Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03255434
Other study ID # ICM-URC2016/27
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date November 1, 2017
Est. completion date December 2024

Study information

Verified date June 2023
Source Institut du Cancer de Montpellier - Val d'Aurelle
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not adjusted to the body proportions of lean and fat (i.e. body composition) of individual patients. Patients with low muscle mass behave like patients "overdosed" with chemotherapy resulted in dose-limiting toxicities (e.g. dose reductions, treatment delays or permanent treatment discontinuation), independently of the patient's weight.


Description:

Adjuvant chemotherapy with fluoropyrimidines and Oxaliplatin is the current worldwide standard of care for stage III colorectal cancer (CRC). This regimen leads to significant cost, toxicity, and patient inconvenience. Oxaliplatin induces two distinct forms of neuropathy: a common acute syndrome that is transient (dysesthesia, contractures and numbness) and a dose-limiting chronic sensory neurotoxicity that is cumulative. Neurotoxicity is common; it affects 80% of patients and becomes chronic in 15-20% of cases, sometimes irreversibly. Chronic neurotoxicity can severely affect everyday life activities. To date, neuromodulators agents have failed to prevent neurotoxicity and Stop & Go strategies, intended to decrease the cumulative dose of Oxaliplatin administrated, are more appropriate for palliative treatment of advanced CRC. Recent data support the plausibility of a shorter duration of adjuvant treatment without loss of efficacy. This hypothesis is tested in several international trials. Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not adjusted to the body proportions of lean and fat (i.e. body composition) of individual patients. The impact of body composition on drug metabolism is however well known: i.e. anesthetics accumulate in adipose tissue and specific precautions are essential to avoid overdose. Concerning chemotherapies, the lean body mass (LBM) may be the salient feature defining drug metabolism. A theme is emerging from recent studies: in patients with breast cancer and treated with 5-FU (whose dosage was calculated from the body surface), severe depletion of the LBM is a powerful predictor of excessive toxicity. Indeed, depletion of the LBM, as precisely defined by computed tomography, is a unique predictor of clinically unacceptable toxicity. Low LBM was shown to be a significant predictor of dose-limiting toxicity (DLT) in CRC patients administered 5-FU using a conventional BSA-based dosing and DLT was concentrated in patients receiving >20 mg 5FU/kg LBM. Two cohorts of CRC patients treated with Oxaliplatin showed that overall DLTs, and specifically Oxaliplatin-due neuropathy, occurred mostly in patients who receive > 3.09 mg/Oxaliplatin/kg LBM. Although, preliminary findings are available in hepatocellular carcinoma, the area under the concentration time curve (AUC) of Sorafenib cancer therapy was doubled in patients with depleted LBM (102.4 vs. 53.7ng/mL.h), which seem of interest. Patients with low muscle mass behave like patients "overdosed" with chemotherapy resulted in dose-limiting toxicities (e.g. dose reductions, treatment delays or permanent treatment discontinuation), independently of the patient's weight.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 160
Est. completion date December 2024
Est. primary completion date July 28, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: - Age: more than 18 years old up to 75 years old including. Histologically confirmed adenocarcinoma of the colon. - Has undergone a curative resection for stage III colon cancer. - Scheduled to receive 6 months of Oxaliplatin-based adjuvant chemotherapy at a dose of 85 mg/m² of Oxaliplatin every 2 weeks (simplified FOLFOX 4 regimen). - The following laboratory values obtained = 28 days prior to inclusion: WBC = 3000/mm3; ANC =1500/mm3; PLT =100,000/mm3; HgB =10.0g/dl; Total bilirubin =1.5 x upper normal limit (UNL); Serum creatinine =1.5 x UNL; Serum calcium = 1.2 x UNL; Serum magnesium = 1.2 x UNL. - Central venous access line present or patient scheduled to have a central line placed prior to starting chemotherapy or the treatment protocol. - Negative pregnancy test (serum or urine) done = 7 days prior to registration, for women of childbearing potential only. - Ability to complete questionnaire(s) by themselves or with assistance. - ECOG Performance Status (PS) of 0, 1 for patients until 70 years old included and ECOG PS of 0 for patients between 70 to 75 years old included. - Has provided informed written consent. - Patient willing to provide blood sample for research purposes - Patient affiliated to a French social security system Exclusion Criteria: - Pregnant or breastfeeding women - Men or women of childbearing potential who are unwilling to employ adequate contraception since this study involves agents that have known genotoxic, mutagenic and teratogenic effects - Pre-existing peripheral neuropathy of any grade. - Prior treatment with neurotoxic chemotherapy such as Oxaliplatin, cisplatin, taxanes, or vinca alkaloids. - Treatment with 1) the anticonvulsants carbamazepine (e.g., Tegretol®), phenytoin (e.g., Dilantin®), valproic acid (e.g. Depakine®), gabapentin (Neurontin®); pregabalin (Lyrica®); 2) the following neurotropic agents: venlafaxine (Effexor®), desvenlafaxine (Pristiq®), milnacipran (Savella®) or duloxetine (Cymbalta®); 3) Tricyclic antidepressants (such as amitryptilline) or 4) any other agent specifically given to prevent or treat neuropathy. - Family history of a genetic/familial neuropathy. - Participation in another medication trial within 30 days prior to study entry - Legal incapacity or physical, psychological social or geographical status interfering with the patient's ability to sign the informed consent or to terminate the study - History of other solid tumor in 3 years before the inclusion, excepted of cancer in situ of the cervix and skin cancer (basal or squamous cell) treated and controlled.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Oxaliplatin
Simplified FOLFOX 4 regimen: Association of Oxaliplatin (85 mg/m² ) + simplified LV5FU2 Length of a cycle : 2 days Interval between 2 cycles : 2 weeks (D1=D15) Expected number of cycles: 12
Oxaliplatin LBM
Simplified FOLFOX 4 regimen: Association of Oxaliplatin (LBM) + simplified LV5FU2

Locations

Country Name City State
France Centre François Baclesse Caen
France CHU La TIMONE Marseille
France Hôpital Européen Marseille Bouches Du Rhône
France Centre hospitalier régional et universitaire de Montpellier Montpellier Hérault
France Institut regional du Cancer - Val d Aurelle Montpellier
France AP-HP Hôpital Saint-Louis Paris
France Hôpital Saint-Jean Perpignan Pyrénées-orientales
France Centre Eugène Marquis Rennes
France Centre Paul Strauss Strasbourg
France CHU de Nancy Vandœuvre-lès-Nancy Lorraine
France Insitut de Cancérologie de Lorraine Vandœuvre-lès-Nancy Meurthe-et-Moselle,

Sponsors (1)

Lead Sponsor Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Evaluation of neurotoxicity associated with Oxaliplatin Neurotoxicity assessment through study completion, an average of 5 years
See also
  Status Clinical Trial Phase
Completed NCT00025337 - Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated Phase 3
Active, not recruiting NCT04164069 - Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab Phase 1
Not yet recruiting NCT05870800 - Neoadjuvant Chemoimmunotherapy for Resectable Non-Metastatic Proficient Mismatch Repair (PMMR) Colon Cancer Phase 2
Recruiting NCT02280278 - Cytokine-induced Killer Cell Immunotherapy for Surgical Resected Stage III Colorectal Cancer Patients After Chemotherapy Phase 3
Completed NCT01191684 - Vaccine Therapy in Treating Patients With Colorectal, Stomach, or Pancreatic Cancer Phase 1
Completed NCT00551421 - Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer Phase 1/Phase 2
Recruiting NCT03958435 - Real-world Retrospective Data Analysis of Adjuvant Therapy for Patients With Stage II-III Colon Cancer After Radical Surgery
Completed NCT01890213 - Immunotherapy With CEA(6D) VRP Vaccine (AVX701) in Patients With Stage III Colorectal Cancer Phase 1
Completed NCT00028496 - Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer Phase 1
Completed NCT01126346 - Quality of Life and Survivorship Care in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy (HIPEC) N/A
Terminated NCT00087191 - EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer N/A
Completed NCT00003835 - Combination Chemotherapy in Treating Patients With Stage III Colon Cancer Phase 3
Recruiting NCT05062889 - Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment Resected Colon Cancer Patients Phase 2
Recruiting NCT04416490 - Oxaliplatin Adjuvant Chemotherapy After Curative Resection of Primary Colon Cancer
Active, not recruiting NCT02836977 - Maintenance Tegafur-uracil Versus Observation Following Adjuvant Oxaliplatin-based Regimen in Patients With Stage III Colon Cancer After Radical Resection N/A
Completed NCT00005818 - SU5416 and Irinotecan in Treating Patients With Advanced Colorectal Cancer Phase 1/Phase 2
Completed NCT00019006 - Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer Phase 1
Recruiting NCT05174169 - Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease Phase 2/Phase 3
Not yet recruiting NCT06287814 - French Assessment of MRD by Liquid Biopsies in Stage III CRC Patients (FRENCH.MRD.CRC)
Terminated NCT01606124 - Polyphenon E in Treating Patients With High-Risk of Colorectal Cancer Phase 2