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Study of Monalizumab and Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

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ClinicalTrials.gov Identifier: NCT02643550
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : September 13, 2018
Sponsor:
Information provided by (Responsible Party):
Innate Pharma

Brief Summary:

The objective of this study is to evaluate in a 3 +3 design, the safety of escalating doses of Monalizumab given IV in combination with cetuximab in patients who have received prior systemic regimen(s) for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Cohorts expansion will evaluate antitumor activity of the combination.


Condition or disease Intervention/treatment Phase
Head and Neck Neoplasms Biological: Monalizumab Biological: Cetuximab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2 Trial of IPH2201 And Cetuximab in Patients With Human Papillomavirus (HPV) (+) and HPV (-) Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Start Date : December 2015
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: Dose escalation
Dose escalation of monalizumab in combination with cetuximab
Biological: Monalizumab
Five dose levels of Monalizumab will be tested in the dose escalation part: 0.4, 1, 2, 4 and 10 mg/kg every 2 weeks.The patients will then receive the recommended dose for phase 2.
Other Name: IPH2201

Biological: Cetuximab
The first dose of Cetuximab will be 400 mg/m2 IV. All subsequent doses will be 250 mg/m2.

Experimental: Expansion cohort 1
monalizumab + cetuximab expansion cohort
Biological: Monalizumab
Five dose levels of Monalizumab will be tested in the dose escalation part: 0.4, 1, 2, 4 and 10 mg/kg every 2 weeks.The patients will then receive the recommended dose for phase 2.
Other Name: IPH2201

Biological: Cetuximab
The first dose of Cetuximab will be 400 mg/m2 IV. All subsequent doses will be 250 mg/m2.

Experimental: Expansion cohort 2
monalizumab + cetuximab expansion cohort in patients with prior exposure to PD-(L)1 blockers
Biological: Monalizumab
Five dose levels of Monalizumab will be tested in the dose escalation part: 0.4, 1, 2, 4 and 10 mg/kg every 2 weeks.The patients will then receive the recommended dose for phase 2.
Other Name: IPH2201

Biological: Cetuximab
The first dose of Cetuximab will be 400 mg/m2 IV. All subsequent doses will be 250 mg/m2.




Primary Outcome Measures :
  1. Occurrence of Dose Limiting Toxicities (DLT) in the dose escalation part of the study [ Time Frame: within 4 weeks after first administration ]
    To assess the occurrence of Drug Limited Toxicities (DLTs)

  2. Objective Response Rate for expansion cohorts [ Time Frame: up to 12 months ]
    rate of patients in complete or partial response according to RECIST 1.1


Secondary Outcome Measures :
  1. Objective Response Rate for dose escalation part of the study [ Time Frame: up to 12 months ]
    rate of patients in complete or partial response according to RECIST 1.1

  2. Duration of Response for expansion cohorts [ Time Frame: From confirmed response until disease progression, up to 12 months ]
    Duration of complete and partial response

  3. Progression Free Survival for expansion cohorts [ Time Frame: Until disease progression or death, up to 2 years ]
    time between the start of treatment and the first documented progression or death

  4. Overall Survival for expansion cohorts [ Time Frame: Until death, up to 2 years ]
    time between the start of treatment and death



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically or cytologically-confirmed, HPV (+) or HPV (-) squamous cell carcinoma of the nasopharynx (WHO Type 1), oropharynx, hypopharynx, larynx (supraglottis, glottis, subglottis) or oral cavity,
  3. Recurrent or metastatic disease, documented by imaging (CT scan, MRI, X-ray) and/or physical examination. In phase II, measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 is mandated. In phase Ib, patients with or without measurable disease are eligible.
  4. Progression after platinum-based chemotherapy
  5. For phase Ib only: Pretreated patients, and not amenable to further therapy with curative intent.

    This part is open to pretreated patients regardless of the number of previous treatment lines.

    For phase II cohort #1: Patients who received a maximum of two prior systemic regimens for recurrent and/or metastatic disease and not amenable to further therapy with curative intent

    For phase II cohort #2: Patients with R/M SCCHN:

