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Cervical AdenocarcinomaPhase 1NCT01711515

Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

A Phase 1 study testing Cisplatin, External Beam Radiation Therapy and Internal Radiation Therapy in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 16 sites in United States.

Completed

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

Official record
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Trial summary

This phase I trial studies the side effects and best dose of ipilimumab when given after chemoradiation therapy in treating patients with stages IB2-IIB or IIIB-IVA cervical cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Cisplatin, External Beam Radiation Therapy and Internal Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
16 sitesUnited States
Study dates
1 Oct 2012to 17 Jul 2020
Phase
Phase 1
Are there results?
None posted in the registry

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 with histologically confirmed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): International Federation of Gynecology and Obstetrics (FIGO) clinical stages IB2/IIA with positive para-aortic lymph nodes or FIGO clinical stages IIB/IIIB/IVA with positive pelvic and/or para-aortic lymph nodes; nodal status will be confirmed by PET/CT scan, fine needle biopsy, extra peritoneal biopsy, laparoscopic biopsy or lymphadenectomy
  • Patients must have a Gynecologic Oncology Group (GOG) performance status of 0-1
  • Absolute neutrophil count (ANC) >= 1,500/mcl
  • Platelets >= 100,000/mcl
  • Creatinine =< institutional upper limit normal (ULN); note: if creatinine > ULN, creatinine clearance must be > 50 mL/min
  • Bilirubin =< 1.5 x ULN
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  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Neuropathy (sensory and motor) =< grade 1
  • Patients with ureteral obstruction (i.e., hydronephrosis identified on CT imaging) must undergo stent or nephrostomy tube placement prior to study entry
  • Patients must meet the pre-entry requirements specified
  • Patients must have signed an approved informed consent and authorization permitting the release of personal health information
  • Patients of child-bearing potential must have a negative serum pregnancy test prior to study entry (within 72 hours prior to initiation of study treatment) and be practicing an effective form of contraception; women should not breast-feed while on this study
  • Patients must not be receiving any other investigational agent
  • Patients should have an audiogram at baseline, and patients with pre-existing hearing loss or hearing loss during treatment should be assessed frequently during cisplatin therapy

Who cannot join

  • Patients who have received previous pelvic or abdominal radiation, cytotoxic chemotherapy, or previous therapy of any kind for this malignancy or any pelvic or abdominal radiation for any prior malignancy
  • Patients with active infection
  • Patients who have circumstances that will not permit completion of this study or the required follow-up
  • Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment prevents full delivery of this protocol therapy
  • Patients who have undergone major surgery, excluding diagnostic biopsy, within 30 days (to allow for full recovery) prior to registration
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  • Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias within 6 months of registration
  • Patients with a history of prior treatment with ipilimumab, anti-programmed cell death (PD) 1 antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody
  • 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 with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) antibody
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition ipilimumab or other agents used in study
  • Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • The Hospital of Central Connecticut

    New Britain, Connecticut, 06050

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Health/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

Other trials in United States

About this study

Official title: A Phase I Trial of Sequential Ipilimumab After Chemoradiation for the Primary Treatment of Patients With Locally Advanced Cervical Cancer Stages IB2/IIA With Positive Para-Aortic Lymph Nodes Only and Stage IIB/IIIB/IVA With Positive Lymph Nodes

This phase I trial studies the side effects and best dose of ipilimumab when given after chemoradiation therapy in treating patients with stages IB2-IIB or IIIB-IVA cervical cancer. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as ipilimumab, may find tumor cells and help carry tumor-killing substances to them. Giving ipilimumab together with chemoradiation therapy may be a better way treat cervical cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of adjuvant ipilimumab following concurrent weekly cisplatin and extended field radiation in women with newly diagnosed locally advanced cervical cancer stage IB2/ IIA with-positive para-aortic lymph nodes only and stage IIB/IIIB/IVA with positive lymph nodes.

II. To determine the feasibility of the treatment regimen over the four cycles of adjuvant ipilimumab once the MTD is estimated.

III. To assess the toxicities of the treatment regimen per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

SECONDARY OBJECTIVES:

  1. To examine progression free survival for 1 year after study completion. II. To determine site of recurrence, loco-regional versus distant, for one year after completion of therapy.

