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Pretreated Metastatic Colorectal CancerPhase 1REMETYNCT03305913

Regorafenib in Combination With TAS-102 in Subjects With Metastatic Colorectal Cancer Who Have Progressed After Standard Therapy

A Phase 1 study testing TAS 102 and Regorafenib in people with Pretreated Metastatic Colorectal Cancer, 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
Search all trials

Trial summary

0116-ASG REMETY is a multicenter, open-label, non-randomized, dose-escalation Phase I study evaluating the safety and anti-tumor activity of TAS-102 administered in combination with Regorafenib in patients with metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pretreated Metastatic Colorectal Cancer
What is being tested?
TAS 102 and Regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteGermany
Study dates
31 Jul 2017to 26 Apr 2019
Phase
Phase 1
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

  • Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  • Age ≥ 18 years at time of study entry
  • Histological or cytological documentation of adenocarcinoma of the colorectal region (CRC)
  • Metastatic disease not amenable to surgical resection with curative intent
  • Study treatment must constitute 3rd-line treatment for metastatic disease. Prior treatment lines must encompass at least one fluoropyrimidine-based chemotherapy, an anti-VEGF and, in case of RAS wildtype tumors, an anti-EGFR treatment.
  • Patients treated with oxaliplatin in an adjuvant setting need to have progressed during or within 6 months of completion of adjuvant therapy to be counted as prior treatment line. Note: Neoadjuvant, perioperative or adjuvant regimens with progression more than 6 months after completion are not considered as prior treatment line for metastatic disease.
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  • Measurable disease, defined as at least one unidimensional measurable lesion on a CT scan as defined by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status <2 and life expectancy of at least 3 months
  • Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days prior to study treatment initiation:
  • Absolute neutrophil count (ANC) ≥1,500/mm3
  • Platelets ≥100,000/mm3
  • Hemoglobin ≥9.0 g/dL
  • Serum creatinine ≤1.5 x upper limit of normal (ULN)
  • Glomerular filtration rate (GFR) ≥30 mL/min/1.73m2
  • AST and ALT ≤2.5 x ULN (≤5.0 × ULN for patients with liver involvement of their cancer)
  • Bilirubin ≤1.5 X ULN
  • Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN with liver involvement of their cancer)
  • Amylase and lipase ≤1.5 x ULN
  • Spot urine must not show 1+ or more protein in urine or the patient will require a repeat urine analysis. If repeated urinalysis shows 1+ protein or more, a 24-hour urine collection will be required and must show total protein excretion <1000 mg/24 hours
  • INR/PTT ≤1.5 x ULN (Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care.)
  • Women of childbearing potential and male subjects must agree to use adequate contraception for the duration of study participation and up to 6 months following completion of therapy. Females of childbearing potential who are sexually active with a non-sterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 6 months after the final dose of investigational product.
  • Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a pregnancy test performed at a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
  • In the assessment of the investigator, patient is able to comply with study requirements.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • Prior treatment with Regorafenib, or any other tyrosine kinase inhibitor for the treatment of malignancy
  • Prior treatment with TAS-102
  • Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)].
  • Known history of/or concomitant malignancy other than mCRC likely to affect life expectancy in the judgment of the investigator
  • History of Gilbert's syndrome
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days and last chemotherapy <21 days prior to first dose of treatment
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  • Radiotherapy within 4 weeks prior to first dose of treatment
  • Active cardiac disease including any of the following:
  • Congestive heart failure (New York Heart Association NYHA) ≥Class 2
  • Unstable angina (angina symptoms at rest), new-onset angina (within the last 3 months).
  • Myocardial infarction less than 6 months before start of Day 1 of treatment.
  • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
  • Uncontrolled hypertension. (Systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg despite optimal medical management)
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment
  • Known history of human immunodeficiency virus (HIV) infection
  • Chronic hepatitis B or C infection (If hepatitis status can not be obtained from medical records re-testing is required.)
  • Patients with seizure disorder requiring medication
  • Symptomatic metastatic brain or meningeal tumors unless the patient is >6 months from definitive therapy, has a negative imaging study within 4 weeks prior to treatment initiation, and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable, provided that the dose is stable for one month prior to and following screening radiographic studies).
  • History of organ allograft
  • Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ Grade 3 (CTCAE v. 4.0) within 4 weeks prior to the start of study treatment.
  • Non-healing wound, ulcer or bone fracture
  • Renal failure requiring hemo- or peritoneal dialysis
  • Dehydration according to CTCAE v. 4.03 Grade >1
  • Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine within 4 weeks prior to the start of study treatment.
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
  • Inability to swallow oral medications
  • Any malabsorption condition
  • Unresolved toxicity higher than Grade 1 CTCAE v. 4.03 attributed to any prior therapy/procedure excluding alopecia, anemia and oxaliplatin-induced neurotoxicity (which must be ≤Grade 2) or ongoing infection >Grade 2.
  • Patients unable or unwilling to discontinue (and substitute if necessary) use of prohibited drugs for at least 2 weeks prior to Day 1 of treatment initiation.
  • Female subjects who are pregnant, breast-feeding or intent to become pregnant
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Participation in another clinical study with an investigational product during the last 30 days before inclusion
  • Previous enrollment in the present study (does not include screening failure).
  • Involvement in the planning and/or conduct of the study (applies to Bayer staff and/or staff of sponsor and/or staff of the CRO and study site)
  • Patient who might be interconnected with or dependent on the sponsor, site or the investigator Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Universitätsmedizin Mainz, I.Medizinische Klinik und Poliklinik

    Mainz, 55131

Other trials in Germany

About this study

Official title: Regorafenib in Combination With TAS-102 in Subjects With Metastatic Colorectal Cancer Who Have Progressed After Standard Therapy: A Multicenter Phase I Study

0116-ASG REMETY is a multicenter, open-label, non-randomized, dose-escalation Phase I study evaluating the safety and anti-tumor activity of TAS-102 administered in combination with Regorafenib in patients with metastatic colorectal cancer.

