Recruiting
Phase 2

Immunotherapy

Sponsor:

National Cancer Institute (NCI)

Code:

NCT01174121

Conditions

Metastatic Colorectal Cancer

Metastatic Pancreatic Cancer

Metastatic Ovarian Cancer

Metastatic Breast Carcinoma

Metastatic Endocrine Tumors/ Neuroendocrine Tumors

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab (Keytruda)

Fludarabine

Cyclophosphamide

Aldesleukin

Young TIL

Study Details

Brief summary:

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 18-72 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.

...

Conditions

Metastatic Colorectal Cancer

Metastatic Pancreatic Cancer

Metastatic Ovarian Cancer

Metastatic Breast Carcinoma

Metastatic Endocrine Tumors/ Neuroendocrine Tumors

Study ID

NCT01174121

Start date

Aug 26, 2010

Status verified date

Aug 17, 2026

Completion date

Dec 27, 2029

Anticipated

Primary completion date

Dec 27, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • 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 must have received sorafenib (Nexavar(R)), 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 3 or fewer brain metastases that are < 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. Patients with surgically resected brain metastases are 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 sexes must be willing to practice birth control from the time of enrollment on this study and 12 months after the last dose of combined chemotherapy for individuals of child-bearing potential (IOCBP) and for four months after treatment for individuals that can father children.
  • IOCBP must have a negative pregnancy test be 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/mm\^3 without the support of filgrastim
  • WBC greater than or equal to 2500/mm\^3
  • Platelet count greater than or equal to 80,000/mm\^3
  • 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 1.5 x ULN
  • 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 major organ toxicities have recovered to less than or equal to grade 1.

  • 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:

  • Participants who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
  • Concurrent systemic steroid therapy.
  • 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.

Study Design

Enrollment

332 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1/CD8+ Enriched TIL (CLOSED)

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young CD8+ enriched TIL + high-dose aldesleukin (CLOSED)

experimental: 2/Unselected TIL (CLOSED)

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin (CLOSED)

experimental: 3/Unselected TIL + Pembro Prior to Cells

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin + pembrolizumab prior to cell administration and 3 additional doses every 3 weeks following cell infusion

experimental: 4/Unselected TIL + Pembro at POD

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin + pembrolizumab within 4 weeks of progressive disease for up to 8 doses every 3 weeks

experimental: 5/Unselected TIL + Pembro Prior to Cells

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young unselected TIL + high-dose aldesleukin + pembrolizumab prior to cell administration and 3 additional doses every 3 weeks following cell infusion

Interventions

Pembrolizumab (Keytruda)

Arm 3 or 5: Pembrolizumab 2mg/kg IV over approximately 30 minutes on Days -2, 21, 42, and 63 Arm 4: Pembrolizumab 2mg/kg IV over approximately 30 minutes (for patients who meet progressive disease per RECIST criteria and have resolved major toxicities after cell infusion or anytime during the post-treatment

evaluation period; starting within 4 weeks of progression; may receive up to 8 doses every 3 weeks).

Fludarabine

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Cyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with Mesna 15 mg/kg/day X2 days over 1 hr.

Aldesleukin

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses.)

Young TIL

Day 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes (one to four days after the last dose of fludarabine).

Primary outcome measure

  • Response rate [ Time Frame: 6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2 years, then per PI discretion ]

Central Contacts and Locations

Central contacts

NCI/Surgery Branch Recruitment Center

(866) 820-4505IRC@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 1, 2026

Last verified

Aug 17, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-01.