Ended Phase I and Phase II (Integrated)- Other Patients with advanced, histologically confirmed, metastatic colorectal carcinoma

A phase I/II trial of D,L-MEthadone and mFOLFOX6 in treatment of advanced colorectal cancer (MEFOX)

EU CTIS ID: 2024-519509-37-00

What this study is testing

Phase I: Evaluation of the toxicity-profile of D,L-methadone and the doselimiting toxicity (DLT) in combination with mFOLFOX6 Estimation of the maximum tolerated dose (MTD) of D,L-methadone hydrochlorid in the combination with mFOLFOX6 Evaluation of the recommended dose for phase-II-trial (RPTD) of D,Lmethadone hydrochlorid Phase II: Effect of mFOLFOX6 + D,L-methadone compared to mFOLFOX6 alone on disease control rate (DCR) defined as response (CR or PR) or stabilization (SD) of the tumor disease 12 weeks after randomization in ITT-analysis. DCR will be evaluated according to RECIST1.1 in patients with histologically confirmed chemorefractory colorectal carcinoma.

Phase I and Phase II (Integrated)- Other

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Advanced, histologically confirmed, metastatic colorectal carcinoma not suitable for resection and chemorefractory. 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)
10. ALT and AST  2.5 x ULN or  5.0 x ULN in the presence of liver metastasis (established after adequate biliary drainage)
11. White blood cell count ≥ 3.5 x 106/ml, neutrophil granulocytes count ≥ 1,5 x 106/ml, platelet count ≥ 100 x 106/ml
12. Pain that has to be controllable without concomitant use of opioids
13. Signed informed consent according to ICH/GCP and national/local regulations (participation in translational research is obligate)
14. 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

You likely can't join if

1. Microsatellite unstable CRC (MSIhigh)
10. Evidence of bleeding diathesis or coagulopathy
11. 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)
12. 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
13. Pregnancy or breastfeeding women
14. Use of cannabinoids because of overlapping and /or potentiating of potential side effects

See the full eligibility criteria

Who can join

1. Advanced, histologically confirmed, metastatic colorectal carcinoma not suitable for resection and chemorefractory. 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)
10. ALT and AST  2.5 x ULN or  5.0 x ULN in the presence of liver metastasis (established after adequate biliary drainage)
11. White blood cell count ≥ 3.5 x 106/ml, neutrophil granulocytes count ≥ 1,5 x 106/ml, platelet count ≥ 100 x 106/ml
12. Pain that has to be controllable without concomitant use of opioids
13. Signed informed consent according to ICH/GCP and national/local regulations (participation in translational research is obligate)
14. 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
15. Age ≥ 18 years
16. At least one measurable target lesion according to RECIST 1.1. Preirradiated or locally treated lesions must not be used as target lesions
2. Microsatellite stable subset (MSS) of colorectal cancer
3. 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
4. There must be an oxaliplatin free period of at least 6 months prior to start of the study medication
5. No polyneuropathy of > grade 1
6. Tumor-related ECOG performance status 0-2
7. Anticipated life expectancy  12 weeks
8. Creatinine clearance  30 ml/min
9. Serum total bilirubin level ≤ 3 x ULN

What rules you out

1. Microsatellite unstable CRC (MSIhigh)
10. Evidence of bleeding diathesis or coagulopathy
11. 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)
12. 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
13. Pregnancy or breastfeeding women
14. Use of cannabinoids because of overlapping and /or potentiating of potential side effects
15. Concomitant daily use of opioids in the last 3 months including methadone prior start of study medication
16. Subjects with known allergies to the study drugs or to any of its excipients
17. 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)
18. Congenital QT-syndrome
19. Alcohol abuse
2. Chronic infectious diseases, immune deficiency syndromes
20. Bronchial asthma
21. Liver cirrhosis > Child-Pugh classification A
22. 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
3. Polyneuropathy >grade I according to CTCAE V4.03
4. Premalignant hematologic disorders, e.g. myelodysplastic syndrome
5. Disability to understand and sign written informed consent document
6. 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 3 years of
7. Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment
8. 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)
9. Severe non-healing wounds, ulcers or bone fractions

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.