Clinical Trials Logo

Clinical Trial Summary


In gene transfer therapy, cells are taken from a person s tumor to isolate mutations. White blood cells are then taken from the person's body, changed with a type of virus to attack the tumor cells, and returned to the person.


To see if gene transfer therapy shrinks tumors.


People with certain metastatic cancer for which standard treatments have not worked


Participants will complete screening and stages 1-3 under another protocol. Screening includes:

Undergoing a biopsy or surgery at the NIH to obtain pieces of tumor in order to grow tumor cells

Medical history

Physical exam


Blood, urine, heart, and lung tests

The study has 7 stages:

1. Screening tests repeated over 1-2 weeks. Participants will have leukapheresis: Blood is removed by a needle in one arm. A machine removes white blood cells. The rest of the blood is returned by a needle in the other arm. An IV catheter will be placed in the chest.

2. Care at home over 6-12 weeks.

3. Stopping therapy for 4-6 weeks while their cells are changed in a lab.

4. Hospital stay for 1 week to get chemotherapy by IV.

5. Receiving changed cells by catheter. Then getting a drug over 1-5 days to help the cells live longer.

6. Recover in the hospital for 1 2 weeks. Participants will get drugs and have blood and urine tests.

7. Participants will take an antibiotic and maybe an antiviral for at least 6 months after treatment. They will have repeat screening tests at visits every few months for the first year, every 6 months for the second year, then as determined.

Clinical Trial Description


- The administration of autologous tumor-infiltrating lymphocytes (TIL) can mediate complete, durable regressions in 20-25% of patients with metastatic melanoma. Recent studies have shown that these TIL predominantly recognize unique mutated neoantigens expressed by the cancer not shared by other melanomas.

- Administration of bulk autologous TIL to patients with a variety of other solid cancers, including cancers of the gastrointestinal tract and genitourinary tract, have little if any therapeutic impact.

- Recent studies in the National Cancer Institute Surgery Branch, (NCI-SB), have shown that TIL from non-melanoma solid cancers can also contain T-cells reactive against non-shared unique mutated neoantigens expressed in the cancer. The frequency of these T-cells is very low (often < 0.1%) and it is thus difficult to isolate and grow mutation reactive T-cells to levels required for effective therapy.

- In a single patient with chemo-refractory metastatic cholangiocarcinoma we were able to grow a relatively pure population of neoantigen reactive TIL and administration of these cells mediated a near-complete regression of all metastatic disease now lasting 2.5 years.

- We have developed approaches to identify these rare neoantigen reactive T-cells from common non-melanoma cancers, to isolate their T-cell receptors (TCR), and to genetically engineer autologous peripheral blood lymphocytes (PBL) to express these TCRs with high efficiency. The neoantigen TCR gene-modified cells can recognize and destroy the autologous cancer in vitro.

- We are now proposing a clinical protocol to treat patients with refractory solid cancers using the adoptive transfer of autologous PBL transduced with genes encoding TCRs that recognize unique mutated neoantigens expressed by the cancer.


-Primary objective:

--Determine the rate of objective response (using RECIST v1.1 criteria) of patients with solid cancers who receive autologous PBL that have been transduced with genes encoding T-cell receptors that recognize mutated neoantigens in the autologous cancer.


-Patients must be/have:

- Age greater than or equal to 18 years and less than or equal to 70 years

- Measurable solid cancer with at least one lesion that is resectable for TIL generation with minimal morbidity plus at least one other lesion that can be measured, that falls into one of four cohorts: (1) gastrointestinal and genitourinary cancers; (2) breast, ovarian, and other solid cancers; (3) non-small cell lung cancer (NSCLC); and, (4) glioblastoma. Metastatic disease is required for cohorts 1-3, but not for cohort 4.

- Evaluable solid cancer that has recurred following standard chemotherapy or standard systemic therapy

- Normal basic laboratory values.

- At least one lesion suitable for surgical resection for the preparation of the cell product

- No allergies or hypersensitivity to high-dose aldesleukin administration

- No concurrent major medical illnesses or any form of immunodeficiency.


- Patients will undergo resection or biopsy to obtain tumor for generation of autologous TIL cultures. This will be conducted under the NCI-SB cell harvest protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols).

