Clinical trial NCT01993472: Study of Andrographolides With or Without Capecitabine to Treat Colorectal Cancer
Official title: Andrographolides With or Without Capecitabine for Elderly Patients With Locally Advanced or Recurrent or Metastasis Inoperable Colorectal Cancer: a Randomized, Open-label Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2013-11-25
Enrollment: 308
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy and safety of Andrographolides combined with Capecitabine in treatment of elderly patients with locally advanced or recurrent or metastasis inoperable colorectal cancer


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum
2. Locally advanced or recurrent or metastasis inoperable disease
3. At least 1 measurable or non-measurable lesion per RECIST version 1.1 guidelines. Lesion must not be chosen from a previously irradiated field unless there had been documented tumor progression in that lesion prior to randomization. All sites of disease must be evaluated ≤ 28 days prior to randomization.
4. Man or woman ≥ 65 years of age
5. Hematological function, as follow: (≤ 10 days prior to randomization)

   * Absolute neutrophil count (ANC) ≥ 1.5×109/L
   * Platelet count ≥ 75×109/L
   * Hemoglobin ≥ 8.0 g/dL
6. Renal function, as follows: (≤ 10 days prior to randomization)

   * Creatinine≤ 1.5×ULN
7. Hepatic function, as follow: (≤ 10 days prior to randomization)

   * Aspartate aminotransferase (AST) ≤ 3×ULN(if liver metastases≤ 5×ULN )
   * Alanine aminotransferase (ALT) ≤ 3×ULN(if liver metastases≤ 5×ULN )
   * Total bilirubin≤ 1.5×ULN
8. Subject or subject's legally acceptable representative has provided informed consent

Exclusion Criteria:

1. Symptomatic brain metastases requiring treatment
2. History of other malignancy, except:

   * Malignancy treated with curative intent and with no known active disease present for ≥ 5 years prior to randomization and felt to be at low risk for recurrence by the treating physician
   * Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
   * Adequately treated cervical carcinoma in situ without evidence of disease
   * Prostatic intraepithelial neoplasia without evidence of prostate cancer
3. Antitumor therapy(eg, chemotherapy, hormonal therapy, immunotherapy, antibody therapy) ≤ 21 days before randomization. Subjects must have recovered from any acute radiotherapy-related toxicity
4. Radiotherapy≤ 14 days before randomization. Subjects must have recovered from any acute radiotherapy-related toxicities
5. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia)≤ 6 months prior to randomization
6. History of interstitial lung disease(ILD) eg, interstitial pneumonitis, pulmonary fibrosis or evidence of ILD on baseline chest CT or MRI
7. History of any medical or psychiatric condition or labortory abnomality that in the opinion of the investigator may increase the risk associated with the study participation or investigational product administration or may interfere with the interpretation of the results
8. Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolic event ≤ 30 days before randomization. If on anticoagulation, subject must be on stable therapeutic dose prior to rangdomization.
9. Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures or is unwilling or unable to comply with study requirements

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: From date of randomization until the date of first documented progression，assessed up to 100 months
Secondary outcomes:
measure: overall survival
timeFrame: From date of randomization until the date of death from any cause，assessed up to 100 months
measure: Response Rate
timeFrame: From date of randomization until the date of first documented partial response or complete response, assessed up to 100 months
measure: Quality of Life
timeFrame: From date of randomization until the date of death from any cause，assessed up to 100 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: the First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
References:
citation: Bruchard M, Mignot G, Derangere V, Chalmin F, Chevriaux A, Vegran F, Boireau W, Simon B, Ryffel B, Connat JL, Kanellopoulos J, Martin F, Rebe C, Apetoh L, Ghiringhelli F. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med. 2013 Jan;19(1):57-64. doi: 10.1038/nm.2999. Epub 2012 Dec 2.