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Cervical AdenocarcinomaPhase 2NCT01693783

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

A Phase 2 study testing Ipilimumab and Laboratory Biomarker Analysis in people with Cervical Adenocarcinoma and Cervical Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Ipilimumab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
13 sitesin 2 countries
Study dates
3 Dec 2012to 24 Nov 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Thyroid stimulating hormone (TSH) =< upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine < 1.25 ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 as calculated by the Cockcroft and Gault formula
  • All radiology studies must be performed =< 3 weeks prior to the start of therapy
  • Subjects with treated and asymptomatic brain metastases are eligible; patients that received palliative radiation (for brain metastases) are eligible if they have been asymptomatic for at least 2 weeks with use of maintenance steroid therapy, and last received radiation at least 4 weeks prior to start of therapy
  • Ability to understand and willing to sign a written informed consent document
  • Ongoing prior toxicities related to previous treatments must be recovered to =< grade 1 at the time of registration (with the exception of alopecia or skin depigmentation)
  • Patients are willing to undergo tumor biopsy pre-treatment (within 14 days prior to registration) and post-treatment (within the first week of cycle 2 onset); patients who consent but have tumor that is not amenable to safe biopsy will be allowed to enter the trial/continue therapy as per protocol if this has been addressed and permission is granted from the lead consortium principal investigator (PI) prior to registration continuation of treatment

Who cannot join

  • 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
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  • 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

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

Canada8 sites
  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Ottawa Hospital and Cancer Center-General Campus

    Ottawa, Ontario, K1H 8L6

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BC Cancer Research Centre

    Vancouver, British Columbia, V5Z 1L3

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

United States5 sites
  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • City of Hope South Pasadena

    South Pasadena, California, 91030

Other trials in United States

About this study

Official title: A Phase 2 Study of Ipilimumab in Women With Metastatic or Recurrent HPV-Related Cervical Carcinoma of Either Squamous Cell or Adenocarcinoma Histologies

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety of ipilimumab in eligible patients with recurrent or metastatic cervical cancer.

II. To assess the antitumor activity of ipilimumab in eligible patients with recurrent or metastatic cervical cancer via assessment of objective response rates (ORR).

SECONDARY OBJECTIVES:

  1. To assess the antitumor activity of ipilimumab through secondary endpoints including of disease stabilization and progression free survival (PFS).

II. Assessment of antitumor activity of ipilimumab using immune-related response criteria (irRC) III. Assessment of the predictive value of baseline C-reactive protein. IV. Assess the biologic responses of exposure to ipilimumab via correlative studies involving analysis of lymphocyte subsets and assessment of cervical cancer-antigen specific T cells anti-tumor response.

  1. Evaluation of archival tissue with regard to markers of immune population in correlation with clinical stage and response to treatment.

OUTLINE:

Patients receive ipilimumab intravenously (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.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Being tested
Ipilimumab, Laboratory Biomarker Analysis
Medical subject headings
Papillomavirus Infections, Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01693783
Study groupRoleWhat they receive
Treatment (ipilimumab)ExperimentalPatients 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.
Receives: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 1 year

  2. 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.

    Measured: Up to 1 year

Secondary outcomes (6)
  1. Antitumor Activity (Partial Response, Complete Response, and Stable Disease) Using Immune-related Response Criteria (irRC)

    Immune-Related Complete Response (irCR): complete disappearance of all lesions for at least 4 weeks from the date of documentation of complete response. Immune-Related Partial Response (irPR): The sum of the products of the two largest perpendicular diameters of all index lesions is measured and captured as the SPD baseline. At each subsequent tumor assessment, the sum of the products of the two largest perpendicular diameters of all index lesions and of new measurable lesions are added together to provide the Immune Response Sum of Product Diameters (irSPD). A decrease, relative to baseline of the irSPD compared to the previous SPD baseline, of 50% or greater is considered an immune Partial Response (irPR). irStable Disease (irSD): does not meet criteria for irCR or irPR, in the absence of progressive disease.

    Measured: Up to 1 year

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

    Number of Participants with Cervical Cancer-antigen Specific T Cells Anti-tumor Response

    Measured: Up to 1 year

  3. Disease Stabilization

    As per RECIST v1.1, stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: Up to 1 year

  4. Markers of Immune Population, Evaluated in Archival Tissue

    Evaluation of archival tissue with regard to markers of immune population in correlation with clinical stage and response to treatment

    Measured: Baseline to 1 year after treatment

  5. Predictive Value of Baseline C-reactive Protein

    Measured: Up to week 3 of course 4

  6. Progression Free Survival

    Progressive disease (PD), as per RECIST v1.1, is defined as at least a 20% increase in the sum of the diameters of target lesions and an absolute increase of at least 5mm, or the appearance of one or more new lesions. Computed using the Kaplan-Meier method.

    Measured: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2012 (estimated)
  2. Study start3 Dec 2012
  3. Primary completion18 Mar 2021
  4. Study completion24 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01693783
Sponsor's protocol ID
NCI-2012-02877
Other IDs
NCI-2012-02877, PHL-085, PHL-085, 9209, N01CM00032, N01CM00038, N01CM00071, U10CA180821
Status last verified
Oct 2022
First submitted
21 Sep 2012
Last updated
8 Nov 2022
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab and Laboratory Biomarker Analysis in people with Cervical Adenocarcinoma and Cervical Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 13 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 (time frame: Up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.

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