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Carcinoma, Squamous Cell of Head and NeckPhase 1/2COPAN-ORL06NCT02822482

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

A Phase 1/2 study testing Copanlisib and Cetuximab in people with Carcinoma, Squamous Cell of Head and Neck, run by UNICANCER at 7 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Copanlisib and Cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
7 sitesFrance
Study dates
Jun 2016to 9 Oct 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula (within 7 days prior to starting study drug). If not on target, this evaluation may be repeated once after at least 24 hours either according to the MDRD abbreviated formula or by 24 hour sampling. If the later result is within acceptable range, it may be used to fulfill the inclusion criteria instead

Who cannot join

  • 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
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  • 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
  • Lipase > 1.5 x ULN
  • INR and PTT > 1.5 x ULN
  • Patients with a history of hypersensitivity to other monoclonal antibodies or to the active or inactive excipients of study drug
  • Known drug or alcohol abuse
  • Known or underlying medical condition that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events
  • History of uncontrolled seizures, seizure disorder requiring medication, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake
  • Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study
  • Individuals deprived of liberty or placed under the authority of a tutor
  • Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated:
  • Cervical carcinoma in situ
  • Non-melanoma skin cancer
  • Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria])
  • Localized prostate cancer
  • Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication
  • Proteinuria of ≥ CTCAE Grade 3 as assessed by a 24h protein quantification or estimated by urine protein-creatinine ratio > 3.5 on a random urine sample
  • History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
  • Concurrent diagnosis of pheochromocytoma
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment
  • Unresolved toxicity higher than CTCAE Grade 1 attributed to any prior therapy/procedure, excluding alopecia
  • Ongoing immunosuppressive therapy
  • Blood or platelets transfusion less than 7 days before starting treatment
  • Myeloid growth factors within 14 days prior to treatment
  • Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed. Previous corticosteroid therapy must be stopped or reduced to the allowed dose 7 days before performing the screening CT scan/MRI, whichever is performed first, and again prior to the first study drug administration. If a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose after the patient has signed the IC. Patients may be using topical or inhaled corticosteroids
  • History of having received an allogeneic bone marrow or organ transplant
  • Anti-arrhythmic therapy (beta blockers or digoxin are permitted)

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • Institut de Cancérologie de l'Ouest

    Angers, 49933

  • Centre Georges François Leclerc

    Dijon, 21079

  • Centre Oscar Lambret

    Lille, 59020

  • Centre Léon Bérard

    Lyon, 69437

  • Institut de Cancérologie de Lorraine

    Nancy, 54511

  • Centre Antoine Lacassagne

    Nice, 06189

  • Institut Curie

    Paris, 75005

Other trials in France

About this study

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.

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.

Being tested
Copanlisib, Cetuximab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CopanlisibDrug

    Also called BAY 80-6946

    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.

  • CetuximabDrug

    Also called Erbitux

    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.

Study groups in NCT02822482
Study groupRoleWhat they receive
Copanlisib + CetuximabExperimentalAll patients will be treated by Copanlisib in association with Cetuximab.
Receives: Drug: Copanlisib; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 month

  2. 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.

    Measured: 16 weeks

Secondary outcomes (6)

  1. Efficacy of the combination

    Objective Response Rate (ORR) using RECIST 1.1 criteria

    Measured: Through the study completion with an average of 10 months

  2. Efficacy of the combination

    Overall Survival (OS)

    Measured: Through the study completion with an average of 10 months

  3. Adverse Events (NCI CTCAE v4.0)

    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.

    Measured: Up to 15 cycles

  4. Copanlisib Maximum Plasma Concentration [Cmax]

    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.

    Measured: First Month (at Day 1 and Day 15)

  5. Area Under the Curve [AUC] for Copanlisib pharmacokinetic

    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.

    Measured: First Month (at Day 1 and Day 15)

  6. Mutational profile of circulating tumoral DNA (ctDNA)

    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.

    Measured: through the study duration: baseline, C1D1, C1D15, 8 weeks, disease progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jul 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion9 Oct 2019
  4. Study completion9 Oct 2019

Why it stopped: futilty of the treatment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02822482
Sponsor's protocol ID
UC-0130/1507
Other IDs
2015-004340-19, 2015
Acronym
COPAN-ORL06
Status last verified
Mar 2021
First submitted
16 Jun 2016
Last updated
29 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Publications

  • 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.

    PubMed 34322775

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Copanlisib and Cetuximab in people with Carcinoma, Squamous Cell of Head and Neck, run by UNICANCER at 7 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: futilty of the treatment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02822482, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2021.

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