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Esophageal CancerPhase 2NCT05944809

The Effect of Prophylactic TPO Combined with BMS-IMRT to Esophageal Cancer Patients

A Phase 2 study testing rhTPO in people with Esophageal Cancer and Intensity-modulated Radiation Therapy, run by JIANYANG WANG at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this interventional study is to explore the protective effect of prophylactic TPO combined with bone marrow sparing (BMS)-IMRT in patients with esophageal cancer undergoing concurrent chemoradiotherapy. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
rhTPO
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteChina
Study dates
20 Jul 2023to 31 Dec 2024
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 greater than 18 years and less than or equal to 75 years
  • Histopathologically confirmed esophageal squamous/adenocarcinoma, clinical stage I-IV A (according to the 7th edition of AJCC（American Joint Committee on Cancer） 2010; Concurrent chemoradiotherapy (≥45Gy) was planned (regardless of whether the patient had received induction adjuvant chemotherapy).
  • Karnofsky performance status score ≥80 ·;
  • Life expectancy >6 months;
  • Meet the following laboratory diagnostic criteria:
  • Hemoglobin ≥120g/L, white blood cell ≥4.0×109/L, Neutrophil ≥2.0×109/L, platelet ≥100×109/L;
  • Participators had not used granulocyte colony-stimulating factor and thrombopoietin within 3 weeks before enrollment.

Who cannot join

  • A history of malignancy at other sites, excluding curable non-melanotic skin cancer and cervical carcinoma in situ;
  • Previous radiotherapy to the chest;
  • Patients with existing or suspected (thoracolumbar and pelvic) bone marrow or bone metastases, or a history of bone trauma in this region within 4 weeks;
  • Allergy to Gadolinium-based contrast agent;
  • Patients with active infection, or combined with rheumatic immune disease, long-term chronic infection, acute infection, etc., so that the body is in an inflammatory state; Blood system diseases with hematopoietic dysfunction;

Trial locations and contacts

1 site in 1 country.

China1 site

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

    Beijing, Beijing Municipality, 100021

Other trials in China

About this study

Official title: A Prospective Phase II Study of Prophylactic TPO Combined with Bone Marrow-sparing Intensity-modulated Radiotherapy to Reduce Platelet Inhibition in Patients with Esophageal Cancer Undergoing Concurrent Chemoradiotherapy

The goal of this interventional study is to explore the protective effect of prophylactic TPO combined with bone marrow sparing (BMS)-IMRT in patients with esophageal cancer undergoing concurrent chemoradiotherapy. The main purpose is to reduce the incidence of all grades of thrombocytopenia from 35% to less than 10% by the intervention of study.

Participants will initiate concurrent chemoradiotherapy within 2 weeks after enrollment,and they will receive subcutaneous injection of recombinant human thrombopoietin (rhTPO) 15000U once a week during the radiotherapy.

Read the detailed description

Concurrent chemoradiotherapy (CRT) is one of the standard treatments to the patients who initiate neoadjuvant chemoradiotherapy or radical radiotherapy. Previous large phase III trials of preoperative concurrent chemoradiotherapy and definitive chemoradiotherapy (Dt 40-60Gy) in esophageal cancer have shown rates of platelet inhibition (grade 1-4) of 25-54%. Concurrent chemotherapy has been associated with a significant increase in acute hematologic toxicity (HT) associated with radiation therapy, increasing the risk of infections, blood transfusions, colony-stimulating factors, and length of hospital stay. More importantly, severe myelosuppression also delays or interrupts the delivery of chemotherapy and radiotherapy, potentially reducing efficacy. In addition, the efficacy of locally advanced patients is still not optimistic, and the intensity of treatment may need to be increased. Therefore, if hematologic toxicity can be reduced, it may lead to more intensive concurrent chemoradiotherapy in the hope of further improving the efficacy.

Intensity-modulated radiation therapy (IMRT) has an absolute advantage over conventional radiotherapy in increasing the dose to the target volume and reducing the dose to normal tissues. Previous studies have shown a significant association between the volume of 10Gy (V10) and the volume received 20Gy (V20) of the pelvic and lumbosacral bone marrow and the development of acute HT when pelvic tumors are treated with IMRT. Thus, reducing the volume of bone marrow receiving low-dose radiotherapy may reduce the occurrence and severity of HT. Therefore, using the dosimetric advantages of IMRT, quantitative study of BMS-IMRT to reduce the toxic effects of concurrent chemoradiotherapy is a research hotspot at present.

