Nivolumab Plus Pemetrexed for Head and Neck Squamous Cell Carcinoma

SCCHN Clinical Trial

— NivoPlus  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04107103
• Other study ID #: Nivo Plus: IIT-0009
• Status: Completed
• Phase: Phase 2
• Start date: March 19, 2020
• Est. completion date: April 28, 2023

Study information

• Verified date: June 2024
• Source: AHS Cancer Control Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 28, 2023
• Est. primary completion date: April 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• SCCHN

Intervention

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.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
AHS Cancer Control Alberta	Alberta Cancer Foundation

Country where clinical trial is conducted

Canada, 

References & Publications (10)

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):6 — View Citation

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. — View Citation

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( — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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 an — View Citation

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 h — View Citation

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;1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Investigation of the role of CD71+ immature red blood cells in the response to treatment with immunotherapy	In this study the frequency of the CD71+erythrocyte cells' (blood draws at pre-chemo, post-chemo and post immunotherapy) will be measured.	1 year after last study drug dose.
Primary	Feasibility	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.	1 year after enrollment of last participant
Primary	Safety/tolerability (incidence of adverse events including immune related)	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.	Through study completion up to 2 years
Secondary	Response Rate	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)	1 year after enrollment of last participant.
Secondary	Progression free survival	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)	5 years from final study drug dose.
Secondary	Overall Survival	associated with combination nivolumab/pemetrexed therapy. (Defined as the time between the date of treatment initiation and the date of death)	5 years from final study drug dose.
Secondary	Patient reported quality of life	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).	Through study completion, up to 2 years.

External Links

•   AHA guidelines website
•   ESC guidelines website