Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

NCT01693783 | Completed Phase 2 Results DMC

• 8 other identifiers: NCI-2012-02877PHL-0859209N01CM00032N01CM00038N01CM00071U10CA180821UM1CA186705
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 13

Brief Summary

This phase II trial studies how well ipilimumab works in treating patients with human papilloma virus (HPV)-related cervical cancer that has come back or that has spread to other areas of the body. Monoclonal antibodies, such as ipilimumab, can find tumor cells and help kill them or carry tumor-killing substances to them.

Conditions

Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

  Cumulative count of adverse events meeting the criteria of: frequently occurring, serious and severe events of interest.

  Up to 1 year

• Objective Response Rate Using Response Evaluation Criteria in Solid Tumors

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the diameters of target lesions; Overall Response (OR) = CR + PR.

  Up to 1 year

Secondary Outcomes (6)

• Antitumor Activity (Partial Response, Complete Response, and Stable Disease) Using Immune-related Response Criteria (irRC)

  Up to 1 year

• Biologic Responses of Exposure to Ipilimumab by Analysis of Lymphocyte Subsets and Assessment of Cervical Cancer-antigen Specific T Cells Anti-tumor Response

  Up to 1 year

• Disease Stabilization

  Up to 1 year

• Markers of Immune Population, Evaluated in Archival Tissue

  Baseline to 1 year after treatment

• Predictive Value of Baseline C-reactive Protein

  Up to week 3 of course 4

Study Arms (1)

Treatment (ipilimumab)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving objective response or stable disease continue to receive maintenance therapy comprising ipilimumab IV over 90 minutes once every 12 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Treatment (ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic or recurrent cervical cancer of squamous, adenocarcinoma or mixed histology type not suited to definitive localized therapy; HPV status will be confirmed for all patients following enrollment
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \> 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Previous therapy:
• Patients may have undergone surgery and/or received definitive radiation or chemo-radiation for localized disease in the past
• Radiation treatment with curative intent (radical chemoradiotherapy or adjuvant chemoradiotherapy) must have been completed \>= 3 months prior to enrollment
• Note: patients who completed palliative radiation therapy 2 weeks before start of ipilimumab are allowed as long as this does not affect measurable disease
• Patients must have been exposed to platinum chemotherapy either as part of definitive chemo-radiation OR as first line systemic treatment for metastatic disease
• Patients MAY have received up to two prior lines of systemic chemotherapy for metastatic or recurrent disease; patients with metastatic disease at first presentation MUST have received one platinum based line of chemotherapy
• All chemotherapy must have been completed \>= 4 weeks prior to enrollment with radiologic evidence of radiological disease progression
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy of greater than 3 months
• Leukocytes \>= 3.0 x 10\^9/L
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin within normal institutional limits (except in Gilbert's syndrome)

You may not qualify if:

• Patients who have had chemotherapy \< 4 weeks prior to enrollment (\< 6 weeks for nitrosoureas or mitomycin C) or who had radiation therapy with curative intent \< 3 months prior to enrollment (\< 2 weeks for palliative radiation therapy) or those who have not recovered (=\< grade 1) from adverse events related to previous treatments are excluded
• Patients with a history of prior treatment with ipilimumab or other cytotoxic T-lymphocyte antigen 4 (CTLA4) agonists or antagonists, anti-programmed death 1 (PD 1) antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded
• Patients who are receiving any other investigational agents
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and Myasthenia Gravis, multiple sclerosis)
• Patients requiring immunosuppressive agents, unless required for treating potential immune related adverse effects; steroids at their lowest effective dose in patients with radiated brain metastases is permitted
• Patients with known immune impairment who may be unable to respond to anti-CTLA 4 antibody
• Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab
• Patients requiring systemic steroids are excluded; narcotics should be used with caution
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with chronic hepatitis B or hepatitis C infections should be excluded
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ipilimumab
• Patients with active or chronic infection with human immunodeficiency virus (HIV) who have raised viral loads or uncontrolled disease are ineligible; those patients however who exhibit minimal viral loads with good control whilst on stable anti-viral regimen may be considered if they meet all other eligibility criteria

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (13)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer Research Centre

Vancouver, British Columbia, V5Z 1L3, Canada

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Papillomavirus Infections; Uterine Cervical Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

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

Limitations and Caveats

The primary limitation of the trial was the single-arm design. This was a phase 1/2 trial assessing ipilimumab monotherapy with no control arm.

Results Point of Contact

• Title: Dr. Amit Oza
• Organization: University Health Network - Princess Margaret Cancer Centre

Amit.Oza@uhn.ca

416-946-4501

Study Officials

• Amit M Oza

  University Health Network Princess Margaret Cancer Center P2C

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: September 26, 2012
• Study Start: December 3, 2012
• Primary Completion: March 18, 2021
• Study Completion: November 24, 2021
• Last Updated: November 8, 2022
• Results First Posted: November 8, 2022

Record last verified: 2022-10

Locations

US (5); CA (8)