Know Cancer

forgot password

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

Phase 2
18 Years
Open (Enrolling)
Cervical Cancer, Human Papillomavirus, Adenocarcinoma

Thank you

Trial Information

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

This study will have two parts: a phase 1 run-in which will assess the safety of ipilimumab
in the study population and a phase 2 part which will further assess the safety and
effectiveness of the drug.

During the study, research blood and tumor samples will be taken to test for immune
biomarkers (substances which may be a sign that participants are developing antibodies
towards the drug which may potentially affect the effectiveness of the drug) and other
biomarkers (other important substances in the body that may be indicators cancer or of
response to the study drug) to better understand the study drug.

Inclusion Criteria:

- Histologically or cytologically confirmed metastatic or recurrent HPV-related
cervical cancer of squamous, adenocarcinoma or mixed histology type not suited to
definitive localized therapy.

- 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 ≥20 mm with conventional techniques or as ≥10 mm
with spiral CT scan, MRI, or calipers by clinical exam.

- Previous Therapy:

- May have undergone surgery and/or received definitive radiation or
chemo-radiation for localized disease in the past.

- Radiation treatment must have been completed ≥ 3 months prior to enrollment.

- Must have been exposed to platinum chemotherapy either as part of definitive
chemo-radiation OR as first line systemic treatment for metastatic disease.

- 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.

- Age ≥18 years. Because no dosing or adverse event data are currently available on the
use of Ipilimumab in patients <18 years of age, children are excluded from this

- ECOG performance status 0-1

- Life expectancy of greater than 3 months

- Must have normal organ and marrow function as defined below:

- 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

- TSH within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal

- creatinine <1.25 ULN OR creatinine clearance ≥50mL/min/1.73 m^2 as calculated
by the Cockroft and Gault formula

- All radiology studies must be performed ≤ 3 weeks prior to the start of therap

- Treated and asymptomatic brain metastases are eligible. Patients that received
palliative radiation (for brain metastases) are eligible if they do not require
maintenance steroid treatment, have been asymptomatic for at least 2 weeks following
cessation of 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).

- Willing to undergo tumour biopsy pre-treatment (7 days prior to registration) and
post-treatment (within the first week of cycle 2 onset). Patients who consent but
have tumour 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 PI prior to registration continuation of treatment.

Exclusion Criteria:

- Had chemotherapy < 4 weeks prior to enrollment (<6 weeks for nitrosoureas or
mitomycin C) or who had radiation < 3months prior to enrollment or those who have not
recovered (≤ grade 1) from adverse events related to previous treatments are

- History of prior treatment with Ipilimumab or other CTLA4 agonists or antagonists,
anti-PD 1 antibody, CD137 agonist or other immune activating therapy such as anti-CD
40 antibody are excluded.

- 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]); CNS or motor neuropathy considered of
autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis, multiple

- 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.

- 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

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Ipilimumab.

- Patients requiring systemic steroids are excluded, as these drugs may interfere with
the activity of Ipilimumab if administered at the time of the first Ipilimumab dose.

- Narcotics should be used with caution as they may mask the signs and symptoms of
serious gastrointestinal irAEs including intestinal perforation.

- 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.

- Chronic Hepatitis B or hepatitis C infections should be excluded because of potential
effects on immune function and/ or drug interactions.

- Pregnant women are excluded from this study because Ipilimumab is an agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with Ipilimumab, breastfeeding should be discontinued if the mother is treated
with Ipilimumab.

- Active or chronic infection with HIV who have raised viral loads or uncontrolled
disease are ineligible because of the potential for anticipated and unknown adverse
immune related effects secondary to treatment with Ipilimumab. 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with adverse events

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Amit Oza, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Cancer Centre


Canada: Ethics Review Committee

Study ID:

PHL-085/NCI 9209



Start Date:

December 2012

Completion Date:

June 2015

Related Keywords:

  • Cervical Cancer
  • Human Papillomavirus
  • Adenocarcinoma
  • Ipilimumab
  • MDX-010
  • BMS-734016
  • Monoclonal antibody
  • Cervical cancer
  • Human papillomavirus
  • HPV
  • Squamous cell
  • Adenocarcinoma
  • Metastatic
  • Recurrent
  • First line
  • Second line
  • Third line
  • Biopsy
  • Tumor tissue
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Uterine Cervical Neoplasms