Thrombopoietin (TPO) promotes the proliferation and survival of hematopoietic stem cells and all hematopoietic progenitor cells, accelerates the entry of stem cells into the cell cycle, and subsequently promotes the mitosis and polyploidy formation of megakaryocytes, increases the volume and number of megakaryocytes, and works with other cytokines to regulate megakaryocyte maturation. It is a commonly used drug for the treatment of thrombocytopenia in clinic.

The aim of this study is to explore the protective effect of prophylactic use of TPO on platelet inhibition in concurrent chemoradiotherapy using BMS-IMRT for esophageal cancer.

Being tested
rhTPO
Medical subject headings
Esophageal Neoplasms, Thrombocytopenia

What participants receive

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

  • rhTPODrug

    Also called BMS-IMRT, concurrent chemoradiotherapy

    Standard treatment options:

    Radiotherapy: 95% planning target volume （planning target volume，PTV） ≥45Gy(without simultaneous boost).

    Concurrent chemotherapy:

    Weekly regimen: paclitaxel 50mg/m2 d1, nedaplatin/cisplatin 25 mg/m2d1, a total of 5 cycles.

    Three weeks regimen: paclitaxel 135-175mg/m2 d1, nedaplatin/cisplatin 80mg/m2, a total of 2 cycles.

    The active bone marrow was determined by magnetic resonance（magnetic resonance，MR）, and the dose limits are: V5<95%,V10<85%,V20<60%，V30<40%；95%PTV>45Gy.

    rhTPO，15000U ih. qw(during the radiotherapy course)

Study groups in NCT05944809
Study groupRoleWhat they receive
prophylactic TPOExperimentalProphylactic TPO combined with BMS-IMRT in the esophageal cancer patients undergoing concurrent chemoradiotherapy
Receives: Drug: rhTPO

What is being measured

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

  1. The highest grade of thrombocytopenia (CTCAE 4.0) during the radiotherapy and 1 month after the radiotherapy.

    For esophageal cancer patients, Grade 1-4 thrombocytopenia is considered as endpoints.

    Measured: From start of radiotherapy and 1 month after the radiotherapy.

Secondary outcomes (4)

  1. Physical dosimetry of active bone marrow in BMS radiotherapy plan.

    Low dose volume, the volume of active BM receiving 5,10,20,30 and 40 Gy

    Measured: The first day of radiotherapy.

  2. Conformity of BMS IMRT/VMAT (Volumetric Modulated Arc Therapy，VMAT) plan

    Conformity Index (CI）was used to evaluate the conformity of IMRT/VMAT plan.

    Measured: The first day of radiotherapy.

  3. Homogeneity of IMRT/VMAT (Volumetric Modulated Arc Therapy，VMAT) plan

    Homogeneity Index (HI) was used to evaluate the homogeneity of BMS IMRT plan.

    Measured: The first day of radiotherapy.

  4. The highest grade of leukopenia, neutropenia,anemia (CTCAE 4.0) during the radiotherapy and 1 month after the radiotherapy.

    For esophageal cancer patients, Grade 1-4 leukopenia, neutropenia and anemia are considered as endpoints.

    Measured: From start of radiotherapy and 1 month after the radiotherapy.

Timeline

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

  1. First posted13 Jul 2023
  2. Study start20 Jul 2023
  3. Primary completion30 Jun 2024
  4. Study completion31 Dec 2024

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
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
All patients are planned to receive concurrent BMS thoracic radiotherapy (\>45Gy, 1.8Gy per fraction), chemotherapy (five cycles of weekly intravenous paclitaxel \[50 mg/m²\] and cisplatin/nedaplatin \[25 mg/m²\], or two cycles of intravenous paclitaxel \[135-175 mg/m²\] and cisplatin/nedaplatin \[80 mg/m²\]) , and rhTPO，15000U ih. qw(during the radiotherapy)
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05944809
Sponsor's protocol ID
NCC2818
Status last verified
Jan 2025
First submitted
2 Jun 2023
Last updated
24 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.

    PubMed 22646630

  • Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.

    PubMed 30089078

  • Chen Y, Ye J, Zhu Z, Zhao W, Zhou J, Wu C, Tang H, Fan M, Li L, Lin Q, Xia Y, Li Y, Li J, Jia H, Lu S, Zhang Z, Zhao K. Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. J Clin Oncol. 2019 Jul 10;37(20):1695-1703. doi: 10.1200/JCO.18.02122. Epub 2019 Mar 28.

