Autologous Tumor Infiltrating Lymphocytes MDA-TIL in Treating Patients With Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, or Pancreatic Ductal Adenocarcinoma

Phase 2

Terminated

• Conditions: Malignant Solid Neoplasm; Metastatic Colorectal Adenocarcinoma; Metastatic Ovarian Carcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Platinum-Resistant Ovarian Carcinoma; Recurrent High Grade Ovarian Serous Adenocarcinoma; Recurrent Ovarian Carcinosarcoma; Refractory Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8

• Registration Number: NCT03610490
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-7-24
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Terminated
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Inclusion Criteria:<br><br> - Subjects must be willing and able to provide informed consent<br><br> - Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 at<br> enrollment and within 7 days of initiating lymphodepleting chemotherapy<br><br> - Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may<br> be allowed) for the generation of TIL separate from, and in addition to, a target<br> lesion to be used for response assessment<br><br> - Any prior therapy directed at the malignant tumor, including radiation therapy,<br> chemotherapy, and biologic/targeted agents must be discontinued at least 28 days<br> prior to tumor resection for preparing TIL therapy<br><br> - Absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days of enrollment)<br><br> - Hemoglobin >= 9.0 g/dL (transfusion allowed) (within 7 days of enrollment)<br><br> - Platelet count >= 100,000/mm^3 (within 7 days of enrollment)<br><br> - Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) and<br> aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) <<br> 2.5 x the upper limit of normal (ULN)<br><br> - Patients with liver metastases may have liver function test [LFT] =< 5.0 x ULN<br> (within 7 days of enrollment)<br><br> - Calculated creatinine clearance (Cockcroft-Gault) >= 50.0 mL/min (within 7 days of<br> enrollment)<br><br> - Total bilirubin =< 1.5 x ULN (within 7 days of enrollment)<br><br> - Prothrombin time (PT) & activated partial thromboplastin time (aPTT) =< 1.5 x ULN<br> (correction with vitamin K allowed) unless subject is receiving anticoagulant<br> therapy (which should be managed according to institutional norms prior to and after<br> excisional biopsy) (within 7 days of enrollment)<br><br> - Negative serum pregnancy test (female subjects of childbearing potential) (within 7<br> days of enrollment)<br><br> - Subjects must not have a confirmed human immunodeficiency virus (HIV) infection<br><br> - Subjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and<br> Fridericia's corrected QT interval (QTcF) less than 480 ms<br><br> - Subjects must also have a negative dobutamine stress echocardiogram before beginning<br> treatment<br><br> - Subjects of childbearing potential must be willing to practice an approved highly<br> effective method of birth control starting at the time of informed consent and for 1<br> year after the completion of the lymphodepletion regimen. Approved methods of birth<br> control are as follows: hormonal contraception (i.e. birth control pills, injection,<br> implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation<br> or hysterectomy; subject/partner status post vasectomy; implantable or injectable<br> contraceptives; and condoms plus spermicide<br><br> - Able to adhere to the study visit schedule and other protocol requirements<br><br> - Pulmonary function tests (spirometry) demonstrating forced expiratory value (FEV) 1<br> greater than 65% predicted or forced vital capacity (FVC) greater than 65% of<br> predicted<br><br> - Ovarian cancer cohort only: Subjects must have high grade non-mucinous histology<br> (carcinosarcomas are allowed)<br><br> - Ovarian cancer cohort only: Subjects must have failed at least two prior lines of<br> chemotherapy (i.e. frontline adjuvant chemotherapy plus one additional line for<br> recurrent/progressive disease), or have platinum resistant disease<br><br> - Colorectal cohort only: Subjects with colorectal adenocarcinoma must have metastatic<br> disease that is considered incurable with currently available therapies and have<br> derived maximal benefit from or have become refractory to frontline conventional<br> therapy (e.g. leucovorin calcium [calcium folinate], 5-fluorouracil and oxaliplatin<br> [FOLFOX], leucovorin calcium, 5-fluorouracil, and irinotecan [FOLFIRI]).