Oral Docetaxel in Patients With Normal or Impaired Liver Function

NCT05084456 | Withdrawn Phase 1 DMC

• 1 other identifier: N16DOL
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single centre pharmacological and safety study to define the safety and pharmacokinetics of ModraDoc006/r in a weekly dosing schedule in patients with impaired liver function who might have benefit from a weekly docetaxel regime. The safety of ModraDoc006 in combination with ritonavir for the patients with mild and moderate impaired liver function will be evaluated with a dose escalation design.

Conditions

Solid Tumor, Adult; Impaired Liver Function

Outcome Measures

Primary Outcomes (2)

• The AUC of docetaxel (area under the curve)

  The AUC of docetaxel given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir after administration in patients with normal and impaired liver function

  Pharmacokinetic plasma sampling during 48 hours in Cycle 1 and Cycle 5 (each cycle is 7 days)

• The hematological and non-hematological toxicity profile of oral docetaxel in combination with ritonavir

  The number of CTCAE v.4.03 grade 3-4 toxicities during treatment with ModraDoc006/r

  Safety and tolerance will be evaluated during the complete study treatment untill 28 days after the last intake, using the CTCAEv4.03 grading system

Study Arms (3)

Control

EXPERIMENTAL

ModraDoc006/r will be administered in a continuous weekly dose of 30-20 mg without dose escalation. This is the established recommended phase II dose for patients with normal liver function based on previous phase I trials.

Drug: ModraDoc006/r

Child-Pugh class A

EXPERIMENTAL

ModraDoc006/r administration will start treatment with a weekly BID dose of 20-10mg ModraDoc006 in combination with ritonavir. If toxicity is acceptable, after 4 weeks an intra-patient dose-escalation will be initiated, followed by the second dose escalation after another 4 weeks.

Drug: ModraDoc006/r

Child-Pugh class B

EXPERIMENTAL

ModraDoc006/r administration will start treatment with a weekly QD dose of 20mg ModraDoc006 in combination with ritonavir. If toxicity is acceptable, after 4 weeks an intra-patient dose-escalation will be initiated, followed by the second dose escalation after another 4 weeks.

Drug: ModraDoc006/r

Interventions

ModraDoc006/r DRUG

Treatment with weekly ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets in fed or fasting condition

Also known as: Oral docetaxel formulation

Child-Pugh class A; Child-Pugh class B; Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological proof of cancer
• Patients who might benefit from a weekly (oral) docetaxel regime
• One of the following options regarding liver impairment:
• Normal liver function: Child-Pugh A classification and normal (\<ULN) values of total bilirubin and ASAT/ALAT)
• Presence of liver impairment according to the following characteristics:
• Child-Pugh A and elevated (\>ULN) values of total bilirubin and/or ASAT/ALAT (as described in table 3 or Appendix VI)
• Child-Pugh B
• Age ≥ 18 years;
• Able and willing to give written informed consent;
• WHO performance status of 0, 1 or 2;
• Able and willing to undergo blood sampling for PK analysis;
• Life expectancy \> 3 months;
• Minimal acceptable laboratory values defined as:
• Hb ≥ 6.0 mmol/L
• ANC of ≥ 1.5 x 109 /L

You may not qualify if:

• Severe liver impairment classified as Child-Pugh C
• Concomitant use of anticoagulant drugs that can or do alter the PT-INR
• Other causes of elevated bilirubin than intrinsic liver impairment (as described in appendix VII)
• Concomitant use of MDR and CYP3A modulating drugs such as Ca+-entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors, (non) nucleoside analoga, St. Johns wort or macrolide antibiotics.
• Bowel obstructions or motility disorders or gastrectomy that may influence the absorption of drugs
• Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity
• Patients with symptomatic brain metastases or with leptomeningeal metastases. Patients with brain metastases are allowed if they received adequate treatment, are asymptomatic in the absence of corticosteroid therapy and anticonvulsant therapy for at least 6 weeks. Radiotherapy for brain metastases must have been completed at least 4 weeks prior to start of study treatment. Brain metastases must be stable with verification by imaging (e.g. brain MRI or CT completed at screening).
• Unresolved \> grade 1 toxicities of previous systemic therapy, except for alopecia
• Woman who are pregnant or breast feeding;
• Unreliable contraceptive methods. Both men and women enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms)
• Radio- or chemotherapy or any treatment with investigational drugs within the last 4 weeks prior to receiving the first dose of investigational treatment (palliative limited radiation for pain reduction is allowed);
• Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
• Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair study compliance;
• Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications;
• Legal incapacity

Sponsors & Collaborators

• Modra Pharmaceuticals: lead

Study Sites (1)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Serena Marchetti, MD/PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: At least 6 evaluable patients will be included in every of the three groups: a) Controls (Child-Pugh class A with normal biochemical liver tests), b) Child-Pugh class A patients with impaired biochemical liver tests, c) Child-Pugh class B patients. Therefore a minimum of 18 evaluable patients will be included.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: October 19, 2021
• Study Start: July 1, 2017
• Primary Completion: February 1, 2020
• Study Completion: April 1, 2020
• Last Updated: October 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)