Sitravatinib (MGCD516) and Nivolumab in Oral Cavity Cancer Window Opportunity Study

NCT03575598 | Completed Early Phase 1 FDA Drug

• 1 other identifier: SNOW-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative drugs, Sitravatinib and Nivolumab.

Conditions

Squamous Cell Carcinoma, Head And Neck; Squamous Cell Carcinoma Mouth; Squamous Cell Carcinoma of the Oral Cavity

Outcome Measures

Primary Outcomes (3)

• Pharmacodynamic and immune effects of pre-operative therapy with Sitravatinib and Nivolumab in patients with SCCOC

  Tumor PD-L1 expression by IHC

  2 years

• Pharmacodynamic and immune effects of pre-operative therapy with Sitravatinib and Nivolumab in patients with SCCOC

  Density of immune cell population in the tumor and/or peripheral blood, including circulating tumor DNA (ctDNA), T-cell subsets, NK cells and myeloid-derived cell subsets

  2 years

• Pharmacodynamic and immune effects of pre-operative therapy with Sitravatinib and Nivolumab in patients with SCCOC

  Serum pro-inflammatory cytokines and chemokines

  2 years

Secondary Outcomes (7)

• Safety and tolerability of pre-operative therapy with Sitravatinib and Nivolumab on patients with SCCOC

  2 years

• Safety and tolerability of pre-operative therapy with Sitravatinib and Nivolumab on patients with SCCOC

  2 years

• Safety and tolerability of pre-operative therapy with Sitravatinib and Nivolumab on patients with SCCOC

  2 years

• Pre-operative clinical activity of the combination of Sitravatinib and Nivolumab in patients with SCCOC

  2 years

• Pre-operative clinical activity of the combination of Sitravatinib and Nivolumab in patients with SCCOC

  2 years

Other Outcomes (4)

• Dynamic changes in immune cell activation and/or suppression using flow cytometry, DNA/RNA sequencing, and FACS sorting

  2 years

• Dynamic changes in immune cell activation and/or suppression using flow cytometry, DNA/RNA sequencing, and FACS sorting

  2 years

• Dynamic changes in immune cell activation and/or suppression using flow cytometry, DNA/RNA sequencing, and FACS sorting

  2 years

Study Arms (1)

Sitravatinib and Nivolumab

EXPERIMENTAL

Patients will start therapy with sitravatinib within 10 days of study enrollment. Sitravatinib will be given at 120mg once daily on a continuous basis until 48 hours before planned surgery, or for a maximum period of 28 days. Nivolumab will be given as a single infusion at a dose of 240mg, over a period of 30 minutes on Day 15 of the study.

Drug: Sitravatinib; Biological: Nivolumab

Interventions

Sitravatinib DRUG

Sitravatinib (MGCD516) is an orally-available, potent small molecule inhibitor of a closely related spectrum of tyrosine kinases, which has shown antitumor activity in a variety of in vitro and in vivo model systems.

Also known as: MGCD516

Sitravatinib and Nivolumab

Nivolumab BIOLOGICAL

Nivolumab (OPDIVO®) is a human IgG4 kappa immunoglobulin that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Also known as: OPDIVO®

Sitravatinib and Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written and voluntary informed consent.
• Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Age \> 18 years, male or female.
• Patient must be diagnosed with histologically confirmed squamous cell carcinoma of the oral cavity (SCCOC) (floor of mouth, anterior 2/3 tongue, buccal mucosa, upper and lower gingiva, retromolar trigone and hard palate) previously untreated, considered resectable by the head and neck treating surgeon (T2-4a, N0-2, or T1 - greater than 1 cm - N2, M0; without evidence of distant metastasis).
• Patient must be willing and able to provide 2 fresh tumor biopsies for histopathological and biomarker evaluation: one at baseline and one after treatment with Sitravatinib but prior to treatment with Nivolumab. Archival tissue sample will be requested if available.
• No anti-neoplastic treatment is allowed between the time from obtaining baseline tumor specimen and enrollment.
• ECOG performance status 0-1.
• Patient must have adequate organ function as determined by the following:
• Renal function: i. Serum creatinine \< 1.5 ULN (upper limit of normal range) or a calculated creatinine clearance of \> 50mL/min using the following formula:
• Creatinine clearance = \[(140-age) x wt (kg) x Constant\*\] / creatinine (umol/L)
• \*Constant = 1.23 for men, and 1.04 for women
• Bone marrow function (without hematopoietic growth factors or transfusion): i. Absolute neutrophil count (ANC) \> 1.0 x 109/L ii. Leukocytes \> 2.0 x 109/L iii. Hemoglobin \> 90 g/L or \> 9g/dL iv. Platelets \> 100 x 109/L
• Liver function: i. Total bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN for patients with Gilbert Syndrome. ii. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \< 2.5 x ULN
• Cardiac function: i. A normal left ventricular ejection fraction (LVEF) of ≥50% by a MUGA scan performed within 4 weeks of the study commencement.
• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

You may not qualify if:

• Primary site of head and neck carcinoma unknown, lip, skin, or outside the oral cavity.
• Patients with tumors that invade major vessels or are within ≤ 3 mm of the carotid artery as shown unequivocally by imaging studies.
• Patients with any prior history of clinically significant bleeding related to the current head and neck cancer.
• Patients with a history of gross hemoptysis (bright red blood of ½ teaspoon or more per episode of coughing) \< 3 months prior to enrollment.
• Prior or concurrent radiation therapy to tumor at site of planned resection.
• Any concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment.
• Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• Current or prior use of immunosuppressive medication within 14 days prior to starting dosing. The following are exceptions to this criteria:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
• Adrenal replacement steroid \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Steroids as premedication for hypersensitivity reactions (eg, computed tomography scan premedication).
• Active or documented history of autoimmune disease within 2 years before screening, including:
• Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis).
• Patients with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic steroids and/or immunosuppressive agents within the past 2 years, are not excluded.
• History of primary immune deficiency.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Oliva M, Chepeha D, Araujo DV, Diaz-Mejia JJ, Olson P, Prawira A, Spreafico A, Bratman SV, Shek T, de Almeida J, R Hansen A, Hope A, Goldstein D, Weinreb I, Smith S, Perez-Ordonez B, Irish J, Torti D, Bruce JP, Wang BX, Fortuna A, Pugh TJ, Der-Torossian H, Shazer R, Attanasio N, Au Q, Tin A, Feeney J, Sethi H, Aleshin A, Chen I, Siu L. Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study. J Immunother Cancer. 2021 Oct;9(10):e003476. doi: 10.1136/jitc-2021-003476.

  PMID: 34599023 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

sitravatinib; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lillian Siu, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: July 2, 2018
• Study Start: August 30, 2018
• Primary Completion: February 18, 2020
• Study Completion: February 18, 2020
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)