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Completed

NCT Number: NCT01718873

Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer

The purpose of this study is to evaluate if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Rectal Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, Italy

About this study

OBELICS is a two-arm phase 3 trial comparing in mCRC patients (1:1): concurrent administration of bevacizumab in combination with modified FOLFOX-6 regimen (mFOLFOX-6) or modified OXXEL regimen (mOXXEL), in which bevacizumab is administered the same day as oxaliplatin, (standard arm); and sequential administration of bevacizumab with the same chemotherapeutic regimens, in which bevacizumab is administered 4 days before oxaliplatin at each cycle (experimental arm) Oxaliplatin regimen (mFOLFOX/mOXXEL) is chosen according to local clinical practice at the beginning of the study.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histological diagnosis of colorectal adenoma carcinoma
  • Stage IV disease
  • Presence of at least one measurable target lesion (according to RECIST), and not previously radiated.
  • Age ≥ 18 e ≤ 75 years
  • ECOG Performance status 0-1
  • Life expectancy >3 months
  • Adequate recovery from surgery, with at least 28 days from surgery to date of pre-study biopsy.
  • Adequate contraception for male and female patients of child bearing potential
  • informed consent

Exclusion criteria

  • More than one previous line of therapy for metastatic disease
  • Prior treatment with bevacizumab or oxaliplatin (previous treatment with irinotecan,, cetuximab, fluoropyrimidine, folic acid are permitted)
  • Primary tumor that is stenosing and/or that infiltrates the entire thickness of the intestinal wall
  • Regular use of NSAIDs or aspirin
  • Bleeding disorders or coagulopathy
  • Concurrent anticoagulant therapy
  • Suspected or cerebral metastases (to verify in the presence of symptoms)
  • Neutrophils < 2000 / mm3, platelets < 100,000 / mm3, hemoglobin < 9g/dl
  • Creatinine > 1.5 times the upper normal limit
  • GOT and/or GPT > 2.5 times the upper normal limit, bilirubin > 1.5 times the upper normal limit in absence of liver metastases
  • GOT and/or GPT > 5 times the upper normal limit, bilirubin > 3 times the upper normal limit in presence of liver metastases
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
  • Congestive heart failure, ischemic coronary events within past 12 months, uncontrolled cardiac arrhythmia
  • Uncontrolled hypertension
  • Active or uncontrolled infection
  • Any concomitant condition that, in the investigator's opinion, would contraindicate the use of any of the study drugs
  • Pregnancy or lactation
  • Central nervous system disorders or peripheral neuropathy > grade 1 (CTCAE v. 4.0)
  • Inability to comply with follow up procedures of the study

Treatment and study plan

Bevacizumab

Drug

5 mg/kg every 2 weeks for up to 24 weeks. After 24 weeks, those patients without disease progression will receive bevacizumab 7.5 mg/kg every 3 weeks until progression of disease or unacceptable toxicity.

Other names: Avastin

Oxaliplatin

Drug

85mg/m2 IV every 2 weeks for up to 24 weeks

Other names: Eloxatin

levo-folinic acid

Drug

200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks

Other names: Lederfolin

5-fluorouracil

Drug

400 mg/m2 IV bolus followed by 2400 mg/m2 IV infusion over 46 hours, every 2 weeks for up to 24 weeks (given in mFOLFOX-6 schedule)

Other names: Fluorouracil

Capecitabine

Drug

1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)

Other names: Xeloda

Primary outcomes

  1. Objective Response Rate

    Time frame: Objective response was assessed by computed tomographic scan or other appropriate imaging at weeks 12 and 24 from randomization, and every 3 months thereafter, assessed up to 90 months.

    Objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, was the primary end point and was defined as the number of complete plus partial responses divided by the number of enrolled patients.

    Per RECIST v 1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary outcomes

  1. Disease Control Rate

    Time frame: At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months

    Disease control rate was calculated by adding complete and partial responses and stable disease.

  2. Overall Survival

    Time frame: assessed up to 90 months

    Overall survival was defined as the time from randomization to the date of death. Patients alive at the time of the final analysis were censored on the date of the last follow-up information available.

  3. Progression-free Survival (PFS)

    Time frame: assessed up to 90 months

    Progression-free survival was defined as the time from randomization to the date of progression or death, whichever occurred first. Patients without progression were censored on the date of the last follow-up visit.

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  4. Toxic Effects

    Time frame: up to 4 weeks after the end of the treatment

    Toxic effects were scored according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. For the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 scale score range from 1 to 4. A high score, that is 3 and 4, represents a high level of toxicity, whereas the minimum values, that is 1 and 2, represents a mild/modest level of toxicity.

Sponsors and collaborators

Lead sponsor

National Cancer Institute, Naples

Other

Registry information

Official study title

Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer

Acronym: OBELICS

Important dates

Study start
2012
Primary completion
2015
Study completion
2019
First posted
Oct 31, 2012
Registry last updated
Apr 12, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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