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Protocol Details

A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Cancers Plus the Administration of Pembrolizumabat Time of Progression

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

10-C-0166

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 70

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Digestive Tract Cancers;
Breast Cancer;
Cell Therapy;
Ovarian/Endometrial Cancer;
Urothelial Cancers

Recruitment Keyword(s)

None

Condition(s)

Metastatic colorectal cancer;
Metastatic gastric cancer;
Metastatic pancreatic cancer;
Metastatic hepatocellular carcinoma;
Metastatic cholangiocarcinoma

Investigational Drug(s)

Young TIL

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: Young TIL
Drug: Aldesleukin
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Pembrolizumab

Supporting Site

National Cancer Institute

Background:

The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people with digestive tract, urothelial, breast, or ovarian/endometrial cancers. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells.

Objective:

The purpose of this study is to see if these specifically selected tumor fighting cells can cause digestive tract, urothelial, breast, or ovarian/endometrial tumors to shrink and to see if this treatment is safe.

Eligibility:

- Adults age 18-70 with metastatic digestive tract, urothelial, breast, or ovarian/endometrial cancer who have a tumor that can be safely removed.

Design:

Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed.

Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product.

Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}

Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.

Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

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Eligibility

INCLUSION CRITERIA:

a. Measurable metastatic (stage IV) gastric, gastroesophageal, pancreatic, hepatocellular carcinoma, cholangiocarcinoma, gallbladder, colorectal, urothelial, breast, and ovarian/endometrial carcinomas with at least one lesion that is resectable for TIL generation with minimal morbidity preferentially using minimal invasive laparoscopic or thoracoscopic surgery for removal of superficial tumor deposit, plus one other lesion that can be measured.

b. All patients must be refractory to approved standard systemic therapy.

Specifically :

- Metastatic colorectal patients must have received oxaliplatin or irinotecan.

- Hepatocellular carcinoma patients must have received sorafenib (Nexavar ), since level 1 data support a survival benefit with this agent.

- Breast and Ovarian cancer patients must be refractory to both 1st line and 2nd line treatments and must have received at least one second line chemotherapy regimen.

c.Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible.

d. Clinical performance status of ECOG 0 or 1.

e. Greater than or equal to 18 years of age and less than or equal to 70 years of age.

f. Willing to practice birth control during treatment and for four months after receiving the treatment.

g. Willing to sign a durable power of attorney.

h. Able to understand and sign the Informed Consent Document.

i. Hematology:

- Absolute neutrophil count greater than 1000/mm(3) without support of filgrastim.

- Normal WBC (> 3000/mm(3)).

- Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this cut-off.

- Platelet count greater than 100,000/mm(3).

- Normal prothrombin time (less than or equal to 15.2 seconds).

j. Serology:

- Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus may be less responsive to the experimental treatment and more susceptible to its toxicities.)

- Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

k. Chemistry:

- Serum ALT/AST less than five times the upper limit of normal.

- Serum creatinine less than or equal to 1.6 mg/dl.

- Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome, who must have a total bilirubin less than or equal to 3 mg/dl.

l. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.

m. Four weeks must have elapsed since any prior antibody therapies to allow antibody levels to decline.

n. Subjects must be co-enrolled in protocol 03-C-0277.

EXCLUSION CRITERIA:

a. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

b. Concurrent systemic steroid therapy.

c. Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses

d. Advanced primary with impeding occlusion, perforation or bleeding, dependant on transfusion.

e. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).

f. History of major organ autoimmune disease.

g. Grade 3 or 4 major organ Immune-Related Adverse Events (IRAEs) following treatment with anti-PD-1/PD-L1

h. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)

i. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

j. History of coronary revascularization or ischemic symptoms.

k. Any patient known to have an LVEF less than or equal to 45%.

l. Documented LVEF of less than or equal to 45% tested in patients with:

- Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block

- Age greater than or equal to 60 years old

m. Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction.

n. Documented FEV1 less than or equal to 60% predicted tested in patients with:

-A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).

- Symptoms of respiratory dysfunction

o. Patients who are receiving any other investigational agents.


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Citations:

Chiba T, Ohtani H, Mizoi T, Naito Y, Sato E, Nagura H, Ohuchi A, Ohuchi K, Shiiba K, Kurokawa Y, Satomi S. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer. 2004 Nov 1;91(9):1711-7.

Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999 Sep;230(3):309-18.

Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D'Angelica M. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007 Oct 10;25(29):4575-80.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)
BG 10-CRC RM 3-3940
10 CENTER DR
BETHESDA MD 20814
(866) 820-4505
sar@mail.nih.gov

Colleen E. Buckley, R.N.
National Cancer Institute (NCI)
BG 10-CRC RM 2-1730
10 CENTER DR
BETHESDA MD 20814
(866) 820-4505
ncisbirc@mail.nih.gov

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505
ncisbirc@mail.nih.gov

Clinical Trials Number:

NCT01174121

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