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Nivolumab Plus Pemetrexed for Head and Neck Squamous Cell Carcinoma (NivoPlus)

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. Read our disclaimer for details. Identifier: NCT04107103
Recruitment Status : Unknown
Verified April 2020 by AHS Cancer Control Alberta.
Recruitment status was:  Recruiting
First Posted : September 27, 2019
Last Update Posted : April 21, 2020
Alberta Cancer Foundation
Information provided by (Responsible Party):
AHS Cancer Control Alberta

Brief Summary:
The purpose of this study is to find out what effects the combination of Nivolumab and Pemetrexed has on you and your cancer. The safety of this combination and the effectiveness of this treatment will be studied.

Condition or disease Intervention/treatment Phase
SCCHN Drug: Combination Product: Nivolumab with Pemetrexed Phase 2

Detailed Description:
The treatment of patients with SCCHN is challenging, and represents an area of high unmet need. Treatment options within this patient population are limited, and inadequately treated disease may cause high morbidity, negatively impacting quality of life and leading to increased costs for supportive care. To address the unmet needs of these patients, this exploratory trial combining pemetrexed with standard-of-care nivolumab, with an investigational plan to study clinical and health services outcomes is being proposed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: A single-arm, interventional study combining nivolumab with pemetrexed
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Safety and Feasibility of the Combined Use of Nivolumab With Pemetrexed for the Treatment of Advanced Squamous Cell Carcinoma of the Head and Neck
Actual Study Start Date : March 19, 2020
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : May 30, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Single Arm
A single-arm combining nivolumab with pemetrexed
Drug: Combination Product: Nivolumab with Pemetrexed
Nivolumab 3 mg/kg IV q.2 weekly in combination with pemetrexed 500mg/m2 q.6weekly. Treatment with nivolumab will continue every 14-days, and pemetrexed treatment will continue every 42-days. Treatment continues until disease progression or toxicity resulting in treatment discontinuation or until 2 years of treatment.
Other Names:
  • Opdivo (trade name for Nivolumab)
  • Alimta (brand name for Pemetrexed)

Primary Outcome Measures :
  1. Feasibility [ Time Frame: 1 year after enrollment of last participant ]
    The number of participants who complete at least 2 cycles of combination nivolumab with pemetrexed for the treatment of advanced head and neck cancers, over the total duration of study.

  2. Safety/tolerability (incidence of adverse events including immune related) [ Time Frame: Through study completion up to 2 years ]
    Treatment related and non-related adverse events per CTCAE v.4.0.3 of nivolumab with pemetrexed for the treatment of advanced head and neck cancers. Incidence of adverse events, the number of dose modifications and discontinuations due to adverse events including immune-related adverse events.

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 1 year after enrollment of last participant. ]
    associated with combination nivolumab/pemetrexed therapy (defined as the proportion of participants achieving either a partial response or a complete response as best-overall response per RECIST criteria 1.1)

  2. Progression free survival [ Time Frame: 5 years from final study drug dose. ]
    associated with combination nivolumab/pemetrexed therapy (defined as the time between the date of treatment initiation and the date of disease progression or death (whatever the cause, whichever occurs first)

  3. Overall Survival [ Time Frame: 5 years from final study drug dose. ]
    associated with combination nivolumab/pemetrexed therapy. (Defined as the time between the date of treatment initiation and the date of death)

  4. Patient reported quality of life [ Time Frame: Through study completion, up to 2 years. ]
    associated with combination nivolumab/pemetrexed therapy (measured utilizing the Edmonton Symptom Assessment Score). This questionnaire includes six yes/no questions, 10 questions with a scale of 0 (no symptoms) to 10 (at the worst).

Other Outcome Measures:
  1. Investigation of the role of CD71+ immature red blood cells in the response to treatment with immunotherapy [ Time Frame: 1 year after last study drug dose. ]
    In this study the frequency of the CD71+erythrocyte cells' (blood draws at pre-chemo, post-chemo and post immunotherapy) will be measured.

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.

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

Inclusion Criteria:

  1. Patients must be 18 years of age or older.
  2. Patients must have a diagnosis of histologically confirmed squamous cell carcinoma of the head and neck not amenable to curative intent therapy (surgery or radical chemoradiation).
  3. Patients with squamous cell cancer of the head and neck (SCCHN) who either have a recurrence within 6 months of potentially curative neoadjuvant/adjuvant platinum-based therapy or recurrence after receiving plantium based therapy in a non-curative setting, and who have a good performance status. Nivolumab may also be considered for patients who are ineligible for a platinum-based chemotherapy.
  4. Patients presenting with a diagnosis of HPV-related (p16+) squamous cell carcinoma without an unknown primary will be eligible for enrolment if the investigator deems a head and neck primary to be the most likely primary source.
  5. Patients must be capable of providing consent to enrolment and treatment.
  6. Patients with a performance status of ECOG 0-2(15) will be eligible for enrolment (see appendix 1).
  7. Measurable disease must be present according to RECIST criteria V1.1(16) (see appendix 5).
  8. Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
  9. Patients (men and women) of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 6 months after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

    • Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
  10. Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 30 days after the last dose of study drug.
  11. Male patients should agree to not donate sperm during the study and for a period of at least 6 months after last dose of study drug.
  12. Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
  13. The following adequate organ function laboratory values must be met:


  • Absolute neutrophil count (ANC) >1.5 x109/L
  • Platelet count >100 x109/L
  • Hemoglobin >9 g/dL (may have been transfused)


-Estimated creatinine clearance ≥ 45 mL/min according to the Cockcroft-Gault formula (or l-ocal institutional standard method)


  • Total serum bilirubin <1.5x ULN
  • AST and ALT <2.5x ULN (or ≤ 5 x ULN for patients with documented metastatic disease to the liver)

Exclusion Criteria:

  1. History of pneumonitis requiring treatment with steroids.
  2. History of active interstitial lung disease.
  3. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  4. History of another malignancy or a concurrent malignancy;

    -Exceptions include patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.

  5. Active brain metastases or leptomeningeal disease.

    -Patients with treated brain metastases that are stable for 6 weeks will be eligible for enrolment.

  6. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  7. Prior organ transplantation including allogeneic stem-cell transplantation.
  8. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  9. Active infection requiring systemic therapy.
  10. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE v4.03 Grade ≥ 3).
  11. Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  12. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 grade > 1); however, alopecia, sensory neuropathy ≤ grade 2, or other toxicities ≤ grade 2 not constituting a safety risk based on investigator's judgment are acceptable.

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 identifier (NCT number): NCT04107103

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Contact: Hatim Karachiwala, MD FRCPC 780-832-8290

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Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada
Sponsors and Collaborators
AHS Cancer Control Alberta
Alberta Cancer Foundation
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Principal Investigator: Hatim Karachiwala, MD FRCPC Alberta Health Services - Cross Cancer Institute
Additional Information:
Publications of Results:

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Responsible Party: AHS Cancer Control Alberta Identifier: NCT04107103    
Other Study ID Numbers: Nivo Plus: IIT-0009
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: April 21, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors