Trial Title:
STIL101 for Injection for the Treatment of Locally Advanced, Metastatic or Unresectable Pancreatic Cancer, Colorectal Cancer, Renal Cell Cancer, Cervical Cancer and Melanoma
NCT ID:
NCT06626256
Condition:
Locally Advanced Cervical Carcinoma
Locally Advanced Colorectal Carcinoma
Locally Advanced Malignant Solid Neoplasm
Locally Advanced Melanoma
Locally Advanced Pancreatic Ductal Adenocarcinoma
Locally Advanced Renal Cell Carcinoma
Metastatic Cervical Carcinoma
Metastatic Colorectal Carcinoma
Metastatic Malignant Solid Neoplasm
Metastatic Melanoma
Metastatic Pancreatic Ductal Adenocarcinoma
Metastatic Renal Cell Carcinoma
Stage II Pancreatic Cancer AJCC v8
Stage III Cervical Cancer AJCC v8
Stage III Colorectal Cancer AJCC v8
Stage III Pancreatic Cancer AJCC v8
Stage III Renal Cell Cancer AJCC v8
Stage IV Cervical Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Stage IV Renal Cell Cancer AJCC v8
Unresectable Cervical Carcinoma
Unresectable Colorectal Carcinoma
Unresectable Malignant Solid Neoplasm
Unresectable Melanoma
Unresectable Pancreatic Ductal Adenocarcinoma
Unresectable Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma
Neoplasms
Colorectal Neoplasms
Melanoma
Adenocarcinoma
Pancreatic Neoplasms
Uterine Cervical Neoplasms
Carcinoma, Renal Cell
Kidney Neoplasms
Aldesleukin
Cyclophosphamide
Fludarabine
Interleukin-2
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Aldesleukin
Description:
Given SC
Arm group label:
Treatment (STIL101 for injection)
Other name:
125-L-Serine-2-133-interleukin 2
Other name:
Proleukin
Other name:
r-serHuIL-2
Other name:
Recombinant Human IL-2
Other name:
Recombinant Human Interleukin-2
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (STIL101 for injection)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (STIL101 for injection)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (STIL101 for injection)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Treatment (STIL101 for injection)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Asta B 518
Other name:
B 518
Other name:
B-518
Other name:
B518
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR 138719
Other name:
WR- 138719
Other name:
WR-138719
Other name:
WR138719
Intervention type:
Procedure
Intervention name:
Excisional Biopsy
Description:
Undergo excisional biopsy
Arm group label:
Treatment (STIL101 for injection)
Other name:
Biopsy, Excisional
Other name:
surgical biopsy
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Given IV
Arm group label:
Treatment (STIL101 for injection)
Other name:
Fluradosa
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (STIL101 for injection)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Standard Treatment
Description:
Receive standard of care therapy
Arm group label:
Treatment (STIL101 for injection)
Intervention type:
Biological
Intervention name:
Therapeutic Tumor Infiltrating Lymphocytes
Description:
Given STIL101 for injection IV
Arm group label:
Treatment (STIL101 for injection)
Other name:
Tumor Infiltrating Lymphocytes
Summary:
This phase I trial tests the safety and side effects of STIL101 for injection and how
well it works in treating patients with pancreatic cancer, colorectal cancer (CRC), renal
cell cancer (RCC), cervical cancer (CC) and melanoma that has spread to nearby tissue or
lymph nodes (locally advanced) or to other places in the body (metastatic) or that cannot
be removed by surgery (unresectable). STIL101 for injection, an autologous (made from the
patients own cells) cellular therapy, is made up of specialized white blood cells called
lymphocytes or "T cells" collected from a piece of the patients tumor tissue. The T cells
collected from the tumor are then grown in a laboratory to create STIL101 for injection.
STIL101 for injection is then given to the patient where it may attack the tumor. Giving
chemotherapy, such as cyclophosphamide and fludarabine, helps prepare the body to receive
STIL101 for injection in a way that allows the T cells the best opportunity to attack the
tumor. Aldesleukin is a form of interleukin-2, a cytokine made by leukocytes. Aldesleukin
increases the activity and growth of white blood cells called T lymphocytes and B
lymphocytes. Giving STIL101 for injection may be safe, tolerable and/or effective in
treating patients with locally advanced, metastatic or unresectable pancreatic cancer,
CRC, RCC, CC and melanoma.
Detailed description:
PRIMARY OBJECTIVE:
I. Determine the safety of administering STIL101 for injection in subjects with locally
advanced, unresectable, or metastatic pancreatic ducal adenocarcinoma (PDAC), CRC, RCC CC
or melanoma.
SECONDARY OBJECTIVES:
I. Summarize the efficacy observed due to STIL101 for injection in patients with locally
advanced, unresectable or metastatic PDAC, CRC, RCC, CC or melanoma:
Ia. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST)
1.1 and Immune-Modified (i)RECIST 1.0; Ib. Disease control rate (DCR) as measured from
STIL101 infusion; Ic. Overall survival (OS) as measured from STIL101 infusion; Id.
Progression-free survival (PFS) as measured from STIL101 infusion. II. Summarize
pre-STIL101 for injection therapy and outcomes from first study-related procedure.
III. Evaluate the feasibility and timing of generating STIL101 for injection. IV.
Describe STIL101 cell count in patients with respect to baseline characteristics,
clinical outcome and adverse events.
EXPLORATORY OBJECTIVE:
I. Biological correlatives associated with STIL101 for injection creation and infusion.
OUTLINE:
Patients undergo excisional biopsy and continue receiving standard of care therapy for
3-4 months prior to the start of study therapy. Patients with successful generation of
STIL101 for injection receive cyclophosphamide intravenously (IV) over 2 hours on days -5
to -4, fludarabine IV over 30 minutes on days -5 to -1 and STIL101 for injection IV on
day 0 in the absence of disease progression or unacceptable toxicity. Patients also
receive aldesleukin subcutaneously (SC) once daily (QD) on day 0 for up to 6-10 days.
Additionally, patients undergo blood sample collection, biopsy, computed tomography (CT)
and optional magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up at days 42, 56, 70 and 84
then every 2-4 weeks up to week 96 or progression. Patients who discontinued treatment
are followed up every 6 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative.
- Assent, when appropriate, will be obtained per institutional guidelines
- Agree to research biopsies while on-study
- Note: For research participants who do not speak English, a short form consent
may be used with a City of Hope (COH) certified interpreter/translator to
proceed with screening, while the request for a translated full consent is
processed
- Age: ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) ≤ 1
- Anticipated life expectancy of > 6 months at the time of enrollment
- Participants with pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CC),
renal cell carcinoma (RCC), cervical cancer (CC) and melanoma, meeting the following
criteria will be eligible:
- Cytologically or histologically confirmed locally advanced, unresectable, or
metastatic PDAC, CRC, RCC, CC, melanoma
- Patients must have received at least 1 line of standard therapy prior to
receiving STIL101 for injection. Note: Patients may be enrolled prior to
starting treatment to harvest tumor and blood samples for tumor infiltrating
lymphocyte (TIL) generation
- For pancreatic cancer patients:
- Patients on first line treatment will need to receive at least 4 months of
standard chemotherapy before receiving STIL101 for injection
- In the second line setting, these patients may opt to receive STIL101 for
injection at any time
- For melanoma cancer patients: Patients need to have received prior PD1 therapy
and BRAF inhibitor treatment in patients with a V600E mutation
- For RCC, CRC, CC patients: Patients need to have failed at least 1 line of
prior therapy
- Measurable disease by RECIST 1.1
- At least one lesion (or aggregate of lesions resected) that can be safety biopsied
(excisional) and yield a volume (target of > 1cm^3) to generate STIL101 for
injection (principal investigator [PI] discretion)
- Absolute neutrophil count (ANC) ≥ 1,000/mm^3
- NOTE: Growth factor is not permitted within 14 days of screening ANC assessment
- Platelets ≥ 100,000/mm^3
- NOTE: Platelet transfusions are not permitted within 14 days of screening
platelet assessment
- Hemoglobin ≥ 8 g/dL
- NOTE: Red blood cell transfusions are not permitted within 14 days of screening
platelet assessment
- Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless participant has Gilbert's
disease which allows total bilirubin ≤ 3 x ULN)
- Aspartate aminotransferase (AST) ≤ 3 x ULN; ≤ 5.0 x ULN if hepatic metastases are
present
- Alanine transaminase (ALT) ≤ 3 x ULN; ≤ 5.0 x ULN if hepatic metastases are present
- Creatinine clearance (CRCl) of ≥ 40 mL/min per 24-hour urine test or the
Cockcroft-Gault formula
- Oxygen (O2) saturation > 92% on room air not requiring oxygen supplementation
- Note: To be performed within 28 days prior to start of protocol therapy
- Left ventricular ejection fraction (LVEF) ≥ 50%
- Note: To be performed within 8 weeks prior to start of protocol therapy
- If not receiving anticoagulants: International normalized ratio (INR) or prothrombin
(PT) ≤ 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range
of intended use of anticoagulants
- If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5
x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of
intended use of anticoagulants
- Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV),
hepatitis B virus (HBV) (surface antigen negative), and syphilis (RPR)
- If seropositive for HCV or HBV, nucleic acid quantitation must be performed.
Viral load must be undetected
- QuantiFERON-TB Gold or equivalent
- Results do not impact patient eligibility; however, the test must be initiated
prior to enrollment
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
- Agreement by females and males of childbearing potential to use an effective method
of birth control or abstain from heterosexual activity for the course of the study
through at least 6 months after the last dose of protocol therapy
- Childbearing potential defined as not being surgically sterilized (men and
women) or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
- Prior organ transplant
- Concomitant herbal medications with exception to cannabidiol (CBD), which is allowed
- Continuous systemic steroid therapy (i.e., > 10 mg/day of prednisone or other
steroid equivalent dose) or other immunosuppressive therapies. Physical replacement
doses (i.e., adrenocortical insufficiency), inhaled or topical steroids at ≤ 10
mg/day of prednisone or another steroid equivalent dose are permissible in the
absence of active auto-immune disease
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to study agents, including history of hypersensitivity to any
drugs of the aminoglycoside group
- Prior or current known uveitis within 6 months of informed consent
- Active viral, bacterial, or fungal infection requiring treatment. Patients must be
seronegative for the human immunodeficiency virus (HIV) and syphilis (RPR). Patients
with hepatitis infections are allowed with undetected viral load
- Primary immunodeficiency (such as severe combined immunodeficiency [SCID] or
acquired immunodeficiency syndrome [AIDS])
- End-stage renal disorder requiring hemodialysis
- Class III/IV cardiovascular disability according to the New York Heart Association
(NYHA) Classification
- Known clinically significant pulmonary conditions within 6 months of informed
consent
- Prior or concurrent malignancy. Prior malignancies with a low probability of
recurrence requiring treatment such as the following are allowed: carcinoma in situ
of the cervix, nonmelanoma skin cancer and low grade (Gleason score ≤ 6=Gleason
group 1) localized prostate cancer. Prior malignancies not listed require PI
approval
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Contact:
Last name:
Vincent Chung
Phone:
626-471-9200
Email:
vchung@coh.org
Investigator:
Last name:
Vincent Chung
Email:
Principal Investigator
Start date:
December 30, 2024
Completion date:
October 30, 2027
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06626256