    PubMed 30920880

  • Ji Y, Du X, Zhu W, Yang Y, Ma J, Zhang L, Li J, Tao H, Xia J, Yang H, Huang J, Bao Y, Du D, Liu D, Wang X, Li C, Yang X, Zeng M, Liu Z, Zheng W, Pu J, Chen J, Hu W, Li P, Wang J, Xu Y, Zheng X, Chen J, Wang W, Tao G, Cai J, Zhao J, Zhu J, Jiang M, Yan Y, Xu G, Bu S, Song B, Xie K, Huang S, Zheng Y, Sheng L, Lai X, Chen Y, Cheng L, Hu X, Ji W, Fang M, Kong Y, Yu X, Li H, Li R, Shi L, Shen W, Zhu C, Lv J, Huang R, He H, Chen M. Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1459-1466. doi: 10.1001/jamaoncol.2021.2705.

    PubMed 34351356

  • Li C, Tan L, Liu X, Wang X, Zhou Z, Chen D, Feng Q, Liang J, Lv J, Wang X, Bi N, Deng L, Wang W, Zhang T, Ni W, Chang X, Han W, Gao L, Wang S, Xiao Z. Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis. Thorac Cancer. 2021 Jun;12(12):1831-1840. doi: 10.1111/1759-7714.13971. Epub 2021 May 5.

    PubMed 33949784

  • Liu Y, Zheng Z, Li M, Zhang Y, Zhao F, Gong H, Lin H, Huang W, Chen X, Xu Z, Li X, Liu W, Cui Y, Zheng A, Li B. Comparison of concurrent chemoradiotherapy with radiotherapy alone for locally advanced esophageal squamous cell cancer in elderly patients: A randomized, multicenter, phase II clinical trial. Int J Cancer. 2022 Aug 15;151(4):607-615. doi: 10.1002/ijc.34030. Epub 2022 Apr 27.

    PubMed 35419831

  • Abu-Rustum NR, Lee S, Correa A, Massad LS. Compliance with and acute hematologic toxic effects of chemoradiation in indigent women with cervical cancer. Gynecol Oncol. 2001 Apr;81(1):88-91. doi: 10.1006/gyno.2000.6109.

    PubMed 11277656

  • Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6. doi: 10.1016/S0140-6736(01)05965-7.

    PubMed 11564482

  • Torres MA, Jhingran A, Thames HD Jr, Levenback CF, Bodurka DC, Ramondetta LM, Eifel PJ. Comparison of treatment tolerance and outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy in a prospective randomized trial or with standard treatment. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):118-25. doi: 10.1016/j.ijrobp.2007.05.028. Epub 2007 Sep 14.

    PubMed 17869451

  • Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1144-53. doi: 10.1056/NEJM199904153401502.

    PubMed 10202165

  • Nugent EK, Case AS, Hoff JT, Zighelboim I, DeWitt LL, Trinkhaus K, Mutch DG, Thaker PH, Massad LS, Rader JS. Chemoradiation in locally advanced cervical carcinoma: an analysis of cisplatin dosing and other clinical prognostic factors. Gynecol Oncol. 2010 Mar;116(3):438-41. doi: 10.1016/j.ygyno.2009.09.045. Epub 2009 Nov 5.

    PubMed 19896180

  • Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ. Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002 Dec 1;54(5):1388-96. doi: 10.1016/s0360-3016(02)03801-4.

    PubMed 12459361

  • Roeske JC, Lujan A, Rotmensch J, Waggoner SE, Yamada D, Mundt AJ. Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2000 Dec 1;48(5):1613-21. doi: 10.1016/s0360-3016(00)00771-9.

    PubMed 11121668

  • Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, Roeske JC. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1330-7. doi: 10.1016/s0360-3016(01)02785-7.

    PubMed 11955746

  • Gershkevitsh E, Rosenberg I, Dearnaley DP, Trott KR. Bone marrow doses and leukaemia risk in radiotherapy of prostate cancer. Radiother Oncol. 1999 Dec;53(3):189-97. doi: 10.1016/s0167-8140(99)00145-0.

    PubMed 10660197

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rhTPO in people with Esophageal Cancer and Intensity-modulated Radiation Therapy, run by JIANYANG WANG 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 7 inclusion and 5 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: finished, as of the sponsor's last update on 24 Jan 2025. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The highest grade of thrombocytopenia (CTCAE 4.0) during the radiotherapy and 1 month after the radiotherapy. (time frame: From start of radiotherapy and 1 month after the radiotherapy.). 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 NCT05944809, which also lists 20 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 24 Jan 2025.

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