III. To estimate the frequency of chronic toxicities experienced within one year after completion of therapy.

TERTIARY OBJECTIVES:

  1. To enumerate the human papillomavirus (HPV)-subtype-specific T-cells and characterize the kinetics of HPV-subtype-specific T-cell expansion associated with chemoradiation and ipilimumab treatment.

II. To characterize the association between differential expression of immune markers on leukocytes from human leukocyte antigen (HLA)-A*0201 patients and response to chemoradiation and ipilimumab treatment.

III. To assess qualitative changes in maximum standardized uptake value (SUVmax) from positron emission tomography (PET)/computed tomography (CT) after treatment with chemoradiation and ipilimumab.

IV. To bank residual plasma (obtained from leukocyte processing) for future research.

OUTLINE: This is a dose-escalation study of ipilimumab.

Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo external beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 1 year.

Being tested
Cisplatin, External Beam Radiation Therapy, Internal Radiation Therapy, Ipilimumab, Laboratory Biomarker Analysis
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

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

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo external beam radiation therapy

  • Internal Radiation TherapyRadiation

    Also called Brachytherapy, Brachytherapy, NOS, Internal Radiation, Internal Radiation Brachytherapy

    Undergo intracavitary brachytherapy

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01711515
Study groupRoleWhat they receive
Treatment (cisplatin, radiation therapy, and ipilimumab)ExperimentalPatients receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, and 36, undergo extended beam radiation therapy 5 days a week for 6 weeks, and then undergo intracavitary brachytherapy for approximately 2 weeks. Within 2 weeks, patients receive ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks.
Receives: Drug: Cisplatin; Radiation: External Beam Radiation Therapy; Radiation: Internal Radiation Therapy; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. DLTs occurring during adjuvant ipilimumab in the dose escalation phase

    Measured: During first 2 courses of treatment

  2. DLTs occurring in the feasibility phase

    Measured: Over 4 courses of treatment

  3. Toxicities as assessed by CTCAE version 4

    Measured: Up to 2 years post-treatment

Secondary outcomes (5)

  1. Response rate in patients enrolled with measurable disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    Relationships of translational research endpoints to response will be explored if practical.

    Measured: Up to 2 years post-treatment

  2. Progression-free survival (PFS)

    Will be summarized using Kaplan-Meier plots. Relationships of translational research endpoints to PFS will be explored if practical.

    Measured: From time of study entry to time of progression or death, whichever occurs first, assessed up to 1 year post-treatment

  3. Overall survival

    Will be summarized using Kaplan-Meier plots.

    Measured: From time of study entry to time of death or the date the patient was last confirmed to be alive, assessed up to 1 year post-treatment

  4. Location of recurrence (loco-regional versus distant)

    Measured: Up to 1 year post-treatment

  5. Chronic toxicities experienced within one year of completion of therapy

    Measured: Up to 1 year post-treatment

Timeline

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

  1. First posted22 Oct 2012 (estimated)
  2. Study start1 Oct 2012
  3. Primary completion9 Feb 2017
  4. Study completion17 Jul 2020

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01711515
Sponsor's protocol ID
NCI-2012-01733
Other IDs
NCI-2012-01733, GOG-PIS1102, GOG-9929, GOG-9929, GOG-9929, U10CA180830, U10CA180868, U10CA027469
Status last verified
Aug 2020
First submitted
18 Oct 2012
Last updated
2 Sep 2020
Results posted
No
Data monitoring committee
No

Publications

  • Da Silva DM, Enserro DM, Mayadev JS, Skeate JG, Matsuo K, Pham HQ, Lankes HA, Moxley KM, Ghamande SA, Lin YG, Schilder RJ, Birrer MJ, Kast WM. Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929). Clin Cancer Res. 2020 Nov 1;26(21):5621-5630. doi: 10.1158/1078-0432.CCR-20-0776. Epub 2020 Aug 18.

    PubMed 32816895

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cisplatin, External Beam Radiation Therapy and Internal Radiation Therapy in people with Cervical Adenocarcinoma and Cervical Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 16 sites in United States.

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 15 inclusion and 13 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 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

DLTs occurring during adjuvant ipilimumab in the dose escalation phase (time frame: During first 2 courses of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01711515, which also lists 1 linked publication.

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 2 Sep 2020.

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