ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 4 for:    Recruiting, Not yet recruiting Studies | CETUXIMAB AND NIVOLUMAB
Previous Study | Return to List | Next Study

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03370276
Recruitment Status : Recruiting
First Posted : December 12, 2017
Last Update Posted : September 12, 2018
Sponsor:
Collaborators:
James and Esther King Biomedical Research Program
Eli Lilly and Company
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
The purpose of this study is to find out if the combination of two established anti-cancer therapies are beneficial in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Specifically, investigators want to determine if the combination of Cetuximab and nivolumab can help people with advanced cases of HNSCC. Both cetuximab and nivolumab have been used separately to treat HNSCC and are Food and Drug Administration (FDA) approved in this type of cancer.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Oropharynx Squamous Cell Carcinoma of the Larynx Squamous Cell Carcinoma of the Oral Cavity Squamous Cell Carcinoma of the Hypopharynx Squamous Cell Carcinoma of the Paranasal Sinus Head and Neck Squamous Cell Carcinoma Squamous Cell Cancer Head and Neck Carcinoma Drug: Nivolumab Drug: Cetuximab Phase 1 Phase 2

Detailed Description:

PHASE I: Participants will be enrolled sequentially and treated at Dose Level 1, or Dose Level -1, every 2 weeks for 12 cycles or until discontinuation.

Each cycle is 4 weeks. Cetuximab is given alone in lead-in period at Day -14 before Cycle 1 only. In all subsequent doses starting Cycle 1 Day 1, nivolumab and cetuximab will be given concurrently. Dose limiting toxicity (DLT) assessment will be performed during Cycle 1 and will start with the initiation of the combination of cetuximab and nivolumab (4 weeks).

PHASE II: Once the maximum tolerated dose (MTD) or the recommended phase II dose of cetuximab is determined in Phase I, accrual to the phase II will begin.

FOLLOW-UP: Participants will be followed for 2 years from End of Treatment. The imaging studies will be performed every 8 weeks (2 cycles) of the treatments during Cycle 1-6 and then every 12 weeks during Cycle 7-12 as per standard of care. Patient will be followed by treating physicians as per standard of care.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Concurrent Cetuximab and Nivolumab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Actual Study Start Date : December 6, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Phase I - Affiliate Sites Only

Nivolumab and dose escalation of Cetuximab.

Dose Level 1:

Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m^2; Nivolumab 240 mg.

Dose Level -1:

Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m^2; Nivolumab 240 mg.

Drug: Nivolumab
Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.
Other Name: Opdivo

Drug: Cetuximab
Cetuximab intravenously (IV) at 500 mg/m^2 or 250 mg/m^2 as outlined in the treatment arms.
Other Name: Erbitux

Experimental: Phase I - Moffitt Site Only

Nivolumab and dose escalation of Cetuximab.

Dose Level 1:

Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m^2; Nivolumab 240 mg.

Dose Level -1:

Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m^2; Nivolumab 240 mg.

Drug: Nivolumab
Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.
Other Name: Opdivo

Drug: Cetuximab
Cetuximab intravenously (IV) at 500 mg/m^2 or 250 mg/m^2 as outlined in the treatment arms.
Other Name: Erbitux

Experimental: Phase II - Affiliate Sites Only
Nivolumab and Cetuximab at recommended Phase II dose (RP2D).
Drug: Nivolumab
Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.
Other Name: Opdivo

Drug: Cetuximab
Cetuximab intravenously (IV) at 500 mg/m^2 or 250 mg/m^2 as outlined in the treatment arms.
Other Name: Erbitux

Experimental: Phase II - Moffitt Site Only
Nivolumab and Cetuximab at recommended Phase II dose (RP2D).
Drug: Nivolumab
Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.
Other Name: Opdivo

Drug: Cetuximab
Cetuximab intravenously (IV) at 500 mg/m^2 or 250 mg/m^2 as outlined in the treatment arms.
Other Name: Erbitux




Primary Outcome Measures :
  1. Phase I: Recommended Phase 2 Dose (RP2D) [ Time Frame: Up to 12 months ]
    Maximum Tolerated Dose (MTD), or RP2D. The target Dose Limiting Toxicity (DLT) rate is <25%. The MTD will be defined as the dose of cetuximab and nivolumab in which <1 of 3 patients experience a DLT or <2 of 6 patients experience a DLT with the next higher dose having at least 2 patients experiencing a DLT. The MTD is the highest dose at which at most 1 of 6 patients has a DLT. This study will utilize the Cancer Therapy Evaluation Program CTCAE version 4.1 for toxicity and event reporting. Dose-limiting toxicities will be observed until patients have completed Cycle 1 (4 weeks).

  2. Phase II: Overall Survival (OS) Rate [ Time Frame: 1 year post treatment ]
    One year overall survival rate of concurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC. OS: The length of time from the start of treatment until death by any cause.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 24 months post treatment ]
    Complete Response (CR): The disappearance of all measurable lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of measureable lesions, taking as reference the baseline sum longest diameter. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 6 weeks.

