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Colorectal NeoplasmsPhase 3NCT00973609

Optimal Maintenance Therapy With Bevacizumab After Induction in Metastatic Colorectal Cancer (CRC)

A Phase 3 study testing 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab in people with Colorectal Neoplasms, run by AIO-Studien-gGmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Investigating the efficacy of maintenance and reinduction treatment or no treatment and watchful waiting in subjects with inoperable or irresectable and non-progressive metastatic colorectal cancer after first line induction treatment for 24 weeks with a fluoropyrimidine-, oxaliplatin- and bevacizumab-based… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
853 participants
Where
1 siteGermany
Study dates
Aug 2009to Aug 2015
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed and inoperable or irresectable metastatic colorectal cancer (stage IV)
  • Measurable lesion according to RECIST measured within 4 weeks prior to registration of the subject for the study
  • Not allowed prior treatments:
  • Previous chemotherapy for metastatic disease (adjuvant therapy for non-metastasized disease is allowed if terminated more than 6 months ago and without recurrence within 6 months after the end of adjuvant treatment)
  • Prior radiation of indicator lesion(s), except for documented progression during radiation and termination of radiotherapy at least 4 weeks prior to entry into the study
  • 18 and over
Show all 44Show fewer
  • ECOG 0-2
  • Prior and concomitant associated diseases:
  • No past or current history of malignancies except for the indication under this study and curatively treated:
  • Basal and squamous cell carcinoma of the skin
  • in situ carcinoma of the cervix
  • Other malignant disease without recurrence after at least 5 years of follow-up
  • No severe internal disease (insufficiently treated or uncontrolled arterial hypertension, haemoptoe, New York Heart Association (NYHA) grade II or greater congestive heart failure, symptomatic coronary heart disease, myocardial infarction (= < 12 months prior to inclusion), serious cardiac arrhythmia requiring medication, peripheral arterial occlusive disease stage II or greater, uncontrolled severe disease)
  • No history or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumour, seizure not controlled with standard medical therapy, brain metastases or history of stroke).
  • No pre-existing neuropathy > = grade 1 (NCI CTCAE), except for loss of tendon reflex as the only symptom
  • No interstitial pneumonia or symptomatic fibrosis of the lung
  • No allogenic transplantation requiring immuno-suppressive therapy
  • No severe non-healing wounds, ulcers or bone fractions.
  • No thrombosis or severe bleeding within 6 months prior to entry into the study (except for bleeding of the tumor before its surgical resection) and no evidence of bleeding diathesis or coagulopathy.
  • Laboratory requirements - within 7 days prior to enrollment:
  • Neutrophil count > = 1,500/μl
  • Platelets > = 100,000/μl
  • Hb > = 9g/dl dL (may be transfused to maintain or exceed this level)
  • Serum creatinine clearance > 50ml/min (Cockroft/Gault)
  • Serum total bilirubin: = < 1.5 x UNL
  • AST and ALT = < 2.5 x UNL; = < 5 x UNL in subjects with documented liver metastases
  • Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.
  • Laboratory requirements in fertile women, within 2 days prior to treatment: Negative serum pregnancy test
  • Other medication:
  • No concomitant therapy with certain anti-viral medicines (sorivudine and brivudine or analogue compounds).
  • No continuous medication with ASS > 325 mg or NSAIDs, known to inhibit platelet function.
  • Other:
  • No major surgical procedure, open biopsy, nor significant traumatic injury within 28 days prior to study treatment start, nor anticipation of the need for major surgical procedure during the course of the study except for surgery for colorectal cancer with curative intent and central venous line placement for chemotherapy administration, which must be inserted at least 2 days prior to treatment start.
  • No pregnancy or breastfeeding women.
  • No women of child-bearing potential with positive or missing pregnancy test at study entry; post-menopausal women must have been amenorrheic for at least 12 months to be considered of non-child-bearing potential.
  • No sexually active men or women of childbearing potential not willing to use effective means of contraception (intrauterine contraceptive device, implants, injectables, sexual abstinence or vasectomised partner).
  • No subjects with known allergy to the used study drugs or to any of its excipients.
  • No known DPD deficiency.
  • No proteinuria (>1+); if dipstick test of urine exceeds 1+, proteinuria has to be below 1g protein in 24 hours urine.
  • No concomitant treatment with preparations of St. John's wort.
  • No currently or recent (within the 28 days prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
  • No known grade III/IV allergic reaction against monoclonal antibodies.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the subject before registration in the trial.
  • Before subject registration, written informed consent must be given according to ICH/GCP, and national/local regulations. The subject must be competent to comprehend, sign, and date an IEC-approved informed consent form.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • AIO-Studien gGmbH

    Berlin, State of Berlin, 10623

Other trials in Germany

About this study

Official title: Randomized Three Arm Phase III Trial on Induction Treatment With a Fluoropyrimidine-, Oxaliplatin- and Bevacizumab-based Chemotherapy for 24 Weeks Followed by Maintenance Treatment With a Fluoropyrimidine and Bevacizumab vs. Bevacizumab Alone vs. no Maintenance Treatment and Reinduction in Case of Progression for First-line Treatment of Patients With Metastatic Colorectal Cancer

Investigating the efficacy of maintenance and reinduction treatment or no treatment and watchful waiting in subjects with inoperable or irresectable and non-progressive metastatic colorectal cancer after first line induction treatment for 24 weeks with a fluoropyrimidine-, oxaliplatin- and bevacizumab-based chemotherapy.

