Food Effect Study of ModraDoc006 in Combination With Ritonavir

NCT03147378 | Completed Phase 1 DMC

• 1 other identifier: N15FED
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effect of food on the pharmacokinetics of ModraDoc006 in combination with ritonavir, in an open-label, cross-over design. Patients will be randomized into two treatment groups receiving ModraDoc006/r week 1 under fasting and week 2 under fed condition, or vice versa.

Conditions

Solid Tumor, Adult

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 a high fed and fasting condition

  Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)

• The cMax (peak concentration) of docetaxel

  The cMax (peak concentration) of docetaxel given as bi-daily ModraDoc006 10 mg tablets in combination with ritonavir after administration in a high fed and fasting condition

  Pharmacokinetic sampling during 2 weeks, 0-48 hours after administration (i.e. the 2 treatment cycles)

Secondary Outcomes (2)

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

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

• The effect of functional genetic polymorphisms on the pharmacokinetics of oral docetaxel and ritonavir (to understand the mechanism of the drug-drug interaction more thoroughly)

  Sampling at baseline, the analyses will be performed retrospectively

Study Arms (2)

arm A Fasting-Fed condition

EXPERIMENTAL

ModraDoc006/r will be administered in fasting condition week 1 and in fed condition week 2

Drug: ModraDoc006/r

arm B Fed-Fasting condition

EXPERIMENTAL

ModraDoc006/r will be administered in fed condition week 1 and in fasting condition week 2

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

arm A Fasting-Fed condition; arm B Fed-Fasting condition

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 for whom no standard therapy of proven benefit exists
• Patients who might benefit from treatment with docetaxel, e.g. advanced breast, gastric, esophagus, bladder, ovarian cancer and non-small cell lung cancer, head and neck cancers, prostate cancer and carcinoma of unknown primary site.
• Age 18 years
• Able and willing to give written informed consent
• Able and willing to undergo blood sampling for pharmacokinetics
• Life expectancy 3 months
• Minimal acceptable safety laboratory values 8.1. Hb ≥ 6.0 mmol/l 8.2. ANC 1.5 x 109 /L 8.3. Platelet count 100 x 109 /L 8.4. Serum bilirubin 1.5 x ULN, ALAT and ASAT 2.5 x ULN (or 5 x ULN in case of presence of liver metastases) 8.5. Serum creatinine 1.5 x ULN or creatinine clearance 50 ml/min (by Cockcroft-Gault formula).
• WHO performance status of 1
• No radio- or chemotherapy within the last 4 weeks prior to first dose of study medication (palliative radiation on limited field for pain reduction is allowed)
• Able and willing to swallow oral medication.

You may not qualify if:

• Patients with known alcoholism, drug addiction and/or psychotic disorders in the medical history that are not suitable for adequate follow up
• Women who are pregnant or breast-feeding.
• Men and women, who do not agree to use two reliable contraceptive methods hroughout the study (adequate contraceptive methods are: use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom, diaphragm with spermicide, male sterilization, true abstinence).
• 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 analogs, St. Johns wort or macrolide antibiotics like erythromycin and clarithromycin.
• Uncontrolled infectious disease or known HIV-1 or HIV-2 infection
• Unresolved (\>grade 1) toxicities of previous chemotherapy, excluding alopecia
• Bowel obstructions or motility disorders or previous surgery that may influence the absorption of drugs
• Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity
• Pre-existing neuropathy greater than CTC grade 1
• Patients with suspected or known brain metastases, unless they have been adequately treated and are asymptomatic without use of corticosteroids (for at least 1 month)
• 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
• The Netherlands Cancer Institute: collaborator

Study Sites (1)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• Vermunt MAC, de Weger VA, Janssen JM, Lopez-Yurda MI, Keessen M, Thijssen B, Rosing H, Huitema ADR, Beijnen JH, Marchetti S. Effect of Food on the Pharmacokinetics of the Oral Docetaxel Tablet Formulation ModraDoc006 Combined with Ritonavir (ModraDoc006/r) in Patients with Advanced Solid Tumours. Drugs R D. 2021 Mar;21(1):103-111. doi: 10.1007/s40268-020-00336-x. Epub 2021 Jan 19.

  PMID: 33464545 DERIVED

Study Officials

• Serena Marchetti, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: After randomization eight patients will receive ModraDoc006/r in fasting condition week 1 and in fed condition week 2, and another eight patients will receive ModraDoc006/r in fed condition week 1 and in fasting condition week 2

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 10, 2017
• Study Start: May 10, 2017
• Primary Completion: April 4, 2018
• Study Completion: April 4, 2018
• Last Updated: October 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)