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LEAn Body Mass Normalization of OXaliplatin Based Chemotherapy (LEANOX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03255434
Recruitment Status : Recruiting
First Posted : August 21, 2017
Last Update Posted : August 31, 2017
Sponsor:
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief 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.

Condition or disease Intervention/treatment Phase
Stage III Colon Cancer Drug: Oxaliplatin Drug: Oxaliplatin LBM Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: LEAn Body Mass Normalization of OXaliplatin Based Chemotherapy for Stage III Colon Cancer Patients Treated in Adjuvant Setting: Impact on Oxaliplatin-induced Sensitive Neurotoxicity. A Multicenter Phase II Randomized Trial (LEANOX)
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin

Arm Intervention/treatment
Active Comparator: Folfox 4
Standard FOLFOX4: Oxaliplatin and simplified LV5FU2 Dose of oxaliplatin 85mg/m²
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

Experimental: Folfox 4 LBM
Adapted FOLFOX4: Oxaliplatin and simplified LV5FU2 Dose of oxaliplatin allocated according to lean body mass (LBM)
Drug: Oxaliplatin LBM
Simplified FOLFOX 4 regimen: Association of Oxaliplatin (LBM) + simplified LV5FU2




Primary Outcome Measures :
  1. Evaluation of neurotoxicity associated with Oxaliplatin [ Time Frame: through study completion, an average of 5 years ]
    Neurotoxicity assessment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03255434


Contacts
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Contact: eric ASSENAT +33467603102 eric.assenat@chu-montpellier.fr

Locations
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France
Institut regional du Cancer - Val d Aurelle Recruiting
Montpellier, France, 34298
Contact: Bleuse Jean Pierre    +33467612344    jean-pierre.bleuse@icm.unicancer.fr   
Principal Investigator: assenat eric         
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Investigators
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Study Director: marc YCHOU Institut régional du Cancer de Montpellier

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Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT03255434    
Other Study ID Numbers: ICM-URC2016/27
First Posted: August 21, 2017    Key Record Dates
Last Update Posted: August 31, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Oxaliplatin
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Antineoplastic Agents