- Patients will be entered into four cohorts: (1) gastrointestinal and genitourinary cancers, (2) breast, ovarian, and other solid cancers; (3) non-small cell lung cancer (NSCLC); and, (4) glioblastoma. Exomic sequencing, and often RNA-Seq will be performed to identify the mutations expressed in the patient s cancer. Multiple autologous TIL cultures will be grown and tested for reactivity against mutations from the autologous tumor using assays we have developed that involve the exposure of autologous antigen-presenting cells to long peptides containing the mutation or tandem mini-genes encoding the mutation.

- T-cell cultures with reactivity against mutations will be identified and the individual T-cell receptors that recognize the mutation will be synthesized and used to create a retrovirus for transduction of the TCR into the patient s autologous PBL.

- Transduced autologous PBL will then be expanded to large numbers using our standard rapid expansion protocol and administered to the patient following a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine. Patients will then begin high-dose aldesleukin after the infusion of autologous transduced PBL. At the discretion of the Principal Investigator (PI), patients enrolled in Cohort 3 may receive low-dose aldesleukin.

- Clinical and immunologic response will be evaluated about 4-6 weeks after cell infusion and periodically thereafter.

- It is anticipated that approximately one patient per month may enroll on the trial for each of the four histologic groups. Thus, accrual of up to 4 x 50=200 total evaluable patients may be completed in approximately 2-4 years. In order to allow for a small number of inevaluable patients, the accrual ceiling will be set to 210. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT03412877
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact Ellen Bodurian
Phone (866) 820-4505
Status Recruiting
Phase Phase 2
Start date September 6, 2018
Completion date March 23, 2028

See also
  Status Clinical Trial Phase
Recruiting NCT03591848 - Pilot Study of a Web-based Decision Aid for Young Women With Breast Cancer, During the Proposal for Preservation of Fertility N/A
Recruiting NCT03095352 - A Randomized Phase II Study of Pembrolizumab, an Anti-PD (Programmed Cell Death)-1 Antibody, in Combination With Carboplatin Compared to Carboplatin Alone in Breast Cancer Patients With Chest Wall Disease Phase 2
Active, not recruiting NCT01472094 - Clinical and Biological Predictors of Chemotherapy Toxicity in Older Adults
Recruiting NCT03544762 - Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation Phase 3
Active, not recruiting NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Recruiting NCT03709134 - Genomic Markers for Measuring Metastatic Risk in Breast Cancer Following Primary Treatment
Recruiting NCT03667716 - COM701 in Subjects With Advanced Solid Tumors Phase 1
Active, not recruiting NCT02894398 - Study in Women With Advanced Breast Cancer Receiving Palbociclib With AI or Fulvestrant Phase 2
Active, not recruiting NCT01857193 - Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer Phase 1
Recruiting NCT01624090 - Mithramycin for Lung, Esophagus, and Other Chest Cancers Phase 2
Recruiting NCT03432429 - REI-EXCISE iKnife Study N/A
Active, not recruiting NCT02139358 - Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer Phase 1/Phase 2
Recruiting NCT03615573 - Survey Study: Financial Impact of Breast Cancer Treatment
Active, not recruiting NCT02295059 - Omega 3 Fatty Acids and ERPR(-)HER2(+/-) Breast Cancer Prevention N/A
Completed NCT03323333 - Psychosocial Intervention Pilot for Partners in BRCA Testing N/A
Terminated NCT01649258 - Fosaprepitant Dimeglumine and Granisetron Transdermal System in Preventing Nausea and Vomiting in Patients With Breast Cancer Undergoing Chemotherapy Phase 1
Withdrawn NCT03285607 - MCS110 Combined With Neoadjuvant Doxorubicin, Cyclophosphamide, and Weekly Paclitaxel in Patients With Hormone-Receptor Positive and HER2- Breast Cancer Phase 1
Completed NCT03384511 - The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies. Phase 4
Recruiting NCT01992432 - Brain Functional MRI in Older Women With Breast Cancer (Brain fMRI-BC)
Completed NCT01943500 - Collection of Blood Specimens for Circulating Tumor Cell Analysis N/A