Axitinib and Nivolumab for the Treatment of Mucosal Melanoma

NCT05384496 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-017
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The researchers are doing this study to find out whether the combination of axitinib and nivolumab is an effective and safe treatment for people with advanced or metastatic mucosal melanoma that has not been treated before. The researchers think that a combination of axitinib and nivolumab may help people with this disease because both drugs target and block proteins that play a role in cancer cell survival and growth. The researchers think the drugs may be more effective if given in combination rather than on their own.

Conditions

Mucosal Melanoma

Keywords

Axitinib; Nivolumab; PD-1 Blockade; Stereotactic Body Radiotherapy; Ipilimumab; 22-017; head/neck; sinonasal; oral cavity; conjunctival; gastrointestinal; anorectal; esophageal; genitourinary; vulvovaginal; urethral

Outcome Measures

Primary Outcomes (1)

• best objective response

  by RECIST 1.1.The Response Evaluation Criteria in Solid Tumors (RECIST)

  1 year

Study Arms (1)

Axitinib and Nivolumab for the Treatment of Mucosal Melanoma

EXPERIMENTAL

This is a single center trial enrolling up to 20 total evaluable patients with unresectable primary or advanced mucosal melanomas arising from the head and neck, gastrointestinal, or genitourinary tract to receive frontline therapy with nivolumab IV 480mg q4 weeks plus axitinib 5mg PO twice daily. A Simon 2-stage design will be utilized. Upon progression with good tolerance, addition of stereotactive body radiation therapy (SBRT) or CTLA-4 blockade to continued nivolumab plus axitinib will be offered to patients depending on the type of progression. For patients with local or oligometastatic progression, stereotactic body radiotherapy (SBRT) will be added; for patients with progression in a site of prior radiotherapy or with multifocal or distant progression not amenable to SBRT, ipilimumab 1mg/kg IV q3 weeks for up to 4 doses will be added.

Drug: Nivolumab and/or Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: axitinib

Interventions

Nivolumab and/or Ipilimumab DRUG

Combination of nivolumab 3mg/kg IV every 3 weeks with ipilimumab 1mg/kg or nivolumab 480mg IV every 4 weeks as monotherapy is considered standard of care for patients with unresectable locally advanced or metastatic mucosal melanoma.

Axitinib and Nivolumab for the Treatment of Mucosal Melanoma

Stereotactic Body Radiation Therapy (SBRT) RADIATION

SBRT upon local or oligometastatic progression. The prescribed dose of SBRT will be 30 Gy in 5 fractions.

Axitinib and Nivolumab for the Treatment of Mucosal Melanoma

axitinib DRUG

5mg twice daily

Axitinib and Nivolumab for the Treatment of Mucosal Melanoma

Eligibility Criteria

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

You may qualify if:

• Histologic diagnosis of unresectable or advanced mucosal melanoma arising from the head/neck (e.g. sinonasal, oral cavity, conjunctival), gastrointestinal (e.g. anorectal, esophageal), or genitourinary (e.g. vulvovaginal, urethral) sites.
• Measurable disease
• Initial study entry: Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is measurable radiographically (based on RECIST 1.1).
• Triplet arms: assessable disease required. RECIST 1.1 measurable disease is not required.
• Prior therapy
• Initial study entry: No prior systemic therapy (adjuvant or metastatic).
• Triplet arms: Only prior systemic therapy is nivolumab + axitinib on this trial.
• ECOG performance status of 0-2.
• Asymptomatic untreated brain metastases are allowed. Symptomatic brain metastases that have undergone local therapy with RT or surgery and have not required an increase in steroid dose in prior 2 weeks are allowed.
• Screening laboratory parameters:
• White blood cell (WBC) count ≥ 2000/μL;
• Absolute neutrophil count (ANC) ≥ 1500/μL;
• Platelets ≥ 100,000/μL;
• Hemoglobin (Hgb) ≥ 9 g/dL;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN);

You may not qualify if:

• Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (\>10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain- Barre Syndrome, Myasthenia Gravis).
• History of myocarditis.
• History of, or any active evidence of non-infectious pneumonitis
• Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator.
• Cardiovascular disease, including:
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to study entry.
• Current Class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Treatment-refractory hypertension defined as a blood pressure of systolic \>150 mmHg and/or diastolic \>90 mmHg despite adequate attempts at antihypertensive therapy.
• Underlying hematologic issues including:
• Congenital bleeding diathesis
• GI bleeding requiring intervention within the past 6 months
• Active hemoptysis within 42 days prior to study enrollment
• Pulmonary emboli or deep vein thromboses (DVT) that are not stable on anticoagulation regimen.
• History of severe allergic reactions to an unknown allergen or any components of the study drugs.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Pfizer: collaborator

Study Sites (2)

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Radiosurgery; Axitinib

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Alexander Shoushtari, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander Shoushtari, MD

CONTACT

646-888-4161; shoushta@mskcc.org

Christopher Barker, MD

CONTACT

212-639-8168

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single center trial enrolling up to 20 evaluable total patients.

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 20, 2022
• Study Start: May 17, 2022
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (2)