Colorectal Cancer Stage IIIPhase 1/2NCT03904537
A Study of Combination of Anti-PD1 Antibody-activated TILs and Chemotherapy in Colorectal Cancer
A Phase 1/2 study testing anti-PD-1 antibody-activated TILs in people with Colorectal Cancer Stage III, run by Sun Yat-sen University at 1 site in China.
Trial summary
This study was a phase I/II trial initiated by the investigator to evaluate the safety and tolerability of anti-programmed cell death protein 1 (anti-PD1) antibody-activated autologous tumor-infiltrating lymphocytes (TILs) combined with adjuvant chemotherapy in participants with stage III colon cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer Stage III
- What is being tested?
- anti-PD-1 antibody-activated TILs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 19 Feb 2019to 31 Dec 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants with stage III colorectal cancer and scheduled to receive adjuvant chemotherapy postoperation.
- Age 18 to 75 years.
- Willing to sign a durable power of attorney.
- Able to understand and sign the Informed Consent Document.
- Life expectancy of greater than six months.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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- Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
- Adequate organ function.
- Serology:
- Seronegative for HIV antibody. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
- •Hematology: white blood cell count (> 3500/mm(3)). Platelet count greater than 100,000/mm(3). Hemoglobin greater than 9.0 g/dl.
- •Chemistry: Serum Alanine aminotransferase/Aspartate aminotransferase less or equal to 2.5 times the upper limit of normal.
- Serum creatinine less than or equal to 1.6 mg/dl. Total bilirubin less than or equal to 1.5 mg/dl.
Who cannot join
- Previous treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) , anti-PD-1, and anti-Programmed death-ligand 1(PD-L1).
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Allogeneic tissue/organ transplantation.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- History of autoimmune disease
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Concurrent antineoplastic therapies and systemic steroid therapy.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-Sen University, Cancer Center
Guangzhou, Guangdong, 510060
Jian-Chuan Xia, Ph.D., 86-20-87345699, xiajch@sysucc.org.cn
De-Sheng Weng, Ph.D., 86-20-87343404, wengds@sysucc.org.cn
About this study
Official title: A Phase I/II Study of Combination of Anti-Programmed Cell Death Protein 1(Anti-PD1) Antibody-activated Autologous Tumor Infiltrating Lymphocytes (TILs) and Chemotherapy in the Treatment of Stage III Colorectal Cancer.
This study was a phase I/II trial initiated by the investigator to evaluate the safety and tolerability of anti-programmed cell death protein 1 (anti-PD1) antibody-activated autologous tumor-infiltrating lymphocytes (TILs) combined with adjuvant chemotherapy in participants with stage III colon cancer. Twenty participants were enrolled and anti-PD1 antibody-activated TILs was infused into participants after the final of adjuvant chemotherapy to assess the safety and 3-year disease-free survival.
Read the detailed description
Postoperative colon cancer participants received 4 to 8 cycles of XELOX regimen adjuvant chemotherapy and received anti-PD1 antibody-activated TILs on the day 15 of the final cycle of chemotherapy.
Fresh tumor tissues or sentinel lymph nodes were collected from participants with postoperative colon cancer, and the tumor tissues were digested with type IV collagenase at 37 °C for 2 to 4 hours. The cell pellet was washed, suspended in medium containing 10% AB serum, planted in a 24-well cell culture plate, and periodically changed according to the growth of the cells. After culturing for 2 to 3 weeks, TILs were co-stimulated with radioactively irradiated allogeneic peripheral blood mononuclear cells (PBMCs) and were expanded in 100 ml of Interleukin-2 (IL-2) medium in a cell culture flask. After rapid expansion for 15 days, the number of cells reached 0.1-1*10^10 cells. Before cell transfer, TILs were incubated with anti-PD-1 antibody, and a fraction of the TILs were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous TILs (0.1-1*10^10 cells) were transferred to participants via intravenous infusion.
- Conditions
- Colorectal Cancer Stage III
- Being tested
- anti-PD-1 antibody-activated TILs
- Keywords
- Colorectal Cancer, TIL, immunotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-PD-1 antibody-activated TILsBiological
Participants would received one dose anti-PD-1 antibody-activated TILs at the final cycle of XELOX regimen chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| PD1-TIL combined with chemotherapy | Experimental | Participants would received anti-PD-1 antibody-activated TILs after the final adjuvant chemotherapy. Receives: Biological: anti-PD-1 antibody-activated TILs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival (DFS）
DFS is defined as the time from surgery until tumor recurrence or death.
