Efficacy of oral administration of cystine and theanine in patients with colorectal cancer undergoing capecitabine-based adjuvant chemotherapy after surgery: study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled, phase II trial

IntroductionAlthough adjuvant capecitabine therapy for patients with colorectal cancer after surgery often causes adverse events (AEs), such as diarrhoea, stomatitis, anorexia and hand-foot syndrome (HFS), there are no standard prevention therapies. Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and are also expected to attenuate the AEs caused by capecitabine treatment. Therefore, our present study aimed to determine the safety and efficacy of cystine/theanine therapy in patients with colorectal cancer undergoing capecitabine-based adjuvant chemotherapy after surgery.Methods and analysisA multi-institutional, prospective, randomised, double-blinded, placebo-controlled, phase II trial is being planned. Patients with colorectal cancer treated with capecitabine as an adjuvant chemotherapy will be randomised into either the cystine/theanine group (n=50) or placebo group (n=50). Data will be collected during four courses of capecitabine therapy. The primary endpoint will be incidence rate of diarrhoea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints are incidence rates of other AEs (CTCAE v.4.0-JCOG), scores of the Japanese version of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire module for all patients with cancer (QLQ-C30) and for patients with colorectal cancer (QLQ-CR29), incidence rate of HFS according to the HFS grading scale, protocol adherence, completion rate of four courses of capecitabine therapy and the proportion of completion without delay or dose reduction, time to completion of four courses of capecitabine and total dose of capecitabine. A sample size of 100 patients will be analysed between November 2016 and April 2018.Ethics and disseminationEthical approval was obtained at all participating institutions. The results of this study will be submitted for publication in international peer-reviewed journals.Trial registration numberUMIN000024784; Pre-results.

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Efficacy of oral administration of cystine and theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery: a multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial (JORTC-CAM03)

Supportive Care in Cancer ◽

10.1007/s00520-019-05205-1 ◽

2019 ◽

Vol 28 (8) ◽

pp. 3649-3657 ◽

Cited By ~ 2

Author(s):

Reo Hamaguchi ◽

Takashi Tsuchiya ◽

Go Miyata ◽

Toshihiko Sato ◽

Kenichi Takahashi ◽

...

Keyword(s):

Colorectal Cancer ◽

Placebo Group ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Incidence Rate ◽

Incidence Rates ◽

Hand Foot Syndrome ◽

Grading Scale ◽

Colorectal Cancer Patients ◽

Double Blinded

Abstract Purpose Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery. Methods A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale. Results There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively). Conclusion This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS. Trial registration UMIN000024784

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A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.480 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 480-480

Author(s):

Carl Christoph Schimanski ◽

Stefan Kasper ◽

Susanna Hegewisch-Becker ◽

Jan Schroeder ◽

Friedrich Overkamp ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trial ◽

Phase Ii ◽

Cox Regression ◽

Phase Ii Trial ◽

Stage Iv ◽

High Recurrence Rate ◽

Muc1 Expression ◽

Double Blinded ◽

Clinical Trial Information

480 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513 . Clinical trial information: NCT01462513.

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Factors predicting the response to oral fluoropyrimidine drugs: A phase II trial on the individualization of postoperative adjuvant chemotherapy using oral fluorinated pyrimidines in stage III colorectal cancer treated by curative resection (ACT-01 Study)

Oncology Reports ◽

10.3892/or.2012.2177 ◽

2012 ◽

Vol 29 (2) ◽

pp. 437-444 ◽

Cited By ~ 3

Author(s):

TAKEO MORI ◽

MASAYUKI OHUE ◽

YASUMASA TAKII ◽

TADASHI HASHIZUME ◽

TOMOYUKI KATO ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Curative Resection ◽

Phase Ii Trial ◽

Stage Iii ◽

Postoperative Adjuvant Chemotherapy ◽

Oral Fluoropyrimidine ◽

Fluorinated Pyrimidines

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6089 POSTER Goshajinkigan (TJ-107) for Oxaliplatin-induced Sensory Neurotoxicity in Colorectal Cancer Patients – a Prospective, Randomized, Double-blinded, Placebo-controlled, Phase II Trial (GONE)

European Journal of Cancer ◽

10.1016/s0959-8049(11)71734-8 ◽

2011 ◽

Vol 47 ◽

pp. S418

Author(s):

T. Matsui ◽

T. Kono ◽

T. Hata ◽

M. Fukunaga ◽

Y. Munemoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Phase Ii ◽

Phase Ii Trial ◽

Colorectal Cancer Patients ◽

Double Blinded

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Randomized Placebo-Controlled Phase II Trial of Perifosine Plus Capecitabine As Second- or Third-Line Therapy in Patients With Metastatic Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.1980 ◽

