Nivolumab or Expectant Observation Following Ipilimumab, Nivolumab, and Surgery in Treating Patients With High Risk Localized, Locoregionally Advanced, or Recurrent Mucosal Melanoma

NCT03220009 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: NCI-2017-01239A091603U10CA180821
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well nivolumab or expectant observation following ipilimumab, nivolumab, and surgery work in treating patients with high-risk mucosal melanoma that is restricted to the site of origin without evidence of spread, has spread to a local and regional area of the body, or has come back. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Sometimes the mucosal melanoma may not need more treatment until it progresses. In this case, observation may be sufficient. It is not known if nivolumab or expectant observation following ipilimumab, nivolumab, and surgery may be better in treating patients with mucosal melanoma.

Conditions

Cervical Carcinoma; Esophageal Carcinoma; Mucosal Melanoma; Mucosal Melanoma of the Head and Neck; Oral Cavity Mucosal Melanoma; Recurrent Melanoma; Stage II Vulvar Cancer AJCC v7; Stage III Vulvar Cancer AJCC v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IV Oral Cavity Cancer AJCC v6 and v7; Stage IV Vulvar Cancer AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Vaginal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Recurrence free survival (RFS)

  RFS of patients receiving adjuvant nivolumab will be compared to patients undergoing observation. Kaplan- Meier curves will be constructed and median RFS times will be calculated for each arm.

  From randomization to either adjuvant nivolumab or observation until evidence of disease recurrence, assessed up to 5 years

Secondary Outcomes (4)

• Distant recurrence-free survival (DRFS)

  From randomization to either adjuvant nivolumab or observation until a distant recurrence is observed, assessed up to 5 years

• Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 5 years

• Overall survival (OS)

  From randomization to either adjuvant nivolumab or observation until death due to any cause; assessed up to 5 years

• Rate of delayed surgery

  Up to 6 weeks after registration

Other Outcomes (5)

• CD8+ infiltration

  Up to 5 years

• Neoepitope burden

  Up to 5 years

• Pathologic complete response prior to surgery, for patients with imaging available

  Up to time of surgery, assessed up to 5 years

Study Arms (2)

Arm I (nivolumab, ipilimumab, surgery, active surveillance)

ACTIVE COMPARATOR

PART I: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Within 3-6 weeks after receiving nivolumab and ipilimumab, patients undergo surgery per standard of care. Within 84 days of last surgical resection, patients may also undergo adjuvant RT, if clinically appropriate. PART II: Patients undergo active surveillance for 1 year.

Procedure: Conventional Surgery; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Patient Observation; Radiation: Radiation Therapy

Arm II (nivolumab, ipilimumab, surgery, nivolumab)

EXPERIMENTAL

PART I: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Within 3-6 weeks after receiving nivolumab and ipilimumab, patients undergo surgery per standard of care. Within 84 days of last surgical resection, patients may also undergo adjuvant RT, if clinically appropriate. PART II: Patients receive nivolumab IV over 30 minutes once every 2 weeks for 4 doses. Patients then continue to receive nivolumab IV over 30 minutes once every 4 weeks for up to 11 doses in the absence of disease progression or unacceptable toxicity.

Procedure: Conventional Surgery; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Radiation: Radiation Therapy

Interventions

Conventional Surgery PROCEDURE

Undergo surgery

Arm I (nivolumab, ipilimumab, surgery, active surveillance); Arm II (nivolumab, ipilimumab, surgery, nivolumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm I (nivolumab, ipilimumab, surgery, active surveillance); Arm II (nivolumab, ipilimumab, surgery, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (nivolumab, ipilimumab, surgery, active surveillance); Arm II (nivolumab, ipilimumab, surgery, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (nivolumab, ipilimumab, surgery, active surveillance); Arm II (nivolumab, ipilimumab, surgery, nivolumab)

Patient Observation OTHER

Undergo active surveillance

Also known as: Active Surveillance, deferred therapy, expectant management, observation, Watchful Waiting

Arm I (nivolumab, ipilimumab, surgery, active surveillance)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, RADIATION, Radiotherapeutics, radiotherapy, RT, Therapy, Radiation

Arm I (nivolumab, ipilimumab, surgery, active surveillance); Arm II (nivolumab, ipilimumab, surgery, nivolumab)

Eligibility Criteria

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

You may qualify if:

• STEP 1 ELIGIBILITY CRITERIA
• Documentation of disease:
• Histologic documentation: histologically proven mucosal melanoma by local pathology
• Tumor tissue: tumor tissue from the primary site of disease must be available for PD-L1 testing (stratification factor)
• Disease status
• Tumors must have NOT been completely resected, or must be locoregionally recurrent if previously resected; tumor must be deemed potentially resectable by local surgeon
• MM arising from the head/neck, genitourinary, or gastrointestinal tract
• Disease meets any 1 of 4 characteristics:
• Regional lymph node (LN) involvement; OR
• Multifocal/satellite primary disease; OR
• Single localized, primary disease meeting one of the following site-specific requirements:
• Head/neck - any primary lesion if sinonasal; pT4a or above for nasal or oral cavity
• Anorectal - any primary lesion
• Conjunctiva - any primary lesion T2 or T3 stage by American Joint Committee on Cancer (AJCC)
• Vaginal/cervical - any primary

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Alliance for Clinical Trials in Oncology

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Esophageal Neoplasms; Melanoma; Vulvar Neoplasms; Vaginal Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Watchful Waiting; Observation; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Vulvar Diseases; Vaginal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Methods; Investigative Techniques; Therapeutics; Physical Phenomena

Study Officials

• Alexander Shoushtari

  Alliance for Clinical Trials in Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 18, 2017
• Study Start: November 3, 2017
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: October 3, 2018

Record last verified: 2018-10

Locations

US (1)