Read the detailed description

The primary objective is to determine safety, feasibility and the recommended phase II dose (RP2D) of a combination treatment consisting of TAS-102 and Regorafenib in subjects with mCRC who have progressed after standard therapy.

Being tested
TAS 102, Regorafenib
Keywords
mCRC

What participants receive

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

  • TAS 102Drug

    Also called Lonsurf

    TAS-102 tablet

  • RegorafenibDrug

    Also called Stivarga

    Regorafenib tablet

Study groups in NCT03305913
Study groupRoleWhat they receive
Dose Level 1ExperimentalTAS-102 25 mg/m2 BID (days 1-5 and 8-12) Regorafenib 120 mg daily (3 weeks on, 1 week off)
Receives: Drug: TAS 102; Drug: Regorafenib
Dose Level 2ExperimentalTAS-102 35 mg/m2 BID (days 1-5 and 8-12), Regorafenib 120 mg daily (3 weeks on, 1 week off)
Receives: Drug: TAS 102; Drug: Regorafenib
Dose Level 3ExperimentalTAS-102 35 mg/m2 BID, (days 1-5 and 8-12) Regorafenib 160 mg daily (3 weeks on, 1 week off)
Receives: Drug: TAS 102; Drug: Regorafenib
Dose Level -1aExperimentalTAS-102 25 mg/m2 BID, (days 1-5 and 8-12) Regorafenib 80 mg daily (3 weeks on, 1 week off)
Receives: Drug: TAS 102; Drug: Regorafenib
Dose Level -1bExperimentalTAS-102 35 mg/m2 BID, (days 1-5 and 8-12) Regorafenib 80 mg daily (3 weeks on, 1 week off)
Receives: Drug: TAS 102; Drug: Regorafenib
Dose Level -2aExperimentalTAS-102 30 mg/m2 BID (or 35 mg/m2 a.m. and 25 mg/m2 p.m.), (days 1-5 and 8-12) Regorafenib 120 mg daily (3 weeks on, 1 week off)
Receives: Drug: TAS 102; Drug: Regorafenib

What is being measured

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

  1. Maximum Tolerated Dose (MTD)

    Maximum Tolerated Dose (MTD) will be determined by recording dose limiting toxicities (DLT) occurring during the first 2 treatment cycles of each patient in each tested dose level. DLT will be identified by observing frequency and severity of specific adverse events.

    Measured: 2 months

Secondary outcomes (4)

  1. Overall Response Rate (ORR) according to RECIST 1.1 criteria

    ORR is defined as the proportion of ALL Treated Subjects whose best overall response (BOR) from baseline is either a CR or PR per RECIST 1.1 criteria. BOR is determined by the best response designation recorded between the date of subject enrollment and the date of objectively documented progression. For subjects without documented progression, all available response designations will contribute to the BOR determination.

    ORR will be evaluated by reporting absolute and relative frequencies.

    Measured: approx. 12 months

  2. Progression-free survival (PFS)

    Progression free survival will be calculated from the date of subject enrollment until the date of confirmed PD or death from any cause. If no event is observed (e.g. lost to follow-up) PFS is censored at the time of last tumor assessment.

    Measured: approx. 12 months

  3. Overall survival (OS)

    Overall Survival will be calculated from the date of subject enrollment until the date of death from any cause. If no event is observed (e.g. lost to follow-up) OS is censored at the day of last subject contact.

    Measured: approx. 12 months

  4. Incidence of Treatment-Emergent Adverse Events

    Incidence of AEs, SAEs, Treatment Emergent Adverse Events according to CTC 4.03

    Measured: approx. 12 months

Timeline

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

  1. First posted10 Oct 2017
  2. Study start31 Jul 2017
  3. Primary completion31 Oct 2018
  4. Study completion26 Apr 2019

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
According to the standard 3+3 dose finding strategy, a safety assessment will be performed after the test of each dose level (patient cohorts of n=3) and the frequency of DLTs determined. Based on the results the dose for the consecutive patient cohort will either be escalated (0/3 DLTs), repeated (1/3 DLTs) or deescalated (\>1/3 DLTs).
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03305913
Sponsor's protocol ID
0116-ASG
Other IDs
2016-001968-11, 2016
Acronym
REMETY
Status last verified
Mar 2021
First submitted
16 Aug 2017
Last updated
26 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Moehler M, Michel M, Stein A, Trojan J, Marquardt J, Tintelnot J, Waidmann O, Weinmann A, Woerns MA, Schroeder H, Maenz M, Foerster F. A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer. Future Oncol. 2021 Sep;17(25):3309-3319. doi: 10.2217/fon-2021-0278. Epub 2021 May 17.

    PubMed 33993741

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAS 102 and Regorafenib in people with Pretreated Metastatic Colorectal Cancer, 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 24 inclusion and 37 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 26 Mar 2021. 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 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.

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?

Maximum Tolerated Dose (MTD) (time frame: 2 months). 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 NCT03305913, which also lists 1 linked publication.

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 26 Mar 2021.

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