Comparison of Interleukin-11 and rhTPO for Recurrent Colorectal Cancer Patients With Thrombocytopenia

Sponsor

Fudan University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03823079

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This randomized controlled clinical phase II study was designed to compare the effect of rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent colorectal cancer who underwent radiotherapy and with thrombocytopenia.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Colorectal Carcinoma Thrombopenia	Drug: rhTPO Drug: irinotecan Drug: Raltitrexed Radiation: radiotherapy Drug: rhIL-11	Phase 2

Detailed Description

Most patients with recurrent CRC have undergone a six-month postoperative adjuvant chemotherapy with oxaliplatin plus fluorouracil. Although the main dose-limiting side effect of oxaliplatin is neurotoxicity, with the widespread use of this drug, there are more and more reports that oxaliplatin is discontinued because of thrombocytopenia, which increases the risk of bleeding, rate of blood transfusion needs and length of stay. On the other hand, patients undergoing pelvic radiotherapy may also experience significant bone marrow suppression because flat bones such as the tibia may be exposed to high doses radiation. Low platelet counts is an urgent problem to be solved in order to give adequate quantitative radiotherapy. This randomized controlled clinical phase II study was designed to compare the effect of rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent colorectal cancer who underwent radiotherapy and with thrombocytopenia, thus providing more evidence in clinical practice.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Recombinant Human Thrombopoietin (Rh-TPO) and Recombinant Human Interleukin-11 (rhIL-11) for Recurrent Colorectal Cancer (CRC) Patients With Thrombocytopenia

Anticipated Study Start Date :

Feb 1, 2019

Anticipated Primary Completion Date :

Sep 1, 2019

Anticipated Study Completion Date :

Feb 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rhTPO arm rhTPO: 300 u/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal) Concurrent Chemoradiotherapy: Radiation: judged according to the tumor site and radiotherapy purpose. Irinotecan: 80 mg/m2 (UGT1A128 6/6) or 65 mg/m2 (UGT1A128 6/7) Raltitrexed: 3 mg/m2 q3w	Drug: rhTPO rhTPO 300u/kg, subcutaneous injection, qd Drug: irinotecan 80mg/m2 (UGT1A128 6/6) or 65mg/m2 (UGT1A128 6/7) Drug: Raltitrexed 3mg/m2 q3w Radiation: radiotherapy in the use of intensity-modulated radiotherapy (IMRT) technology, the dose is judged according to the tumor site and radiotherapy purpose.
Active Comparator: rhIL-11 arm rhIL-11: 50 ug/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal) Concurrent Chemoradiotherapy: Radiation: judged according to the tumor site and radiotherapy purpose. Irinotecan: 80 mg/m2 (UGT1A128 6/6) or 65 mg/m2 (UGT1A128 6/7) Raltitrexed: 3 mg/m2 q3w	Drug: irinotecan 80mg/m2 (UGT1A128 6/6) or 65mg/m2 (UGT1A128 6/7) Drug: Raltitrexed 3mg/m2 q3w Radiation: radiotherapy in the use of intensity-modulated radiotherapy (IMRT) technology, the dose is judged according to the tumor site and radiotherapy purpose. Drug: rhIL-11 rhIL-11 50ug/kg, subcutaneous injection, qd

Arm

Intervention/Treatment

Experimental: rhTPO arm

rhTPO: 300 u/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal) Concurrent Chemoradiotherapy: Radiation: judged according to the tumor site and radiotherapy purpose. Irinotecan: 80 mg/m2 (UGT1A1*28 6/6) or 65 mg/m2 (UGT1A1*28 6/7) Raltitrexed: 3 mg/m2 q3w

Drug: rhTPO

rhTPO 300u/kg, subcutaneous injection, qd

Drug: irinotecan

80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)

Drug: Raltitrexed

3mg/m2 q3w

Radiation: radiotherapy

in the use of intensity-modulated radiotherapy (IMRT) technology, the dose is judged according to the tumor site and radiotherapy purpose.

Active Comparator: rhIL-11 arm

rhIL-11: 50 ug/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal) Concurrent Chemoradiotherapy: Radiation: judged according to the tumor site and radiotherapy purpose. Irinotecan: 80 mg/m2 (UGT1A1*28 6/6) or 65 mg/m2 (UGT1A1*28 6/7) Raltitrexed: 3 mg/m2 q3w

Drug: irinotecan

80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)

Drug: Raltitrexed

3mg/m2 q3w

Radiation: radiotherapy

in the use of intensity-modulated radiotherapy (IMRT) technology, the dose is judged according to the tumor site and radiotherapy purpose.

Drug: rhIL-11

rhIL-11 50ug/kg, subcutaneous injection, qd

Outcome Measures

Primary Outcome Measures

the rate of recovery of platelet accounts [From date of chemoradiation until the date of first documented recovery, assessed up to 6 months]
the duration after returning to normal [From date of first documented recovery until the date of first documented decrease of platelet accounts, assessed up to 6 months]

Secondary Outcome Measures

cycles of concurrent chemotherapy patients received during radiotherapy [through chemoradiation, an average of 5 weeks]
change of participant quality of life during treatment as assessed by EORTC-quality of life questionnaire-C30 [at the beginning and the end of chemoradiation.]
change of participant quality of life during treatment as assessed by EuroQol-5 dimensional (EQ-5D) questionnaire [at the beginning and the end of chemoradiation.]
the rate of pathological complete response. [Surgery scheduled 6-8 weeks after the end of chemoradiation]
pathological complete response (pCR) was defined no viable cancer cell under the examination of surgical resection specimen.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The primary tumor is colorectal cancer, histologically proved recurrence or metastasis disease, or pelvic relapse within 6 months after oxaliplatin-based adjuvant chemotherapy.
Not suitable for re-use of oxaliplatin and fluorouracil.
No medication history of irinotecan.
Lesions evaluable, and has indications for radiotherapy.
UGT1A1*28 gene phenotype is 6/6 or 6/7
Karnofsky physical condition score ≥ 70
Baseline platelet counts are 25-75×10^9/L, other bone marrow reserve and liver and kidney function meet the requirements of radiotherapy
Able to follow the program during the study period
Sign the informed consent

Exclusion Criteria:

Pregnant or breastfeeding women
Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ
If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance.
Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months
Organ transplantation requires immunosuppressive therapy
Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases
Subject blood routine and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g / L; absolute neutrophil count (ANC) ≥ 1.5 × 109 / L; Alanine transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal; alkaline phosphatase (ALP) ≤2.5 times the normal upper limit; serum total bilirubin <1.5 times the normal upper limit; serum creatinine <1 times the normal upper limit; serum albumin ≥ 30g / L
Anyone who is allergic to any research medication