph node short axis ≥ 15 mm Tumor measurements must be performed within 28 days prior to starting study drug
• Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies since signing of the informed consent form and up to 12 months (for women of child bearing potential) and 6 months (for fertile men) after the last study drug administration (Copanlisib). Highly effective contraception methods are detailed in section 7.2
• Women of childbearing age or sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine within the 7 days prior to starting study drug)
• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
• Patients with social insurance coverage

You may not qualify if:

• Patients previously treated with PI3K and/or mTOR inhibitors
• Patients with anticancer therapy (radiotherapy, immunotherapy, chemotherapy, etc.) within 28 days or investigational treatment within 28 days prior to the initiation of study drug treatment, unless evidence of progression since last treatment
• Patients currently using other approved or investigational anti-neoplasic agent
• Patients with uncontrolled arterial hypertension despite optimal medical management, Congestive heart failure \> New York Heart Association (NYHA) class 2, Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of test drug No active cardiac disease including any of the following: left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO) and QTc \> 470 ms on screening ECG
• Patients with uncontrolled diabetes mellitus (patients with controlled Type I or II diabetes mellitus will be eligible but only into the phase II of the study and only if fasting HbA1c ≤ 8.5% at screening)
• Patients with a history of Human Immunodeficiency Virus (HIV) Hepatitis B (HBV) or hepatitis C (HCV) infection. All patients must be screened for HIV, HBV and HCV up to 28 days prior to first dosing using the routine virus laboratorial panel. Patients who are positive for HBs Ag or HBc Ab will be eligible if they are negative for HBV-DNA. Patients who are positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA
• Patients with active uncontrolled or symptomatic central nervous system (CNS) metastases. Patients are eligible if their disease is controlled at least 30 days on corticosteroids prior to starting study drug
• Patients with major surgery within 28 days, or open biopsy within 7 days, prior to starting study drug. Patients must have recovered from major side effects of the surgery
• Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible. Copanlisib is primarily metabolized by CYP3A4. Therefore concomitant use of strong inhibitors of CyP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, st. John's Wort) are not permitted from Day -14 of Cycle 1 until the Safety follow up visit
• Patients with altered hematopoietic or organ function, as indicated by the following criteria (assessed within 7 days prior the first dosing):
• Absolute granulocytes \< 1.0 x 10⁹/L
• Platelets \< 75 x 10⁹/L
• ALAT/ASAT \> 2.5 x ULN in the absence of or \> 5 x ULN in the presence of liver metastases
• Bilirubin \> 1.5 x ULN (except Gilbert Syndrome: \< 3.0 mg/dL)
• Creatinine clearance \< 60 mL/min (measured or calculated by Cockcroft and Gault formula) or serum creatinine \> 1.0 x ULN

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (7)

Institut de Cancérologie de l'Ouest

Angers, 49933, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69437, France

Location

Institut de Cancérologie de Lorraine

Nancy, 54511, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Related Publications (1)

• Marret G, Isambert N, Rezai K, Gal J, Saada-Bouzid E, Rolland F, Chausson M, Borcoman E, Alt M, Klijanienko J, Vansteene D, Guigay J, Kamal M, Bieche I, Le Tourneau C; UNICANCER Head, Neck Group. Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Invest New Drugs. 2021 Dec;39(6):1641-1648. doi: 10.1007/s10637-021-01152-z. Epub 2021 Jul 28.

  PMID: 34322775 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

copanlisib; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: July 4, 2016
• Study Start: June 1, 2016
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: March 29, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)