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Metastatic Colorectal CancerPhase 2NCT03927898

Phase II Study of Toripalimab Plus Stereotactic Body Radiotherapy in Colorectal Cancer Patients With Oligometastasis

A Phase 2 study testing Toripalimab and Stereotactic Body Radiotherapy in people with Metastatic Colorectal Cancer, run by Chinese Academy of Medical Sciences at 3 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Metastatic colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The introduction of immune-checkpoint inhibition (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Toripalimab and Stereotactic Body Radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
3 sitesChina
Study dates
1 Mar 2019to 1 Sep 2021
Phase
Phase 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

  • Age：18-75 years old , Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Histologically confirmed CRC , metastatic CRC , subjects have received first-line systemic therapy for more than 3 months and achieved PR/SD, the interval between last systemic therapy and SBRT is≥4 weeks
  • The primary site has been controlled by surgery
  • Patient has at least 1 lesion of measurable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and iRECIST , and who can achieve the status of non evidence of disease after local ablative therapy. The number of lesion is ≤ 5, the maximum diameter of the lesion is ≤5cm ,
  • All metastatic lesions are amenable to SBRT with BED≥80Gy in 3 to 5 fractions;
  • Have a life expectancy of at least 6 months
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  • Adequate organ function, as defined by the following:
  • Hemoglobin ≥ 100 g/L; White blood cell count (WBC) ≥3.5×109/L , Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelets ≥75×109/L; Serum creatinine ≤ 1.0 x institutional upper limit of normal (ULN) ; Blood Urea Nitrogen(BUN) ≤ 1.0 x institutional (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 x institutional ULN ALkaline Phosphatase (ALP) ≤ 1.5 x institutional ULN Serum total bilirubin (TBIL) ≤1.5 x institutional ULN Urine protein is negative , Coagulation function is normal
  • patients and his/her mate must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug；
  • Patient must have the ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Serious autoimmune disease at the discretion of the treating attending，subjects with leukodermia，allergic asthma syndrome will not be excluded from the study.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis requiring systemic steroids.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study Day 1 of the trial treatment.
  • Has a known additional malignancy，subjects with basal cell carcinoma (BCC)， squamous cell carcinoma of skin and carcinoma in situ of cervix will not be excluded from the study.
  • Has received a vaccine within 30 days prior to study Day 1 of the trial treatment or will receive a vaccine after the trial treatment; active HBV，HCV infection
Show all 10Show fewer
  • Has received systemic therapy within 4 weeks prior to study Day 1 of the trial treatment or who has not recovered from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy or myelosuppression are an exception to this criterion and may qualify for the study.
  • Any underlying medical or psychiatric condition: partial endocrine organ deficiencies , serious cardiac，pulmonary，renal disease，active infectious disease.
  • Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis , frequent diarrhea or other known risk factors for bowel perforation.

Trial locations and contacts

3 sites in 1 country.

Jing Jin, M.D contact

+86-1087787568

jingjin1025@163.com

Jianyang Wang, M.D. contact

+86-1087788122

pkucell@163.com

China3 sites, 3 recruiting

  • Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

    Beijing, Beijing Municipality, 100021

    Wenyang Liu, MD, liuwenyang26@163.com

    Recruiting

  • Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

    Beijing, Beijing Municipality, 100021

    Jianyang Wang, MD, +86-13810095191, pkucell@163.com

    Jing Jin, MD, +86-10-87788122, jingjin1025@163.com

    Recruiting

  • Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

    Beijing, 100021

    Jing Jin, MD, +8613601365130, jingjin1025@163.com

    Recruiting

Other trials in China

About this study

Official title: Phase II Study of Toripalimab (JS001) Plus Stereotactic Body Radiotherapy in Colorectal Cancer Patients With Oligometastasis

Metastatic colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The introduction of immune-checkpoint inhibition (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer. Stereotactic body radiation therapy (SBRT) delivers a large dose of radiation to the tumor target with high precision while sparing irradiation of the surrounding normal tissues. It is suggested that SBRT could be the most appropriate radiotherapy modality to be combined with immunotherapy since it induces the expression of a series of cytokines and new tumour-associated antigens (TAAs) and is more likely to cause intense immune response and exert an abscopal effect than conventional radiotherapy.

Thus, this study is to explore the use of SBRT in combination with ICI in colorectal cancer patients with oligometastasis, in order to get better local and systemic tumor control and improve progress-free survival (PFS).

Read the detailed description

The investigators plan to recruit patients with mCRC, who have received first-line systemic therapy for more than 3 months and achieved PR/SD. Than all the patients will receive SBRT followed by ICI therapy.

Being tested
Toripalimab, Stereotactic Body Radiotherapy
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ToripalimabDrug

    Participants receive Toripalimab (240mg)/q3w till progression of disease after SBRT

  • Stereotactic Body RadiotherapyRadiation

    Participants receive SBRT (BED>80Gy) to oligometastatic lesions followed by Toripalimab (240mg)/q3w

Study groups in NCT03927898
Study groupRoleWhat they receive
SBRT+ToripalimabExperimentalParticipants received SBRT (BED>80Gy) to oligometastatic lesions and then receive Toripalimab (240mg)/q3w till progression of disease.
Receives: Drug: Toripalimab; Radiation: Stereotactic Body Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1 year Progression-Free-Survival (PFS)

    1 year PFS

    Measured: 1 year

Secondary outcomes (8)

  1. Grade 3-5 acute adverse events

    Grade 3-5 acute adverse events

    Measured: 6 months since last treatment of Toripalimab

  2. Objective response rate

    Objective response rate

    Measured: At the end of 4 cycles of Toripalimab (each cycle is 21 days)