2011 ◽

Vol 29 (33) ◽

pp. 4394-4400 ◽

Cited By ~ 69

Author(s):

Johanna C. Bendell ◽

John Nemunaitis ◽

Sasha J. Vukelja ◽

Christopher Hagenstad ◽

Luis T. Campos ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Complete Response ◽

Phase Iii ◽

Clinical Activity ◽

Double Blind ◽

Hand Foot Syndrome ◽

Previously Treated

Purpose In a multicenter, double-blind phase II trial, we compared the efficacy and safety of perifosine plus capecitabine (P-CAP) with placebo plus capecitabine (CAP) in patients with metastatic colorectal cancer (mCRC) who had progressed after as many as two prior therapies. Patients and Methods Patients (n = 38) not previously treated with capecitabine received P-CAP (perifosine 50 mg orally once daily, days 1 to 21 and CAP 825 mg/m2 orally twice daily, days 1 to 14) or CAP (825 mg/m2 orally twice daily, days 1 to 14) in 21-day cycles until disease progression. The primary end point was time to progression (TTP). Secondary end points included overall survival (OS), overall response rate (ORR), safety, and tolerability. Results Twenty patients were randomly assigned to P-CAP and 18 to CAP. Median TTP (27.5 v 10.1 weeks; P < .001) and median OS (17.7 v 7.6 months; P = .0052) were improved in patients receiving P-CAP versus CAP. ORR was 20% v 7% in the P-CAP and CAP groups, respectively, and one patient in the P-CAP group had a complete response. A subset analysis of fluorouracil-refractory patients showed a median TTP of 17.6 v 9.0 weeks (P < .001) and median OS of 15.1 v 6.5 months (P = .0061). Toxicities, including diarrhea, nausea, fatigue, and hand-foot syndrome, were manageable. Conclusion P-CAP showed promising clinical activity compared with CAP in previously treated patients with mCRC. A phase III trial is underway comparing P-CAP with CAP in patients with refractory mCRC.

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A randomized, double-blinded, placebo-controlled multicenter phase II trial of adjuvant immunotherapy with tecemotide (L-BLP25) after R0/R1 hepatic colorectal cancer metastasectomy (LICC): Final results.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3537 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3537-3537

Author(s):

Carl Christoph Schimanski ◽

Stefan Kasper ◽

Susanna Hegewisch-Becker ◽

Jan Schroeder ◽

Friedrich Overkamp ◽

...

Keyword(s):

Colorectal Cancer ◽

Phase Ii ◽

Cox Regression ◽

Phase Ii Trial ◽

Stage Iv ◽

High Recurrence Rate ◽

R0 Resection ◽

Muc1 Expression ◽

Mucin 1 ◽

Double Blinded

3537 Background: Hepatic metastasectomy is the only potential curative treatment option for stage IV colorectal cancer (CRC) limited to liver metastases (LM). After R0 resection of LM the high recurrence rate remains a major challenge. L-BLP25 is an antigen-specific cancer vaccine targeting mucin 1 (MUC1). The LICC trial aimed to improve survival outcome in mCRC patients (pts) after R0/R1 LM resection. Methods: This LICC trial, a binational, multicenter, double-blinded, placebo controlled phase II trial, included pts with stage IV LM limited CRC after resection of primary tumor and LM (R0/R1) within the last 8 weeks, ECOG 0/1 and adequate organ function. Pts were 2:1 randomized to receive L-BLP25 or placebo. L-BLP25 930 µg was administered as 8 weekly subcutaneous doses followed by 6 week maintenance intervals until recurrence or a maximum of 2 years. Cyclophosphamide 300 mg/m2 (CP) or matching saline (NS) was given intravenously 3 days prior to first L-BLP25/placebo. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS), secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. Differences in RFS and OS were analyzed with exploratory log-rank tests on the intention-to-treat population. Results: Of 121 pts enrolled between Oct 2011 and Dec 2014, 79 pts received L-BLP25+CP, 42 placebo+NS. Baseline characteristics were well balanced. Median age was 60 years. Median RFS was 6.1 (90% CI: 5.8-8.8) vs. 11.4 months (90% CI: 5.0-20.3) and estimated 3-year OS rate 69.1% vs. 79.1% for L-BLP25 and placebo, respectively. Two-factorial Cox regression models showed no impact of MUC1 expression or treatment on RFS or OS. The most common L-BLP25-related grade 3/4 adverse events were diarrhea, anemia and back pain. There was one death in the L-BLP25 arm due to Merkel cell carcinoma assessed by the investigator as being potentially related to vaccination. Conclusions: The LICC trial failed to meet its primary endpoint of significantly improving RFS and OS with L-BLP25. MUC1 expression was not associated with outcome. Clinical trial information: NCT01462513.

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