<br><br> - Colorectal cohort only: Subjects should have low disease burden such that in the<br> treating physician's opinion the patient would not require additional intervening<br> treatment for 7-8 weeks (required for TIL harvest and manufacturing)<br><br> - Pancreatic adenocarcinoma cohort only: Subjects must have histologically or<br> cytologically documented diagnosis of PDAC with oligo-metastatic disease<br><br> - Pancreatic adenocarcinoma cohort only: Subjects must have progressed on, or received<br> maximal benefit from, front-line therapy<br><br> - Pancreatic adenocarcinoma cohort only: Patients may have received unlimited lines of<br> prior standard of care therapy<br><br> - Pancreatic adenocarcinoma cohort only: Patients with ascites or carcinomatosis are<br> not eligible for the study<br><br> - Pancreatic adenocarcinoma cohort only: Patients will need an albumin of >= 3.0 mg/dL<br> within 7 days of enrollment<br><br> - TREATMENT INCLUSION CRITERION: Within 24 h of starting lymphodepleting chemotherapy,<br> subjects must meet the following laboratory criteria:<br><br> - Absolute neutrophil count (ANC) >= 1000/mm^3<br><br> - Hemoglobin >= 9.0 g/dL (transfusion allowed)<br><br> - Platelet count >= 100,000/mm3<br><br> - ALT/SGPT and AST/SGOT =< 2.5 x the upper limit of normal (ULN)<br><br> - Patients with liver metastases may have liver function tests (LFT) =< 5.0<br> x ULN<br><br> - Calculated creatinine clearance (Cockcroft-Gault) >= 50.0 mL/min<br><br> - Total bilirubin =< 1.5 X ULN<br><br>Exclusion Criteria:<br><br> - Active systemic infections requiring intravenous antibiotics, coagulation disorders<br> or other major medical illnesses of the cardiovascular, respiratory or immune<br> system. Principal investigator (PI) or his/her designee shall make the final<br> determination regarding appropriateness of enrollment<br><br> - Patients with active viral hepatitis<br><br> - Patients who have a left ventricular ejection fraction (LVEF) < 45% at screening<br><br> - Patients with a history of prior adoptive cell therapies<br><br> - Persistent prior therapy-related toxicities greater than grade 2 according to Common<br> Toxicity Criteria for Adverse Events (CTCAE) v. 4.03, except for peripheral<br> neuropathy, alopecia, or vitiligo prior to enrollment<br><br> - Primary immunodeficiency<br><br> - History of organ or hematopoietic stem cell transplant<br><br> - Chronic steroid therapy, however prednisone or its equivalent is allowed at < 10<br> mg/day<br><br> - Patients who are pregnant or nursing<br><br> - Presence of a significant psychiatric disease, which in the opinion of the principal<br> investigator or his/her designee, would prevent adequate informed consent<br><br> - History of clinically significant autoimmune disease including active, known, or<br> suspected autoimmune disease. Subjects with resolved side effects from prior<br> checkpoint inhibitor therapy, vitiligo, psoriasis, type 1 diabetes or resolved<br> childhood asthma/atopy would be an exception to this rule. Subjects that require<br> intermittent use of bronchodilators or local steroid injections would not be<br> excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's<br> syndrome will not be excluded<br><br> - History of clinically significant chronic obstructive pulmonary disease (COPD),<br> asthma, or other chronic lung disease<br><br> - History of a second malignancy (diagnosed in the last 5 years). Exceptions include<br> basal cell carcinoma of the skin, squamous cell carcinom

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)

Secondary Outcome Measures

Name	Time	Method
Complete response rate (CRR);Disease control rate (DCR);Duration of response (DOR);Progression-free survival (PFS);Overall survival (OS);Incidence of adverse events