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Chemo-refractory Colorectal CarcinomaPhase 1/2MEFOXNCT05212012

D,L-MEthadone and mFOLFOX6 in Treatment of Advanced Colorectal Cancer

A Phase 1/2 study testing Maximum tolerated dose, MTD: D,L-methadone hydrochloride (Methasan® 10 mg/ml) in people with Chemo-refractory Colorectal Carcinoma, run by AIO-Studien-gGmbH at 3 sites in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a phase I/II-trial with D,L-methadone and mFOLFOX6 in the treatment of patients with histologically confirmed chemo-refractory colorectal carcinoma. The aim of the phase-I trial is to evaluate the toxicity-profile and the dose-limiting toxicity of D,L-methadone combined with mFOLFOX6. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chemo-refractory Colorectal Carcinoma
What is being tested?
Maximum tolerated dose, MTD: D,L-methadone hydrochloride (Methasan® 10 mg/ml)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
3 sitesGermany
Study dates
17 Feb 2022to Dec 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Advanced, histologically confirmed, metastatic colorectal carcinoma not suitable for resection and chemorefractory or Previously employed chemotherapy regimens and agents should comprise the following: Fluoropyrimidines, oxaliplatin, irinotecan, antiangiogenic agents (bevacizumab, aflibercept or ramucirumab), anti-EFGR-mAbs (in case of all-Ras-wildtype and left-sided primary tumor) and Trifluridin/Tipiracil (TAS102)
  • Microsatellite stable subset (MSS) of colorectal cancer
  • Prior antineoplastic therapy or radiochemotherapy is allowed up to two weeks prior to start of the study medication. However, for the phase II part of the trial, failure of this strategy must be confirmed. In case of prior radiotherapy/radiochemotherapy the target lesion used for tumor evaluation must not be in the radiation field.
  • There must be an oxaliplatin free period of at least 6 months prior to start of the study medication.
  • No polyneuropathy of > grade 1
  • Tumor-related ECOG performance status 0-2
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  • Anticipated life expectancy ≥ 12 weeks
  • Creatinine clearance ≥ 30 ml/min
  • Serum total bilirubin level ≤ 3 x ULN.
  • ALT and AST ≤ 2.5 x ULN or ≤ 5.0 x ULN in the presence of liver metastasis (established after adequate biliary drainage)
  • White blood cell count ≥ 3.5 x 106/ml, neutrophil granulocytes count ≥ 1,5 x 106/ml, platelet count ≥ 100 x 106/ml
  • Pain that has to be controllable without concomitant use of opioids
  • Signed informed consent according to ICH/GCP and national/local regulations (participation in translational research is obligate)
  • None of the following concomitant medications: MAO-B-Inhibitors, strong inductors or inhibitors of CYP3A4, antiarrhythmic drugs of class I and III or other drugs that have potential for QT-prolongation
  • Age ≥ 18 years
  • At least one measurable target lesion according to RECIST 1.1. Pre-irradiated or locally treated lesions must not be used as target lesions.

Who cannot join

  • Microsatellite unstable CRC (MSIhigh)
  • Chronic infectious diseases, immune deficiency syndromes
  • Polyneuropathy >grade I according to CTCAE V4.03
  • Premalignant hematologic disorders, e.g. myelodysplastic syndrome
  • Disability to understand and sign written informed consent document
  • Past or current history of malignancies except for the indication under this study and curatively treated:
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  • Basal and squamous cell carcinoma of the skin
  • In-situ carcinoma of the cervix
  • Other malignant disease without recurrence after at least 3 years of follow-up
  • Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment
  • History of or evidence upon physical examination of CNS disease unless adequately treated (e.g. primary brain tumor, seizure not controlled with standard medical therapy or history of stroke).
  • Severe non-healing wounds, ulcers or bone fractions
  • Evidence of bleeding diathesis or coagulopathy
  • Patients not receiving therapeutic anticoagulation must have an INR ≤ 1.4 or PTT ≤ 40 sec within 28 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution)
  • Major surgical procedures or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgical procedure during the course of the study.
  • Pregnancy or breastfeeding women.
  • Use of cannabinoids because of overlapping and /or potentiating of potential side effects
  • Concomitant daily use of opioids in the last 3 months including methadone prior start of study medication
  • Subjects with known allergies to the study drugs or to any of its excipients.
  • Treatment with another investigational drug or participation in another interventional trial (within the 14 days prior randomization or 5 plasma half-lifes of the used investigational drug, whatever is longer)
  • Congenital QT-syndrome.
  • Alcohol abuse.
  • Bronchial asthma.
  • Liver cirrhosis > Child-Pugh classification A.
  • Any psychological, familial, sociological or geographical condition potentially compromising compliance with the study protocol and the follow-up schedule; those conditions should be discussed with the patient prior to registration in the trial

Trial locations and contacts

3 sites in 1 country.

Germany3 sites

  • Universitätsklinikum Hamburg Eppendorf - II. Med.

    Hamburg, 20246

  • Stauferklinikum Schwäbisch Gmünd

    Mutlangen, 73557

  • Universitätsklinikum Ulm - Innere Med. I

    Ulm, 89081

Other trials in Germany

About this study

Official title: A Phase I/II Trial of D,L-MEthadone and mFOLFOX6 in Treatment of Advanced Colorectal Cancer - The AIO-MEFOX Trial (AIO-KRK-0119)

This is a phase I/II-trial with D,L-methadone and mFOLFOX6 in the treatment of patients with histologically confirmed chemo-refractory colorectal carcinoma.

