Extended Use of ModraDoc006/r

Safety of Extended Use of ModraDoc006/r in Patients With Advanced Solid Tumours

This is a study for extended use of ModraDoc006/r in patients with advanced solid tumours, available after completed treatment in one of the phase I trials with ModraDoc006/r. The primary goal is to explore the safety of extended use.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: ModraDoc006/r

Detailed Description

This is an open label extended use programme, designed to make extended use treatment with weekly ModraDoc006/r available for patients who completed treatment in one of the phase I trials with ModraDoc006/r, who might have clinical benefit of continued treatment with the oral docetaxel formulation.

Patients will receive oral docetaxel (as ModraDoc006 10 mg tablets) and ritonavir (100 mg tablet) once- or bi-daily, once a week in a fasted condition. Treatment can be continued weekly as long as the patient experiences clinical benefit from the treatment as judged by the treating oncologist, unless unacceptable toxicity despite dose modifications and supportive measures occurs.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute - Antoni van Leeuwenhoek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histological or cytological proof of cancer
2. Patients who might benefit from a weekly (oral) docetaxel regime as judged by the treating oncologist.
3. Patients who received treatment with ModraDoc006/r with acceptable safety (as judged by the PI; for criteria see below in section 3 of exclusion criteria) in phase I trials with ModraDoc006/r, including (but not limited to) the N15FED (food-interaction study), N16AED (absorption-excretion study), N16DOL (normal or impaired liver function). A maximum delay of 21 days between the last dose in the previous phase I trial and the first dose in the N17DEX is allowed.
4. Age ≥ 18 years
5. WHO performance status of 0, 1 or 2;

6. Minimal acceptable laboratory values defined as:

   1. ANC of ≥ 1.5 x 109 /L
   2. Platelet count of ≥ 100 x 109 /L
   3. Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula)
   4. Hepatic function as defined by serum bilirubin ≤ 2 x ULN, ALAT and ASAT ≤ 5.0 x ULN, except for patients who have been treated in the N16DOL study.
7. Negative pregnancy test (urine/serum) for female patients with childbearing potential, assessed at the screening visit of the previous phase I trial with ModraDoc006/r.
8. Able and willing to swallow oral medication

Exclusion Criteria:

1. 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. John's wort or macrolide antibiotics.
2. Symptomatic brain metastases or 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.
3. Clinically significant safety issues during previous therapy with ModraDoc006/r as judged by the PI, which cannot be solved by dose reduction and/or treatment delay.
4. Unreliable contraceptive methods. Both men and women using ModraDoc006/r 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).
5. Anti-cancer therapy or any treatment with investigational drugs other than ModraDoc006/r between the completion of the phase I trial with ModraDoc006/r and the start of extended use of ModraDoc006/r Palliative radiation on limited field is allowed.
6. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients. Patients with a known history of hepatitis B or C.
7. Bowel obstructions or motility disorders that may influence the resorption of drugs as judged by the treating physician.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ModraDoc006/r; Weekly ModraDoc006/r treatment as ModraDoc006 (oral docetaxel) 10mg tablets combined with ritonavir 100mg tablets	Drug: ModraDoc006/r; Treatment with weekly ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets; Other Names: oral docetaxel formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 until 28 days after the last intake, using the CTCAE v.4.03 grading system

Collaborators and Investigators

• Sponsor: Modra Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2017
• Primary Completion (Actual): May 16, 2018
• Study Completion (Actual): May 16, 2019

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: N17DEX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No