    1. not amenable to therapy of curative intent,
    2. who have received a maximum of two prior systemic regimens in the R/M setting and
    3. who have received prior PD-(L)1 blockers
  6. No prior treatment with cetuximab except if given for primary treatment (i.e., with radiation in locally advanced disease) with no progressive disease for at least 4 months following the end of prior cetuximab treatment
  7. Recovery from prior surgery and recovery from adverse events to grade 1 or less (except alopecia) due to prior radiation therapy and any systemic therapy.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  9. Life expectancy of ≥ 3 months
  10. Patients with treated brain metastases are eligible if they are > 4 weeks from therapy completion (including radiation and/or surgery), are clinically stable at the time of study entry and are not receiving corticosteroid therapy at the time of study entry
  11. Adequate hematologic, immunologic, liver and renal function, defined as a. hemoglobin ≥ 9.0 g/dL, b. absolute neutrophil count ≥ 1,500/mm3, c. platelets ≥ 100,000/mm3, d. total bilirubin ≤ 1.5 X institutional upper normal limit (UNL), e. AST and ALT ≤ 2.5 X institutional UNL, f. serum creatinine ≤1.5 X institutional UNL or estimated (Cockroft-Gault formula) or measured creatinine clearance ≥ 50 mL/min
  12. Negative serum pregnancy test within 72 hours before starting study treatment for women of childbearing potential. Women of childbearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of monalizumab administration and for up to 5 months after the last dose of monalizumab.
  13. Ability to understand a written informed consent document
  14. Signed informed consent prior to any protocol-specific procedures

Exclusion Criteria:

Patients will not be eligible for the study if they fulfil one or more of the following exclusion criteria:

  1. For phase II only: Patients who received more than 2 prior systemic regimens for recurrent and/or metastatic disease (no restriction in the phase Ib part of the trial)
  2. For phase II only: Patients who received cetuximab or another inhibitor of epidermal growth factor receptor are excluded from the phase II of the trial, except if cetuximab was given as a component of the primary treatment with no progressive disease for at least 4 months following the end of prior cetuximab treatment
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab; history of severe or unresolved toxicity to prior treatment with PD-(L)1 blockers (severe AE must have completely resolved or resolved to baseline prior to screening for this study).
  4. Patients with known untreated and uncontrolled brain metastases are excluded. However, brain-imaging studies are not required for eligibility if the patient has no neurological signs or symptoms.
  5. Serious concurrent uncontrolled medical disorder
  6. Auto-immune disease, which

    1. currently or previously required systemic immunosuppressive or immunomodulatory therapy (including corticosteroids administered by systemic route) and/or
    2. has a substantial probability to cause an irreversible injury to any tissue and/or
    3. has been diagnosed less than 3 months before study entry and/or
    4. is clinically unstable and/or
    5. has a substantial risk to progress and cause severe complications
  7. Abnormal cardiac status with any of the following:

    1. Unstable angina
    2. Arrhythmia requiring treatment which is not stabilized by the treatment
    3. QTc > 450 ms (M) or 470 ms (F) (Bazett formula -QT Interval / √ (RR interval) where RR Interval = 60/HR)
  8. History of cardiac dysfunction including any of the following:

    1. Myocardial infarction within the last 6 months
    2. History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  9. Known interstitial lung disease
  10. Pregnant women are excluded from this study; breastfeeding must be discontinued
  11. Other active invasive malignancy (except for treated basal or squamous cell skin carcinoma, or in situ cervix carcinoma)
  12. Treatment with other investigational agents less than 14 days prior to study entry
  13. Systemic treatment with steroids or other immunosuppressive agents within 30 days prior to entry. Physiological replacement with hydrocortisone or equivalent is acceptable
  14. Current active infection
  15. Positive serology for HIV
  16. Positive HBs Ag or positive HBV viremia, Positive HCV viremia
  17. Psychological, familial, sociological, or geographical conditions that do not permit medical follow-up and compliance with study protocol.

Information from the National Library of Medicine

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): NCT02643550


Contacts
Contact: Agnes Boyer Chammard, MD +33430303120 Agnes.BOYER-CHAMMARD@innate-pharma.fr
Contact: Franceline Calmels +33430303062 Franceline.CALMELS@innate-pharma.fr

Locations
United States, California
Stanford Cancer Center Recruiting
Stanford, California, United States, 94305
Contact: Alexander Colevas, MD         
United States, Illinois
university of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Tanguy Lim-Seiwert, MD         
United States, New York
Icahn School of Medicine at Mount Sinaï Recruiting
New York, New York, United States, 10029
Contact: Marshall Posner, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Roger Cohen, MD         
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Jessica Bauman, MD         
France
Centre Oscar Lambret Recruiting
Lille, France
Contact: Gautier Lefebvre, MD         
Centre Leon Berard Recruiting
Lyon, France
Contact: Jerome Fayette, MD         
Hopital La Timone Recruiting
Marseille, France
Contact: Sebastien Salas, MD         
Centre Antoine Lacassagne Recruiting
Nice, France
Contact: Esma Saada Bouzid, MD         
Institut Gustave Roussy Recruiting
Villejuif, France
Contact: Caroline Even, MD         
Sponsors and Collaborators
Innate Pharma

Responsible Party: Innate Pharma
ClinicalTrials.gov Identifier: NCT02643550     History of Changes
Other Study ID Numbers: IPH2201-203
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Antineoplastic Agents