The aim of the phase-I trial is to evaluate the toxicity-profile and the dose-limiting toxicity of D,L-methadone combined with mFOLFOX6. Furthermore, to estimate the maximum tolerated dose and the recommended dose for phase-II-trial in the treatment of patients with histologically confirmed colorectal carcinoma not amenable to or progressing while having received all standard therapies.

The primary endpoint of the randomized phase-II study is to determine the disease control rate 12 weeks after randomization of patients with histologically confirmed advanced colorectal carcinoma upon treatment with D,L methadone plus mFOLFOX6 versus mFOLFOX6 alone. Overall response rate according to RECIST1.1, progression free survival (PFS), overall survival (OS), quality of life (QoL) according to the EORTC QLQc30 questionnaire, patient-reported outcomes and safety will be evaluated as secondary objectives.

Being tested
Maximum tolerated dose, MTD: D,L-methadone hydrochloride (Methasan® 10 mg/ml)
Keywords
chemo-refractory, colorectal carcinoma, D,L-methadone, mFOLFOX6
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Maximum tolerated dose, MTD: D,L-methadone hydrochloride (Methasan® 10 mg/ml)Drug

    Dose Level D,L-methadone hydrochloride (Methasan® 10 mg/ml) In dose level I a maximum of 30 mg/day (15 mg (1,5 ml) 1-0-1) In dose level II a maximum of 35 mg/ day (17.5 mg (1,75 ml) 1-0-1) In dose level III a maximum of 40 mg/day (20 mg (2,0 ml) 1-0-1)

Study groups in NCT05212012
Study groupRoleWhat they receive
D,L-methadonehydrochloride + mFOLFOX6ExperimentalDose Level D,L-methadone hydrochloride (Methasan® 10 mg/ml) In dose level I a maximum of 30 mg/day (15 mg (1,5 ml) 1-0-1) In dose level II a maximum of 35 mg/ day (17.5 mg (1,75 ml) 1-0-1) In dose level III a maximum of 40 mg/day (20 mg (2,0 ml) 1-0-1) Treatment with mFOLFOX6 every two weeks; will be administered: Oxaliplatin at a dose of 85 mg/m² iv over two hours (day 1) LV at a dose of 400 mg/m² iv over two hours (day 1) 5-FU at a dose of 2400 mg/m² iv over 46 hours (day 1-3)
Receives: Drug: Maximum tolerated dose, MTD: D,L-methadone hydrochloride (Methasan® 10 mg/ml)

What is being measured

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

  1. Evaluation of the recommended dose for phase-II-trial

    Evaluation of the toxicity-profile of D,L-methadone and the dose-limiting toxicity (DLT) in combination with mFOLFOX6

    Measured: 18 months

  2. Disease control rate 12 weeks after randomization (ITT-population)

    Evaluation of the disease control rate of D,L-methadone plus mFOLFOX6 compared to mFOLFOX6 alone in the treatment of patients with advanced colorectal cancer. The disease control rate is defined as response (CR or PR) or stabilization (SD) of the tumor disease at 12 weeks after randomization (DCR) according to RECIST1.1.

    Measured: 12 weeks after randomization

Secondary outcomes (7)

  1. Disease control rate (DCR) 12 weeks after randomization (per-protocol-population)

    The disease control rate is defined as response (CR or PR) or stabilization (SD) of the tumor disease at 12 weeks after randomization (DCR) according to RECIST1.1

    Measured: 12 weeks

  2. Overall response rate

    All tumor evaluation is performed according to RECIST 1.1

    Measured: 46 months

  3. patient diary

    Collection compliance with a diary

    Measured: 46 months

  4. Progression-free survival

    Progression-free survival (PFS) will be defined as the time from randomization to the time of progress (according to RECIST 1.1) or death, or to the date of last tumor assessment without any such event (censored observation)

    Measured: after 46 months

  5. Overall survival

    The duration of overall survival (OS) will be determined by measuring the time interval from randomization to the date of death or last observation (censored)

    Measured: 46 months

  6. Quality of life assessment

    EORTC QLQ-C30 ("European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30)" ).

    The EORTC QLQ-C30 is composed of a global health status/QoL-score, five function scales, three symptom scales and five single items (dyspnea, insomnia, appetite loss, constipation, diarrhea). Each item has four response alternatives: (1) "not at all", (2) "a little", (3) "quite a bit", and (4) "very much" - except the two items of the global health-status/quality of life scale which have response options ranging from (1) "very poor" to (7) "excellent".

    Measured: 46 months

  7. Adverse events

    Evaluation of the safety- and tolerability profile

    Measured: 46 months

Timeline

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

  1. First posted27 Jan 2022
  2. Study start17 Feb 2022
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2025 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase I: 3+3 dose escalation study (non-randomized) - max. 18 participant after Phase I start with a Amendment Phase II: Open-label, 2:1 randomized, controlled trial - 64 participant Patients in the mFOLFOX6 alone arm are allowed to cross over and receive methadone hydrochloride in combination with mFOLFOX6 upon disease progress
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05212012
Sponsor's protocol ID
AIO-KRK-0119
Other IDs
2024-519509-37-00
Acronym
MEFOX
Status last verified
Sep 2025
First submitted
2 Nov 2021
Last updated
3 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Maximum tolerated dose, MTD: D,L-methadone hydrochloride (Methasan® 10 mg/ml) in people with Chemo-refractory Colorectal Carcinoma, run by AIO-Studien-gGmbH at 3 sites 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 16 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Evaluation of the recommended dose for phase-II-trial (time frame: 18 months). The study lists 2 primary outcomes in all. 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 NCT05212012.

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 3 Oct 2025.

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