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

Phase 2

• Conditions: Thrombopenia; Recurrent Colorectal Carcinoma
• Interventions: Drug: rhTPO; Drug: irinotecan; Drug: Raltitrexed; Radiation: radiotherapy; Drug: rhIL-11

• Registration Number: NCT03823079
• Lead Sponsor: Fudan University

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.

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 Timeline

• Status Verified: 2019-01
• Study First Submitted: 2019-01-19
• Study First Submitted QC: 2019-01-28
• Last Update Submitted: 2019-01-28
• Study First Posted: 2019-01-30
• Last Update Posted: 2019-01-30
• Study Start: 2019-02-01
• Primary Completion: 2019-09-01
• Study Completion: 2020-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rhTPO arm	radiotherapy	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
rhTPO arm	rhTPO	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
rhIL-11 arm	radiotherapy	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
rhIL-11 arm	rhIL-11	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
rhIL-11 arm	irinotecan	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
rhTPO arm	Raltitrexed	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
rhTPO arm	irinotecan	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
rhIL-11 arm	Raltitrexed	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

Primary Outcome Measures

Name	Time	Method
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
the rate of recovery of platelet accounts	From date of chemoradiation until the date of first documented recovery, assessed up to 6 months

Secondary Outcome Measures

Name	Time	Method
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.
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.