NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphodepleting Regimen in Metastatic Cancers Plus the Administration of Pembrolizumab

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 Years
Max Age: 72 Years

Referral Letter Required

No

Population Exclusion(s)

Children;
Pregnant Women;
Fetuses

Keywords

Digestive Tract Cancers;
Breast Cancer;
Endocrine Tumors;
Ovarian/Endometrial Cancer;
Genitourinary Cancer

Recruitment Keyword(s)

None

Condition(s)

Metastatic colorectal cancer;
Metastatic pancreatic cancer;
Metastatic Ovarian Cancer;
Metastatic Breast Carcinoma;
Metastatic endocrine tumors/ neuroendocrine tumors

Investigational Drug(s)

Young TIL
Aldesleukin

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: Young TIL
Drug: Aldesleukin
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Pembrolizumab (Keytruda)

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 upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial cancer, or glioblastoma refractory to standard chemotherapy.

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.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

-Measurable (per RECIST v1.0 criteria), metastatic cancer of one of the following types: upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial, or endocrine tumors including neuroendocrine tumors. Patients must have 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.

-Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology.

-Refractory to approved standard systemic therapy. Specifically:

--Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan.

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

--Patients with breast and ovarian cancer must be refractory to both first and second line treatments and must have received at least one second-line chemotherapy regimen.

--Patients with glioblastoma must have received standard surgery, radiation therapy, and chemotherapy for their primary tumors and require resection of their tumors for palliative or other clinical indications. These patients will not undergo surgery solely for treatment on this protocol.

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

- Age greater than or equal to 18 years and less than or equal to 72 years.

-Clinical performance status of ECOG 0 or 1.

-Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.

-Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.

Serology

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

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

Hematology

-ANC > 1000/mm3 without the support of filgrastim

-WBC greater than or equal to 2500/mm3

-Platelet count greater than or equal to 80,000/mm3

-Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.

Chemistry

-Serum ALT/AST less than or equal to 5.0 x ULN

-Serum creatinine less than or equal to 1.6 mg/dL

-Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL.

-Patients must have completed any prior systemic therapy at the time of enrollment.

Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related organ toxicities have recovered to grade 1 or less.

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

-Willing to sign a durable power of attorney.

-Subjects must be co-enrolled on protocol 03-C-0277.

Exclusion Criteria:

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

-Concurrent systemic steroid therapy, except for patients with recurrent glioblastoma who require steroids for clinical indications.

-Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

-Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion.

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

-History of major organ autoimmune disease.

-Grade 3 or 4 major organ irAEs clinically attributed to anti-PD-1/PD-L1 therapy.

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

to its toxicities.)

-History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.

-History of coronary revascularization or ischemic symptoms.

-For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.

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

-For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.

-Patients who are receiving any other investigational agents.


--Back to Top--

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.

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)



NCI/Surgery Branch Recruitment Center
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 2-1730
10 Center Drive
Bethesda, Maryland 20892
(866) 820-4505
IRC@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

--Back to Top--

NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphodepleting Regimen in Metastatic Cancers Plus the Administration of Pembrolizumab

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 Years
Max Age: 72 Years

Referral Letter Required

No

Population Exclusion(s)

Children;
Pregnant Women;
Fetuses

Keywords

Digestive Tract Cancers;
Breast Cancer;
Endocrine Tumors;
Ovarian/Endometrial Cancer;
Genitourinary Cancer

Recruitment Keyword(s)

None

Condition(s)

Metastatic colorectal cancer;
Metastatic pancreatic cancer;
Metastatic Ovarian Cancer;
Metastatic Breast Carcinoma;
Metastatic endocrine tumors/ neuroendocrine tumors

Investigational Drug(s)

Young TIL
Aldesleukin

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: Young TIL
Drug: Aldesleukin
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Pembrolizumab (Keytruda)

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 upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial cancer, or glioblastoma refractory to standard chemotherapy.

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.

--Back to Top--

Eligibility

INCLUSION CRITERIA:

-Measurable (per RECIST v1.0 criteria), metastatic cancer of one of the following types: upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial, or endocrine tumors including neuroendocrine tumors. Patients must have 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.

-Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology.

-Refractory to approved standard systemic therapy. Specifically:

--Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan.

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

--Patients with breast and ovarian cancer must be refractory to both first and second line treatments and must have received at least one second-line chemotherapy regimen.

--Patients with glioblastoma must have received standard surgery, radiation therapy, and chemotherapy for their primary tumors and require resection of their tumors for palliative or other clinical indications. These patients will not undergo surgery solely for treatment on this protocol.

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

- Age greater than or equal to 18 years and less than or equal to 72 years.

-Clinical performance status of ECOG 0 or 1.

-Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.

-Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.

Serology

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

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

Hematology

-ANC > 1000/mm3 without the support of filgrastim

-WBC greater than or equal to 2500/mm3

-Platelet count greater than or equal to 80,000/mm3

-Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.

Chemistry

-Serum ALT/AST less than or equal to 5.0 x ULN

-Serum creatinine less than or equal to 1.6 mg/dL

-Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL.

-Patients must have completed any prior systemic therapy at the time of enrollment.

Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related organ toxicities have recovered to grade 1 or less.

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

-Willing to sign a durable power of attorney.

-Subjects must be co-enrolled on protocol 03-C-0277.

Exclusion Criteria:

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

-Concurrent systemic steroid therapy, except for patients with recurrent glioblastoma who require steroids for clinical indications.

-Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

-Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion.

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

-History of major organ autoimmune disease.

-Grade 3 or 4 major organ irAEs clinically attributed to anti-PD-1/PD-L1 therapy.

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

to its toxicities.)

-History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.

-History of coronary revascularization or ischemic symptoms.

-For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.

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

-For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.

-Patients who are receiving any other investigational agents.


--Back to Top--

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.

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)



NCI/Surgery Branch Recruitment Center
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 2-1730
10 Center Drive
Bethesda, Maryland 20892
(866) 820-4505
IRC@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

--Back to Top--