ModraDoc006/r in Metastatic Castration-resistant Prostate Cancer

NCT03136640 | Completed Phase 1 DMC

• 1 other identifier: M17DOC
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

This is a safety, feasibility and pharmacokinetic study to confirm that the recommended safe dose and schedule of ModraDoc006/r (oral docetaxel with ritonavir) as determined in a previous phase I study is also safe and feasible in the target population of patients with CRPC.

Conditions

Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• The maximum tolerated dose (MTD) of ModraDoc006/r treatment

  The maximum tolerated dose (MTD) of docetaxel (as ModraDoc006 10 mg tablets) that can safely be administered in combination with ritonavir to patients with metastatic castration-resistant prostate cancer in a bi-daily weekly schedule without interruption

  Safety and tolerance will be evaluated using the CTCAEv4.03 grading system, dose limiting toxicities will be evaluated during the first 4 weeks of treatment

Secondary Outcomes (5)

• The AUC of docetaxel (area under the curve)

  Pharmacokinetic sampling during week 1 and week 2, 0-48 hrs after administration (i.e. the first 2 treatment cycles)

• The cMax (peak concentration) of docetaxel

  Pharmacokinetic sampling during week 1 and week 2, 0-48 hrs after administration (i.e. the first 2 treatment cycles)

• 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 until 28 days after the last intake, using the CTCAEv4.03 grading system]

• The preliminary anti-tumor activity of the oral docetaxel formulation

  PSA and radiological evaluation every 6 weeks, up to 30 weeks

• The dose limiting toxicities (DLT) of ModraDoc006/r treatment

  First 4 weeks of treatment

Study Arms (1)

ModraDoc006/r

EXPERIMENTAL

Weekly ModraDoc006/r treatment as ModraDoc006 (oral docetaxel) 10mg tablets combined with ritonavir 100mg tablets

Drug: ModraDoc006/r

Interventions

ModraDoc006/r DRUG

Treatment with weekly ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets

Also known as: oral docetaxel formulation

ModraDoc006/r

Eligibility Criteria

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

You may qualify if:

• Histological or cytological proven castration-resistant metastatic prostate cancer with an indication for systemic treatment with intravenous docetaxel at the discretion of the physician
• Progressive disease defined as biochemical and/or radiological progression according to the Prostate Cancer Working group 3 recommendations.
• Disease evaluable for biochemical and/or radiological response (in case disease is measurable the RECIST 1.1 criteria and the guidelines for measurement of bone lesions according to the Prostate Cancer Clinical Trials Working Group 3 will be applied, as described in "Efficacy assessment").
• Chemotherapy naïve patients. Prior treatment with abiraterone or enzalutamide as first line therapy is allowed. In case of use of enzalutamide, this should be stopped 2 weeks before the first ModraDoc006/r intake. For patients that have used enzalutamide, altered pharmacokinetic sampling should be done, as described at 'Pharmacokinetics and Circulating Tumour Cell measurements"
• Castrate levels of testosterone, defined as ≤ 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)
• Age equal or above 18 years
• Adequate haematological, renal and hepatic functions
• WHO performance status of 0-2
• Life expectancy above 3 months allowing adequate follow up of toxicity evaluation and antitumor activity;
• Able and willing to swallow oral medication
• Able and willing to undergo blood sampling
• Able and willing to give written informed consent

You may not qualify if:

• Any treatment with investigational drugs, chemotherapy or immunotherapy within 28 days prior to receiving the first dose of investigational treatment. Palliative radiotherapy is allowed before and during the study as long as this is scheduled outside the DLT-period (first 28 days) and at least 4 days after intake of study medication and no intestinal toxicity is expected from the radiotherapy.
• Patients with symptomatic brain metastases. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant therapy for at least 6 weeks are allowed to enroll. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT completed at screening, demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive anti-epileptic drugs or corticosteroid treatment indicated for brain metastasis. Patients with a history of leptomeningeal metastases are not eligible.
• Unreliable contraceptive methods. Men 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)
• Unresolved (\> grade 1) toxicities of previous therapy, excluding alopecia.
• 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;
• Bowel obstructions or motility disorders that may influence the resorption of drugs as judged by the treating physician
• Concomitant use of MDR and CYP3A modulating drugs such as Ca+- entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications, other protease inhibitors, (non) nucleoside analogues, or St. John's wort.
• Use of Bicalutamide within 14 days prior to receiving the first dose of investigational treatment
• 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
• The Netherlands Cancer Institute: collaborator

Study Sites (4)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

Location

Radboud University Medical Center

Nijmegen, 6525 GA, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3508 GA, Netherlands

Location

Related Publications (1)

• Vermunt MAC, van der Heijden LT, Hendrikx JJMA, Schinkel AH, de Weger VA, van der Putten E, van Triest B, Bergman AM, Beijnen JH. Pharmacokinetics of docetaxel and ritonavir after oral administration of ModraDoc006/r in patients with prostate cancer versus patients with other advanced solid tumours. Cancer Chemother Pharmacol. 2021 Jun;87(6):855-869. doi: 10.1007/s00280-021-04259-5. Epub 2021 Mar 20.

  PMID: 33744986 DERIVED

Study Officials

• Andre Bergman, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Three patients will start at the starting dose level. If none of these patients experiences a DLT, another three patients will be added at the same dose level. The dose will be escalated or de-escalated based on safety and pharmacokinetic parameters. The recommended dose level, defined as the maximum tolerated dose (MTD) of docetaxel (as ModraDoc006 10 mg tablets) that can safely be administered in combination with ritonavir to patients with metastatic castration-resistant prostate cancer in a bi-daily weekly schedule without interruption and results in an adequate systemic exposure to docetaxel, will be expanded to at least 20 for toxicity evaluable patients.

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: May 2, 2017
• Study Start: April 26, 2017
• Primary Completion: September 5, 2019
• Study Completion: September 5, 2019
• Last Updated: October 19, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4)