Nivolumab Plus Pemetrexed for Head and Neck Squamous Cell Carcinoma

NCT ID: NCT04107103

Last Updated: 2024-06-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-19

Study Completion Date

2023-04-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

SCCHN

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

A single-arm, interventional study combining nivolumab with pemetrexed
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Single Arm

A single-arm combining nivolumab with pemetrexed

Group Type EXPERIMENTAL

Combination Product: Nivolumab with Pemetrexed

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Opdivo (trade name for Nivolumab) Alimta (brand name for Pemetrexed)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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:

Hematological:

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

Renal:

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

Hepatic:

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Alberta Cancer Foundation

OTHER

Sponsor Role collaborator

AHS Cancer Control Alberta

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Hatim Karachiwala, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

Alberta Health Services - Cross Cancer Institute

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Canada

References

Explore related publications, articles, or registry entries linked to this study.

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. doi: 10.1056/NEJMoa0802656.

Reference Type RESULT
PMID: 18784101 (View on PubMed)

Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015 May;3(5):436-43. doi: 10.1158/2326-6066.CIR-15-0064.

Reference Type RESULT
PMID: 25941355 (View on PubMed)

Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. doi: 10.1054/bjoc.2001.2010.

Reference Type RESULT
PMID: 11531245 (View on PubMed)

Gilbert J, Murphy B, Dietrich MS, Henry E, Jordan R, Counsell A, Wirth P, Yarbrough WG, Slebos RJ, Chung CH. Phase 2 trial of oxaliplatin and pemetrexed as an induction regimen in locally advanced head and neck cancer. Cancer. 2012 Feb 15;118(4):1007-13. doi: 10.1002/cncr.26364. Epub 2011 Jul 15.

Reference Type RESULT
PMID: 21766301 (View on PubMed)

Vermorken JB, Licitra L, Stohlmacher-Williams J, Dietz A, Lopez-Picazo JM, Hamid O, Hossain AM, Chang SC, Gauler TC. Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer. 2013 Sep;49(13):2877-83. doi: 10.1016/j.ejca.2013.05.002. Epub 2013 May 30.

Reference Type RESULT
PMID: 23726971 (View on PubMed)

Davis M, Conlon K, Bohac GC, Barcenas J, Leslie W, Watkins L, Lamzabi I, Deng Y, Li Y, Plate JM. Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in subjects with adenocarcinoma of the pancreas. J Immunother. 2012 Oct;35(8):629-40. doi: 10.1097/CJI.0b013e31826c8a4f.

Reference Type RESULT
PMID: 22996369 (View on PubMed)

Elahi S, Ertelt JM, Kinder JM, Jiang TT, Zhang X, Xin L, Chaturvedi V, Strong BS, Qualls JE, Steinbrecher KA, Kalfa TA, Shaaban AF, Way SS. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection. Nature. 2013 Dec 5;504(7478):158-62. doi: 10.1038/nature12675. Epub 2013 Nov 6.

Reference Type RESULT
PMID: 24196717 (View on PubMed)

Dunsmore G, Bozorgmehr N, Delyea C, Koleva P, Namdar A, Elahi S. Erythroid Suppressor Cells Compromise Neonatal Immune Response against Bordetella pertussis. J Immunol. 2017 Sep 15;199(6):2081-2095. doi: 10.4049/jimmunol.1700742. Epub 2017 Aug 4.

Reference Type RESULT
PMID: 28779022 (View on PubMed)

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

Reference Type RESULT
PMID: 7165009 (View on PubMed)

Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

Reference Type RESULT
PMID: 19934295 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Nivo Plus: IIT-0009

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Iparomlimab and Tuvonralimab in HNSCC
NCT07090317 RECRUITING PHASE2