Overview

Study of the Drug Ipilimumab for Metastatic Merkel Cell Carcinoma

Status:
Withdrawn
Trial end date:
2014-02-03
Target enrollment:
0
Participant gender:
All
Summary
Background: - Ipilimumab is a drug used to treat melanoma that cannot be treated surgically. It targets a molecule found on T-cells in the human immune system. Blocking these molecules on the T-cells might allow the cells to help destroy melanoma cells more effectively. This drug has also been studied in other cancers such as prostate cancer and lung cancer, but not yet in Merkel cell carcinoma (MCC). Researchers think therapy like ipilimumab that enhances the immune system may be effective against MCC. They want to study how safe the drug is and its effect on the immune system and tumors. Objectives: - To determine the number of subjects with MCC who take the study drug that remain alive 12 months later. Eligibility: - Adults 18 years and older who have metastatic MCC. Design: - Participants will be screened with a medical history and physical exam. - Participants will receive the study drug 4 times, one dose every 21 days. After the 4 visits, participants will receive a maintenance dose of the drug every 12 weeks until the drug is no longer beneficial. - They will receive the drug through a plastic tube usually inserted in a vein on the arm. - It will take 90 minutes to give each dose. - At all visits, participants will be screened with a medical history, physical exam, and blood tests. Any tumors on their skin will be measured and photographed. - Every 12 weeks during the study and maintenance period, participants will have a CT scan. Throughout the study and maintenance period, they will have blood and skin tests.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Antibodies, Monoclonal
Ipilimumab
Criteria
- INCLUSION CRITERIA:

- Diagnosis of Merkel cell carcinoma confirmed by the Laboratory of Pathology, NCI, or
the participating institute s Department of Pathology.

- Unresectable or metastatic Merkel cell carcinoma

- Measurable disease as defined by lesions that are measured in at least one dimension
>20mm by CXR, as > 10mm with CT scans, or > 10mm with calibers by clinical exam.

- Life expectancy greater than or equal to 6 months.

- ECOG performance status of 0-2

- Willing to travel to the NIH or study sub-sites (MSKCC, UMich, or Penn) for follow-up
visits.

- Patients must have recovered from acute toxicities related to prior therapy or
surgery.

- Patients must receive at least one line of chemotherapy and achieve partial
response(30% reduction in tumor burden) or better prior to enrollment. EXCEPTION:
Patients with asymptomatic tumors showing no or minimal progression (<20% tumor
burden) within the last 2 months can be enrolled without prior chemotherapy.

- Age greater than equal 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 study, but may be eligible for future pediatric trials.

- Patients must have adequate hematological, hepatic, and renal laboratory values, as
defined below:

- leukocytes >3,000/mcL

- absolute neutrophil count >1,500/mcL

- platelets >100,000/mcL

-----total bilirubin within normal institutional limits (except subjects with
Gilbert s Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

- AST(SGOT)/ALT(SGPT) <2.5 times institutional upper limit of normal

- creatinine <2.0 times institutional upper limit of normal.

- The effects of ipilimumab on the developing human fetus are unknown. For this reason
and because ipilimumab was found to have teratogenic and abortifacient effects in
animal studies, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry, for the duration of study participation, and for 4 months after the last
injection of ipilimumab. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately.

- Ability of subject to understand and the willingness to sign a written informed
consent document.

EXCLUSION CRITERIA:

Prior treatment with ipilimumab.

-Patients who are immunocompromised as listed:

- Human immunodeficiency virus infection, or Hepatitis B or C infection, due to the
unknown effects of ipilimumab on viral replication and immune function and the
potential for severe side effects.

- Chronic administration (defined as daily or every other day for continued use >14
days) of systemic corticosteroids (including steroid eye drops) or other immune
suppressive drugs, within 14 days of the first planned dose of ipilimumab. Nasal, or
inhaled steroid, and topical steroid creams for small body areas are not excluded.

- Patients who have undergone allogeneic peripheral stem cell transplantation, or solid
organ transplantation requiring immunosuppression

Prior Splenectomy

-Patients with history of, or active autoimmune disease that has required treatment, such
as Addison's disease, autoimmune thyroiditis, Grave s disease, systemic lupus erythematous,
rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants),
autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barr(SqrRoot)(Copyright)
syndrome), Goodpasture syndrome, ulcerative or hemorrhagic colitis, autoimmune
hypophysitis/hypopituitarism, and autoimmune hemolytic anemia.

EXCEPTIONS: Patients with a history of autoimmunity that has not required systemic
immunosuppressive therapy or does not threaten vital organ function including CNS, heart,
lungs, kidneys, skin, and GI tract will not be excluded. Patients with type 1 diabetes
mellitus, or vitiligo, or endocrine deficiencies such as hypothyroidism will not be
excluded if the condition is well controlled.

- Other active malignancies within the past 12 months. EXCEPTIONS: Patients with
adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma
of the cervix or bladder will not be excluded. Patients with low or intermediate-risk
CLL (Rai stage 0-II, Binet stage A or B) without progressive or symptomatic disease,
who are being monitored without therapy will not be excluded.

- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
accident/stroke < 6 months prior to enrollment, myocardial infarction < 6 months prior
to enrollment, unstable angina, or congestive heart failure ( (Bullet) NYHA III).

- Pulmonary disease which, in the opinion of the investigator, may impair the patient's
respiratory tolerance to the study drug (e.g., interstitial lung disease, severe
chronic obstructive pulmonary disease).

- Presence of serious or life-threatening intercurrent medical illness.

- Patients with symptomatic or progressive (progression within the last 3 months) brain
metastases are excluded from this clinical trial because of their poor prognosis and
because they often develop progressive neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events.

- Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI
obstruction and abdominal carcinomatosis which are known risk factors for bowel
perforation.

- Pregnant women are excluded from this study because, based on animal studies,
ipilimumab has 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.

- Any condition which, in the opinion of the investigator, would prevent full
participation in this trial (including the long-term follow-up), or would interfere
with the evaluation of the trial endpoints.

- Receipt of chemotherapy or an investigational agent within 21 days (or 60 days for an
antibody-based therapy) of the first planned dose of study drugs.