The maintenance treatment with capecitabine or 5-FU/folinic acid and bevacizumab will be compared with a maintenance treatment with bevacizumab alone or no maintenance treatment. Reinduction treatment will be done in case of progression.

Read the detailed description

Chemotherapy and bevacizumab represent a standard of care in treatment of metastatic colorectal cancer. Until now, continuation of chemotherapy - and bevacizumab - represents the standard of care in colorectal cancer treatment. However, since the OPTIMOX1 trial showed an equivalent duration of disease control for a de-escalation / maintenance / reintroduction strategy compared with a treatment until progression strategy for oxaliplatin-based chemotherapy, the question is whether this strategy might apply also to bevacizumab in combination with chemotherapy. Furthermore, with the introduction of bevacizumab, there are new options for a maintenance treatment which should be evaluated.

As the continuation of chemotherapy plus bevacizumab until disease progression has to be regarded as standard of care, the question is whether a de-escalation of treatment intensity or even withdrawal of treatment ("drug holiday") after a certain treatment period will not be inferior with respect to resulting time with tumor control, but allow patients a period with less toxicity and gain of quality of life.

Being tested
5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab
Keywords
metastatic colorectal cancer, Bevacizumab, Avastin®, phase 3, maintenance treatment, treatment pause, drug holiday, stage IV
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5-Fluorouracil, Folic acid, Capecitabine; BevacizumabDrug

    Induction (and reinduction) treatment regimen for 24 weeks: Fluoropyrimidine, oxaliplatin and bevacizumab.

    Following induction treatment regimen (for maintenance treatment): No maintenance treatment.

  • 5-Fluorouracil, Folic acid, Capecitabine; BevacizumabDrug

    Induction (and reinduction) treatment regimen for 24 weeks: Fluoropyrimidine, oxaliplatin and bevacizumab.

    Following induction treatment regimen (for maintenance treatment): Fluoropyrimidine + Bevacizumab.

  • 5-Fluorouracil, Folic acid, Capecitabine; BevacizumabDrug

    Induction (and reinduction) treatment regimen for 24 weeks: Fluoropyrimidine, oxaliplatin and bevacizumab.

    Following induction treatment regimen (for maintenance treatment): Bevacizumab monotherapy.

Study groups in NCT00973609
Study groupRoleWhat they receive
Fluoropyrimidine + BevacizumabActive comparatorStandard therapy
Receives: Drug: 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab
Bevacizumab monotherapyExperimentalNot described
Receives: Drug: 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab
No maintenance treatmentExperimentalNot described
Receives: Drug: 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to failure of maintenance and reinduction treatment strategy measured from randomization

    Measured: From randomization until second progression after reinduction treatment

Secondary outcomes (1)

  1. TFS, Toxicity, QoL, PFS 1, PFS 2, ORR (first induction), ORR (reind. treatm.), Treatment free interval/duration of maintenance therapy, second. Resection rate, Reasons for discontinuation, OS, Translational research.

    Measured: From enrollment until second progression after reinduction treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2009 (estimated)
  2. Study startAug 2009
  3. Primary completionDec 2014
  4. Study completionAug 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
853 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00973609
Sponsor's protocol ID
AIO-KRK-0207
Other IDs
ML21768, EudraCT-Nr.: 2008-007974-39
Status last verified
Aug 2015
First submitted
19 Aug 2009
Last updated
1 Sep 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Lueong SS, Herbst A, Liffers ST, Bielefeld N, Horn PA, Tannapfel A, Reinacher-Schick A, Hinke A, Hegewisch-Becker S, Kolligs FT, Siveke JT. Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial. Clin Chem. 2020 Dec 1;66(12):1510-1520. doi: 10.1093/clinchem/hvaa223.

    PubMed 33257977

  • Hegewisch-Becker S, Nopel-Dunnebacke S, Hinke A, Graeven U, Reinacher-Schick A, Hertel J, Lerchenmuller CA, Killing B, Depenbusch R, Al-Batran SE, Lange T, Dietrich G, Tannapfel A, Arnold D. Impact of primary tumour location and RAS/BRAF mutational status in metastatic colorectal cancer treated with first-line regimens containing oxaliplatin and bevacizumab: Prognostic factors from the AIO KRK0207 first-line and maintenance therapy trial. Eur J Cancer. 2018 Sep;101:105-113. doi: 10.1016/j.ejca.2018.06.015. Epub 2018 Jul 20.

    PubMed 30036739

  • Quidde J, Hegewisch-Becker S, Graeven U, Lerchenmuller CA, Killing B, Depenbusch R, Steffens CC, Lange T, Dietrich G, Stoehlmacher J, Reinacher A, Tannapfel A, Trarbach T, Marschner N, Schmoll HJ, Hinke A, Al-Batran SE, Arnold D. Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial. Ann Oncol. 2016 Dec;27(12):2203-2210. doi: 10.1093/annonc/mdw425. Epub 2016 Oct 17.

    PubMed 27753609

  • Hegewisch-Becker S, Graeven U, Lerchenmuller CA, Killing B, Depenbusch R, Steffens CC, Al-Batran SE, Lange T, Dietrich G, Stoehlmacher J, Tannapfel A, Reinacher-Schick A, Quidde J, Trarbach T, Hinke A, Schmoll HJ, Arnold D. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1355-69. doi: 10.1016/S1470-2045(15)00042-X. Epub 2015 Sep 8.

    PubMed 26361971

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab in people with Colorectal Neoplasms, run by AIO-Studien-gGmbH at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to failure of maintenance and reinduction treatment strategy measured from randomization (time frame: From randomization until second progression after reinduction treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00973609, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2015.

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