Safety and Efficacy of CCT301 CAR-T in Adult Subjects With Recurrent or Refractory Stage IV Renal Cell Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03393936|
Recruitment Status : Active, not recruiting
First Posted : January 9, 2018
Last Update Posted : October 21, 2021
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma||Biological: CCT301-38 Biological: CCT301-59||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Factorial Assignment|
|Intervention Model Description:||Subjects with ROR2 positive biopsy will receive CCT301-59. Subjects with AXL positive biopsy that are ROR2 negative will receive CCT301-38.|
|Masking:||None (Open Label)|
|Official Title:||A Dose Escalation and Dose Expansion Trial to Assess the Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) CCT 301-38 or CCT 301-59 in Patients With Recurrent or Refractory Stage IV Renal Cell Carcinoma|
|Actual Study Start Date :||March 26, 2018|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||June 30, 2023|
The safety and efficacy of CCT301-59 will be evaluated for subjects with ROR2 positive biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10^5/kg, 1×10^6/kg, 1×10^7/kg CAR+ T cells.
Subjects will undergo blood draw to isolate peripheral blood mononuclear cells (PBMCs) for the production of CCT301-59. During CCT301-59 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocyte depletion. After lymphodepletion, subjects will receive one dose treatment with CCT301-59 by intravenous (IV) injection.
The safety and efficacy of CCT301-38 will be evaluated for subjects with AXL positive but ROR2 negative biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10^5/kg, 1×10^6/kg, 1×10^7/kg CAR+ T cells.
Subjects will undergo blood draw to isolate peripheral blood mononuclear cells (PBMCs) for the production of CCT301-38. During CCT301-38 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocyte depletion. After lymphodepletion, subjects will receive one dose treatment with CCT301-38 by intravenous (IV) injection.
- Phase I Safety (Incidence of adverse events defined as dose-limiting toxicities(DLT) [ Time Frame: Up to 28 days from cell infusion ]Incidence of adverse events defined as dose-limiting toxicities (DLT)
- Phase II Objective Response Rate [ Time Frame: Up to 9 months from cell infusion ]Objective Response Rate of confirmed complete and partial remission by independent radiology review RECIST (1.1)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 70 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Men or women aged 18~70 years old.
- Patients are diagnosed as refractory / recurrent, Stage IV renal cell carcinoma by histological method with FDG PET signal > 3 SUV in measurable metastatic lesion.
- Patients with at least two metastatic lesions, including one measurable metastatic tumor lesion >10 mm measurable by CT.
Tumor tissues samples confirmed CCT301 target positive IHC. Patient with histological biopsy.
- tumor tissue with greater than or equal to 50% positive staining by IHC method for ROR2 ;
- tumor tissue with greater than or equal to 50% positive staining by IHC method for AXL that is ROR2 negative.
- Expected survival ≥12 weeks.
- ECOG 0-1
Adequate organ function as documented by:
- ALT and AST≤2.5ULN; for liver metastasis, ALT and AST ≤5ULN
- Serum TBiL≤3.0mg/dL, TBiL≤2.5ULN
- PT: INR < 1.7 or extended PT to normal value < 4s
- Adequate venous access for venous blood collection, and no other contraindication of blood cell separation
- Patients with willingness to be in this study and able to provide informed consent
- Capable of receiving treatment and follow up, included patients are required to receive treatment in the enrolled centre
- Women of childbearing age are required to take acceptable measures to minimize the possibility of pregnancy during whole session. Women of childbearing age must have negative results of serum or urine tests within 24 hours prior to infusion. Women patients must not be in lactation;
- Pregnant women or women in lactation.
- Active HBV or HCV infection.
- HIV/AIDS infection.
- Active infection
- Previously suffered from diseases or concurrent diseases as follows:
- Patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
- Patients with previous diagnosis as motor neuron disease caused by autoimmunity
- Patients previously suffered from toxic epidermal necrolysis (TEN)
- Patients with any mental diseases including dementia, mental status change that may impinge the understanding and performance of informed consent and related questionnaire
- Patients with severe, uncontrollable diseases judged by investigator that may hinder them receiving this treatment
- Patients with other previously active malignant tumors including basal or squamous skin cancer, superficial bladder cancer, and in situ breast carcinoma within 5 years who had been completely cured without the need of follow-up treatment are not excluded.
- Ongoing treatment using systemic steroid or steroid inhalants.
- Previous treatment used gene/cell therapy products.
- Previous experience of immunotherapies including CIK, DC, DC-CIK, LAK for the treatment of cancer.
- Allergic to immunotherapies or related drugs
- Patients in need of treatment for heart failure with ≥2 NYHA or for poor controlled hypertension.
- Patients with unstable or active peptic ulcer or alimentary tract hemorrhage.
- Patients with previous organ transplantation or ready for organ transplantation.
- Patients in need of anticoagulant therapy treatment (warfarin or heparin)
- Patients judged by investigators as not appropriate for this study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03393936
|Shanghai Public Health Clinical Center|
|Shanghai, Shanghai, China, 200000|
|Principal Investigator:||Tongyu Zhu||Shanghai Public Health Clinical Center|
|Responsible Party:||Shanghai PerHum Therapeutics Co., Ltd.|
|Other Study ID Numbers:||
CCT301-mRCC01; Phase I/II
|First Posted:||January 9, 2018 Key Record Dates|
|Last Update Posted:||October 21, 2021|
|Last Verified:||October 2021|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
stage IV metastatic renal cell carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Male Urogenital Diseases