  3. 2 year local control rate

    2 year local control rate

    Measured: 2 year

  4. 2 year overall survival

    2 year overall survival

    Measured: 2 year

  5. T cell receptor repertoire and T cell clones in peripheral blood

    Change of T cell receptor repertoire and T cell clones in peripheral blood

    Measured: At the end of 6 cycles of Toripalimab (each cycle is 21 days)

  6. Expression of PD-1, ki-67 on T cell

    Change of expression of PD-1, ki-67 on T cell

    Measured: At the end of 6 cycles of Toripalimab (each cycle is 21 days)

  7. Expression of PD-L1 on Exosomes in peripheral blood

    Change of expression of PD-L1 on Exosomes in peripheral blood

    Measured: At the end of 6 cycles of Toripalimab (each cycle is 21 days)

  8. Expression of PD-L1 on circulation tumor cell

    Change of expression of PD-L1 on circulation tumor cell

    Measured: At the end of 6 cycles of Toripalimab (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2019
  2. Study start1 Mar 2019
  3. Primary completion1 Mar 2021 (estimated)
  4. Study completion1 Sep 2021 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
All enrolled patients will receive Toripalimab following stereotactic body radiotherapy
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03927898
Sponsor's protocol ID
18-223/1781
Status last verified
Apr 2019
First submitted
9 Apr 2019
Last updated
25 Apr 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.

    PubMed 27380959

  • Petrelli F, Comito T, Barni S, Pancera G, Scorsetti M, Ghidini A; SBRT for CRC liver metastases. Stereotactic body radiotherapy for colorectal cancer liver metastases: A systematic review. Radiother Oncol. 2018 Dec;129(3):427-434. doi: 10.1016/j.radonc.2018.06.035. Epub 2018 Jul 9.

    PubMed 29997034

  • Joo JH, Park JH, Kim JC, Yu CS, Lim SB, Park IJ, Kim TW, Hong YS, Kim KP, Yoon SM, Park J, Kim JH. Local Control Outcomes Using Stereotactic Body Radiation Therapy for Liver Metastases From Colorectal Cancer. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):876-883. doi: 10.1016/j.ijrobp.2017.07.030. Epub 2017 Jul 31.

    PubMed 29063852

  • Luke JJ, Lemons JM, Karrison TG, Pitroda SP, Melotek JM, Zha Y, Al-Hallaq HA, Arina A, Khodarev NN, Janisch L, Chang P, Patel JD, Fleming GF, Moroney J, Sharma MR, White JR, Ratain MJ, Gajewski TF, Weichselbaum RR, Chmura SJ. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol. 2018 Jun 1;36(16):1611-1618. doi: 10.1200/JCO.2017.76.2229. Epub 2018 Feb 13.

    PubMed 29437535

  • Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009 Jul 16;114(3):589-95. doi: 10.1182/blood-2009-02-206870. Epub 2009 Apr 6.

    PubMed 19349616

  • Tang C, Welsh JW, de Groot P, Massarelli E, Chang JY, Hess KR, Basu S, Curran MA, Cabanillas ME, Subbiah V, Fu S, Tsimberidou AM, Karp D, Gomez DR, Diab A, Komaki R, Heymach JV, Sharma P, Naing A, Hong DS. Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells. Clin Cancer Res. 2017 Mar 15;23(6):1388-1396. doi: 10.1158/1078-0432.CCR-16-1432. Epub 2016 Sep 20.

    PubMed 27649551

  • Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengelov L, Hansen S, Logothetis C, Beer TM, McHenry MB, Gagnier P, Liu D, Gerritsen WR; CA184-043 Investigators. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):700-12. doi: 10.1016/S1470-2045(14)70189-5. Epub 2014 May 13.

    PubMed 24831977

  • Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D'Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017 May 4;545(7652):60-65. doi: 10.1038/nature22079. Epub 2017 Apr 10.

    PubMed 28397821

  • Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, Yu Z, Yang J, Wang B, Sun H, Xia H, Man Q, Zhong W, Antelo LF, Wu B, Xiong X, Liu X, Guan L, Li T, Liu S, Yang R, Lu Y, Dong L, McGettigan S, Somasundaram R, Radhakrishnan R, Mills G, Lu Y, Kim J, Chen YH, Dong H, Zhao Y, Karakousis GC, Mitchell TC, Schuchter LM, Herlyn M, Wherry EJ, Xu X, Guo W. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018 Aug;560(7718):382-386. doi: 10.1038/s41586-018-0392-8. Epub 2018 Aug 8.

    PubMed 30089911

  • Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, Lin NU, Litiere S, Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, Caramella C, de Vries EGE; RECIST working group. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar;18(3):e143-e152. doi: 10.1016/S1470-2045(17)30074-8. Epub 2017 Mar 2.

    PubMed 28271869

  • Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, van As N, Tree A, Hatfield P, Harrow S, McDonald F, Ahmed M, Saran FH, Webster GJ, Khoo V, Landau D, Eaton DJ, Hawkins MA. UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin Oncol (R Coll Radiol). 2018 Jan;30(1):5-14. doi: 10.1016/j.clon.2017.09.007. Epub 2017 Oct 13.

    PubMed 29033164

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Toripalimab and Stereotactic Body Radiotherapy in people with Metastatic Colorectal Cancer, run by Chinese Academy of Medical Sciences at 3 sites 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 10 inclusion and 10 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 25 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 3 sites 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 phase mean?

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?

Contact Jing Jin, M.D (+86-1087787568, jingjin1025@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1 year Progression-Free-Survival (PFS) (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03927898, which also lists 11 linked publications.

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 25 Apr 2019.

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