Measured: 6 months
Secondary outcomes (4)
Overall survival (OS)
OS is defined as the time from surgery until death from any cause
Measured: 6 months
Severity of adverse events
According to National Cancer Institute Common Terminology Criteria for Adverse Events（NCI-CTCAE)
Measured: 3 weeks
Immune cell subgroup and cytokine level
The number and secreted cytokines of cluster of differentiation 3 (CD3+), CD8+, CD4+ or CD56+ T cells
Measured: 1 months
The quality of life by EQ-5D-5L (EuroQol Group, Chinese versions )
Participants were interviewed with the EQ-5D-5L (EuroQol Group, Chinese versions). There are numbers from 0 to 100 on this scale of the EQ-5D-5L. 100 represents the best health condition you can imagine, and 0 represents the worst health condition in your imagination. Please put an X on the scale to indicate how healthy you are today. And the number you marked on the scale represents your health condition today.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study start19 Feb 2019
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer Stage IIIStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianchuan Xia, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03904537
- Sponsor's protocol ID
- B2018-148-02
- Status last verified
- Apr 2019
- First submitted
- 31 Mar 2019
- Last updated
- 5 Apr 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We did not decide whether to share the subject's personal information.
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Combination of Anti-Programmed Cell Death Protein 1(Anti-PD1) Antibody-activated Autologous Tumor Infiltrating Lymphocytes (TILs) and Chemotherapy in the Treatment of Stage III Colorectal Cancer.
- ClinicalTrials.gov ID
- NCT03904537
- Acronym / sponsor ID
- B2018-148-02
- Conditions
- Colorectal Cancer Stage III
- Keywords
- Colorectal Cancer, TIL, immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 19 Feb 2019 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 5 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was a phase I/II trial initiated by the investigator to evaluate the safety and tolerability of anti-programmed cell death protein 1 (anti-PD1) antibody-activated autologous tumor-infiltrating lymphocytes (TILs) combined with adjuvant chemotherapy in participants with stage III colon cancer. Twenty participants were enrolled and anti-PD1 antibody-activated TILs was infused into participants after the final of adjuvant chemotherapy to assess the safety and 3-year disease-free survival.
Detailed description
Postoperative colon cancer participants received 4 to 8 cycles of XELOX regimen adjuvant chemotherapy and received anti-PD1 antibody-activated TILs on the day 15 of the final cycle of chemotherapy.
Fresh tumor tissues or sentinel lymph nodes were collected from participants with postoperative colon cancer, and the tumor tissues were digested with type IV collagenase at 37 °C for 2 to 4 hours. The cell pellet was washed, suspended in medium containing 10% AB serum, planted in a 24-well cell culture plate, and periodically changed according to the growth of the cells. After culturing for 2 to 3 weeks, TILs were co-stimulated with radioactively irradiated allogeneic peripheral blood mononuclear cells (PBMCs) and were expanded in 100 ml of Interleukin-2 (IL-2) medium in a cell culture flask. After rapid expansion for 15 days, the number of cells reached 0.1-1*10^10 cells. Before cell transfer, TILs were incubated with anti-PD-1 antibody, and a fraction of the TILs were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous TILs (0.1-1*10^10 cells) were transferred to participants via intravenous infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD1-TIL combined with chemotherapy | Experimental | Biological: anti-PD-1 antibody-activated TILsParticipants would received anti-PD-1 antibody-activated TILs after the final adjuvant chemotherapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants with stage III colorectal cancer and scheduled to receive adjuvant chemotherapy postoperation.
- Age 18 to 75 years.
- Willing to sign a durable power of attorney.
- Able to understand and sign the Informed Consent Document.
- Life expectancy of greater than six months.
Key exclusion criteria (7 listed)
- Previous treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) , anti-PD-1, and anti-Programmed death-ligand 1(PD-L1).
- Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Allogeneic tissue/organ transplantation.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- History of autoimmune disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-PD-1 antibody-activated TILsParticipants would received one dose anti-PD-1 antibody-activated TILs at the final cycle of XELOX regimen chemotherapy | Biological | PD1-TIL combined with chemotherapy |
Primary outcome
Disease-free survival (DFS）
Time frame: 6 months
DFS is defined as the time from surgery until tumor recurrence or death.
4 secondary outcomes
Overall survival (OS)
Time frame: 6 months
Severity of adverse events
Time frame: 3 weeks
Immune cell subgroup and cytokine level
Time frame: 1 months
The quality of life by EQ-5D-5L (EuroQol Group, Chinese versions )
Time frame: 3 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Individual participant dataSharing planned: Undecided. We did not decide whether to share the subject's personal information.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing anti-PD-1 antibody-activated TILs in people with Colorectal Cancer Stage III, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (DFS） (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2019.