  2. Progression Free Survival (PFS) [ Time Frame: Up to 24 months post treatment ]
    Progressive Disease (PD): At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).

  3. Occurrence of Study Treatment Related Adverse Events [ Time Frame: 30 days post protocol treatment ]

    Related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) V4.1. An adverse event (AE) is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product.

    A serious adverse event (SAE) is defined as any AE that results in death, is immediately life-threatening, results in persistent or significant disability/incapacity, requires or prolongs patient hospitalization, is a congenital anomaly/birth defect, or is to be deemed serious for any other reason if it is an important medical event when based on appropriate medical judgement that may jeopardize the patient and may require medical or surgical intervention to prevent one of the other outcomes listed in the above definitions.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, hypopharynx, or larynx. Squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive.
  • Must have recurrent or metastatic HNSCC stage III/IV that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).Patients with persistent disease following radiation therapy administered with a chemotherapy sensitizer may also be included.
  • Must have progressed on at least one prior line of chemotherapy, targeted therapy, palliative radiation, and/or biological therapy regimen for their recurrent and/or metastatic HNSCC. However, if patients are likely to be intolerant to standard first-line systemic chemotherapy, the patients are eligible to enroll to this study as the first-line therapy. Additionally, patients with persistent disease or platinum-refractory recurrent disease may enroll in this study as a first-line therapy.
  • Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in RECIST version 1.1.
  • Must be ≥ 18 years of age.
  • Life expectancy of greater than 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Must have normal organ function: Absolute neutrophil count > 1,500/μL; Hemoglobin > 9 g/dL; Platelets > 100,000/μL; Total bilirubin ≤ 1.5 mg/dL X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) < 3 X institutional ULN (or 5.0 X the ULN in the setting of liver metastasis); Serum creatinine of ≤ 1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula): Female creatinine clearance = (140 - age in years) x weight in kg x 0.8572 x serum creatinine in mg/ dL; Male creatinine clearance = (140 - age in years) x weight in kg x 1.0072 x serum creatinine in mg/dL.
  • Participants, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Have experienced grade 3 or above skin toxicity from prior Epidermal growth factor receptor (EGFR) inhibiting therapy.
  • Have experienced grade 3 or above toxicity from prior anti-PD1 therapy.
  • Have p16 negative squamous cell carcinoma of unknown primary in cervical lymph node.
  • Patients with primary nasopharynx or salivary gland cancers.
  • Patients who have had chemotherapy, biological therapy or definitive radiation within 4 weeks of the study enrollment or those who have not recovered from adverse events to ≤ Grade 1 due to agents administered more than 4 weeks earlier.
  • Had undergone any major surgery within 4 weeks of study enrollment.
  • Had undergone any palliative radiation within 2 weeks of study enrollment.
  • Have had other investigational agents within 4 weeks or 5 half-lives, whichever is shorter, of the study enrollment.
  • Have known leptomeningeal metastases or untreated or symptomatic brain metastases. Treated, asymptomatic brain metastasis can be included.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease requiring systemic steroids, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Have clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
  • Have uncontrolled or poorly controlled hypertension (>180 mmHg systolic or > 130 mmHg diastolic) at the time of enrollment.
  • Prior treatment with a combination of cetuximab and a PD-1/PD-L1 inhibitor. Prior treatment with cetuximab or a PD-1/PD-L1 inhibitor is allowed as long as not previously given in combination.
  • A history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab and/or nivolumab.
  • Pregnant or breast-feeding.
  • Known active HIV, Hep B, or Hep C infection. If not clinically indicated, the patients do not need to be tested.

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): NCT03370276


Contacts
Contact: Matthew Johnson 813-745-5434 matthew.johnson@moffitt.org
Contact: Christine H. Chung, M.D. 813-745-5431 christine.chung@moffitt.org

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Matthew Johnson    813-745-5434    matthew.johnson@moffitt.org   
Principal Investigator: Christine H. Chung, M.D.         
Sub-Investigator: Julie Kish, M.D.         
Sub-Investigator: Jameel Muzaffar, M.D.         
United States, Georgia
Emory University School of Medicine Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Nabil Saba, M.D.    404-778-3126    nfsaba@emory.edu   
Sub-Investigator: Nabil Saba, M.D.         
United States, Ohio
The Ohio State University Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: James Rocco, M.D., Ph.D.    614-293-8074    James.Rocco@osumc.edu   
Sub-Investigator: James Rocco, M.D., Ph.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
James and Esther King Biomedical Research Program
Eli Lilly and Company
Bristol-Myers Squibb
Investigators
Principal Investigator: Christine H. Chung, M.D. H. Lee Moffitt Cancer Center and Research Institute

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT03370276     History of Changes
Other Study ID Numbers: MCC-19178
First Posted: December 12, 2017    Key Record Dates
Last Update Posted: September 12, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Head and Neck Neoplasms
Paranasal Sinus Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Nose Neoplasms
Nose Diseases
Respiratory Tract Diseases
Paranasal Sinus Diseases
Respiratory Tract Neoplasms
Nivolumab
Cetuximab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs