Sorafenib Plus Capecitabine Efficacy Assessment in Patients With Advanced Pre-treated Colorectal Cancer

NCT01290926 | Completed Phase 2

• 1 other identifier: EudraCT 2010-023695-91
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 7

Brief Summary

Prospective non-randomized phase II study assessing the activity of the Capecitabine-Sorafenib combination by estimating overall survival of the study population at a fixed time point (6 months) and, as an exploratory analysis the overall survival of metabolic responders versus non-responders.

Conditions

Colorectal Cancer

Keywords

advanced chemorefractory colorectal cancer; sorafenib; capecitabine; FDG-PET; early metabolic response

Outcome Measures

Primary Outcomes (1)

• Overall survival at 6 months fixed endpoint

  The 2 primary co-endpoints are : 1. To obtain a preliminary assessment about the activity of the combination by estimating overall survival of the study population at a fixed time point (6 months) 2. To compare as an exploratory analysis the overall survival of metabolic responders versus non-responders.

  6 months

Secondary Outcomes (5)

• To estimate the Progression Free Survival (PFS) distribution of the study population

  12 months

• To determine the objective response rate of the study population as assessed by standard imaging

  12 months

• To describe the adverse reactions associated with the study regimen in the study population.

  12 months

• To determine the correlation of early metabolic response, as assessed by FDG-PET/CT immediately before the first and the second cycles of treatment with the study regimen, with overall survival, progression-free survival, and response.

  12 months

• To determine the correlation of growth modulation index (GMI), defined as the time to progression under the study regimen over the time to progression un-der the latest prior regimen administered to the patient, with overall survival and progression-free

  12 months

Study Arms (1)

Capecitabine & Sorafenib

EXPERIMENTAL

Sorafenib 200mg in the morning,400mg in the evening; escalation to 400mg twice daily after 1 cycle, Oral, Continuous dosing Capecitabine 850mg/m2 twice daily, Oral Days 1-14, weeks 1-2

Drug: chemotherapy

Interventions

chemotherapy DRUG

sorafenib 600mg/day capecitabine 1250 mg/m²/day

Also known as: Xeloda, Nexavar

Capecitabine & Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed colorectal cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• All standard chemotherapy agents (fluoropyrimidines, irinotecan, and oxaliplatin) and monoclonal antibodies (bevacizumab, cetuximab, and panitumumab) are allowed as administered therapy before study entry. No more than two lines of treatment for metastatic or recurrent disease are allowed, except for patients with KRAS-wt tumors, for which third line with anti-EGFR agents is allowed.
• Age over 18 years.
• Life expectancy of greater than 12 weeks.
• ECOG performance status ≤ 1.
• Participants must have normal organ and marrow function as defined below:
• Leukocytes \> 3,000/mcL
• Absolute neutrophil count \> 1,500/mcL
• Platelets \> 100,000/mcL
• total bilirubin within 2 × normal institutional limits
• AST/ALT/PAKL levels \< 5 × institutional upper limit of normal
• creatinine within 2 × normal institutional limits or creatinine clearance \> 35mL/min
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants may not be receiving any other experimental agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib or capecitabine.
• Bleeding diathesis, history of cardiovascular ischemic disease or cerebrovascular incident within the last six months, or major surgery within four weeks.
• Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because sorafenib and capecitabine are antitumor agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with sorafenib or capecitabine, breastfeeding should be discontinued if the mother is treated with sorafenib or capecitabine. These potential risks may also apply to other agents used in this study.
• Uncontrolled Diabetes
• FDG PET/CT negative lesions or non metabolically assessable lesions (to small \<2cm) at the base line FDG PET/CT
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Erasme University Hospital: collaborator
• INDC Entité Jolimontoise: collaborator
• Centre Hospitalier Chretien: collaborator
• Universiteit Antwerpen: collaborator
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator
• Hospital Ambroise Paré Paris: collaborator

Study Sites (7)

Universiteit Ziekenhuis Antwerpen

Antwerp, Antwerpen, Belgium

Location

Cliniques Universitaires Saint Luc

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Hopital Erasme

Brussels, 1070, Belgium

Location

Entité Jolimontoise

La Louvière, Belgium

Location

Hopitaux St Joseph

Liège, 4000, Belgium

Location

CHU Ambroise Paré

Mons, 7000, Belgium

Location

Related Publications (2)

• Charette N, Vandeputte C, Ameye L, Bogaert CV, Krygier J, Guiot T, Deleporte A, Delaunoit T, Geboes K, Van Laethem JL, Peeters M, Demolin G, Holbrechts S, Flamen P, Paesmans M, Hendlisz A. Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials. BMC Cancer. 2019 Feb 12;19(1):134. doi: 10.1186/s12885-019-5319-8.

  PMID: 30744591 DERIVED

• Hendlisz A, Deleporte A, Delaunoit T, Marechal R, Peeters M, Holbrechts S, Van den Eynde M, Houbiers G, Filleul B, Van Laethem JL, Ceyssens S, Barbuto AM, Lhommel R, Demolin G, Garcia C, El Mansy H, Ameye L, Moreau M, Guiot T, Paesmans M, Piccart M, Flamen P. The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer. PLoS One. 2015 Sep 30;10(9):e0138341. doi: 10.1371/journal.pone.0138341. eCollection 2015.

  PMID: 26421426 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drug Therapy; Capecitabine; Sorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Alain Hendlisz, MD

  Jules Bordet Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2011
• First Posted: February 7, 2011
• Study Start: February 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: February 24, 2016

Record last verified: 2016-02

Locations

BE (7)