Assessment of nivolumab and metronomic as palliative Treatment in head and neck cancer patients

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2020/11/028953
• Date of registration: 06-11-2020
• Prospective Registration: Yes
• Primary sponsor: Tata Memorial Hospital
• Public title: Assessment of nivolumab and metronomic as palliative Treatment in head and neck cancer patients
• Scientific title: Phase 2 going to phase 3 randomized study for evaluation of nivolumab and metronomic as palliative therapy in head and neck cancer.
• Date of first enrolment: 17-11-2020
• Target sample size: 184
• Recruitment status: Not Yet Recruiting
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=48487
• Study type: Interventional
• Study design: Randomized, Parallel Group Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:On-site computer system Blinding and masking:Not Applicable
• Phase: Phase 2/ Phase 3

Countries of recruitment

India

Contacts

• Name: Dr Vijay M Patil
• Affiliation: Tata Memorial Hospital

• Name: Dr Vijay M Patil
• Affiliation: Tata Memorial Hospital

Key inclusion & exclusion criteria

Inclusion criteria: 1. Subjects must have head and neck squamous cell carcinoma and must have been planned for palliative systemic therapy

2. Age: Male or female subjects aged >= 18 years. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

4. Subjects must have normal organ and marrow function as defined below:

a. Hematologic: Absolute neutrophil count (ANC) >= 1.0 Ã? 109/L, platelet count >= 100 Ã? 109/L, and hemoglobin >= 8 g/dL (may have been transfused). b. Hepatic: Total bilirubin level <= 1.5 Ã? the upper limit of normal (ULN) range and AST and ALT levels <= 2.5 Ã? ULN or AST and ALT levels <= 5 x ULN (for subjects with documented metastatic disease to the liver).

c. Renal: Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula. 5. Presence of at least one measurable lesion as defined by RECIST version 1.1.

6. Patients with HIV are potentially eligible, as long as they have a CD4 count > 200, are on concurrent HAART (highly active antiretroviral therapy), and absence of active AIDS defining conditions.

7. Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential.

8. Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last Nivolumab treatment administration if the risk of conception exists. The effects of Nivolumab on the developing human fetus are teratogenic. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

9. Both men and women of all races and ethnic groups are eligible for this study.

10. Willing and able to comply with all study requirements, including treatment, able to be followed up at regular intervals and/or nature of required assessments.

11. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria: 1. Subjects who are receiving any other current investigational agents.

2. Within 3 weeks of administration of chemotherapeutic agent.

3. IMMUNOSUPPRESSANTS: 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) d. Steroids for raised intracranial pressure due to the disease itself e,Steroid use for avoidance or treatment of emesis.

4. AUTOIMMUNE DISEASE: Active autoimmune disease that might deteriorate when receiving a chemotherapeutic agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.

5. ORGAN TRANSPLANTATION: Prior organ transplantation including allogeneic stem-cell transplantation.

6. INFECTIONS: Active infection requiring systemic therapy.

7. HEPATITIS: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen if there is a raised HBV DNA or HCV RNA if anti-HCV antibody screening test positive.Mere presence of HBV or HCV at screening test wont rule the patient out).

8. VACCINATION: Vaccination within 4 weeks of the first dose of Nivolumab and while on study is prohibited except for administration of inactivated vaccines.

9. HYPERSENSITIVITY TO STUDY DRUG: Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI-CTCAE v4.03 Grade >= 3).

10. CARDIOVASCULAR DISEASE: Clinically significant (i.e., active) cardiovascular disease: cerebrovascular 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.

11. OTHER PERSISTING TOXICITIES: Persisting toxicity related to prior therapy (NCI-CTCAE v4.03 Grade 1); however, alopecia, sensory neuropathy Grade <= 2, or other Grade <= 2 not constituting a safety risk based on Investigatorâ??s judgment is acceptable.

12. Other severe acute or chronic medical conditions including immune colitis, 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.

13. Pregnant women are excluded from this study. Based on its mechanism of action. Nivolumab can cause foetal harm when administered to a pregnant woman. Therefore, potential risks of administering Nivolumab during pregnancy include increased rates of abortion or stillbirth. Advise females of reproductive potential to use effective contraception during treatment and for at least one month after the last dose of Nivolumab.

14. Lactating females: There is no information regarding the presence of Nivolu

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: C00-C14- Malignant neoplasms of lip, oral cavity and pharynx Health Condition 2: C00-D49- Neoplasms

Intervention(s)

Intervention1: Nivolumab Therapy Arm: Nivolumab- Inj Nivolumab 20 mg in 100 ml NS over 60 minutes every 3 weekly will be administered with standard of care chemotherapy.
Control Intervention1: Standard of care chemotherapy: Chemotherapy will be administered with tablet erlotinib 150 mg ( fixed dose ) PO OD daily, capsule celecoxib 200 mg ( fixed dose ) PO BD daily and oral weekly methotrexate 9 mg/m2. All chemotherapy medications will be taken 1 hour before breakfast. The methotrexate is available in 2.5 mg tablets. Hence the dose of methotrexate will be rounded of to the nearest lower numerical which is a multiple of 2.5. This could enable delivery of methotrexate without the need for breaking or crushing the tablets. All methotrexate tablets will be taken together. It will be a 21 day cycle

Primary Outcome(s)

To compare the overall survival.Timepoint: 5 years

Secondary Outcome(s)

1.To compare the progression free survival

2. To compare the overall response rate post 2 cycles according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

3. To assess and compare the safety and tolerability

4. To compare the quality of life

Timepoint: 5 years

To do a biomarker analysis to identify genetic signatures predicting responseTimepoint: 5 years

Secondary ID(s)

900663

Version No 2.0 Dated 26th August 2020

Source(s) of Monetary Support

Tata Memorial Hospital

Ethics review

Status: Approved
Approval date: 08/10/2020
Contact:

Institutional Ethics Committee