Oral Docetaxel (ModraDoc/r) in Combination With Hormonal Treatment and Radiation Therapy in High-risk Prostate Cancer

NCT03066154 | Terminated Phase 1 DMC

• 1 other identifier: N15DOP
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The optimal treatment for HRPC patients has not yet been established. Recent trials suggest a benefit from early treatment with docetaxel in the castration-sensitive setting, with an improvement in failure free survival in high risk and metastatic patients and increase in overall survival in the metastatic hormone-sensitive group. In these recent randomized controlled trials, patients were treated with hormonal therapy and radiotherapy and adjuvant docetaxel, assuming that early systemic treatment for high risk or metastatic disease could delay progression in patients with aggressive primary tumor characteristics. With the fact that docetaxel is a known radiosensitizer, combined modality treatment with docetaxel during the radiotherapy could also lead to better local control and reduction of local recurrence. Several phase I and II studies have been done in HRPC patients, to evaluate the combination of high dose radiotherapy and concurrent weekly infusions with docetaxel. Oral administration of docetaxel has many advantages above intravenously administered drugs for patients. Besides the higher patient convenience, possibly longer treatment duration can be achieved due to better safety. Frequently occurring toxicities of intravenously administered docetaxel, such as neutropenia, hypersensitivity reactions and peripheral polyneuropathy have rarely been observed with the oral docetaxel formulation ModraDoc006/r. The primary aim of the N15DOP study is to determine the maximum tolerable dose (MTD) of ModraDoc006/r when given in a weekly bidaily schedule in combined modality with high dose intensity radiotherapy and hormonal therapy in castration-sensitive prostate cancer patients with high risk disease, including positive lymph nodes.

Conditions

Prostatic Neoplasms

Keywords

High risk prostate cancer; >T2cN+M0

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose (MTD) of ModraDoc/r in the combination treatment

  MTD of ModraDoc006/r (as ModraDoc006 10 mg tablets in combination with one tablet of 100 mg ritonavir) that can safely be administered in a bi-daily weekly schedule in combination with high-dose intensity modulated radiation therapy and androgen-deprivation therapy

  12 months

Secondary Outcomes (4)

• Number of participants with treatment-related adverse events as assessed by CTCAE v.4.03 with treatment with ModraDoc006/r in combination with ADT and high dose radiotherapy

  12 months

• Number of patients that will have recurrence of prostate cancer after completion of the study treatment

  10 years

• Peak Plasma Concentration (Cmax) of docetaxel in this regime.

  12 months

• Area under the plasma concentration versus time curve (AUC) of docetaxel in this regime.

  12 months

Study Arms (1)

N15DOP

EXPERIMENTAL

Chemoradiation with ModraDoc/r and radiotherapy of the prostate in dose escalation design, followed by maintenance treatment.

Drug: oral docetaxel (ModraDoc/r); Drug: androgen deprivation therapy; Radiation: high-dose intensity-modulated radiation therapy

Interventions

oral docetaxel (ModraDoc/r) DRUG

Weekly once- or twice daily ModraDoc/r

Also known as: ModraDoc006/ritonavir

N15DOP

androgen deprivation therapy DRUG

ADT according to the standard of care

Also known as: hormonal therapy

N15DOP

high-dose intensity-modulated radiation therapy RADIATION

77 Gy in 35 fractions of 2.2 Gy, 5 fractions a week

Also known as: radiotherapy

N15DOP

Eligibility Criteria

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

You may qualify if:

• Histologically proven prostate cancer.
• All eligible patients have hormone naïve non-metastatic node positive high risk prostate cancer. Node positive cancer will be defined as radiological demonstration of more than four pelvic lymph node(s) consisting of bean shaped lymph node(s) with a short axis of minimal 10 mm and/or round lymph node(s) with a minimal size of 8 mm on PSMA, MRI or CT scan.
• High risk prostate cancer will be defined as node positive with all of the following primary tumour characteristics: Tumour stage ≥cT2c and Gleason score ≥4+3, any PSA
• Age ≥ 18 years
• No signs of metastatic disease on standard diagnostic scans.
• Normal serum testosterone levels prior to treatment
• Adequate haematological, renal and hepatic functions
• Haemoglobin ≥ 6.0 mmol/l
• ANC of ≥ 1.5 x 109 /L
• Platelet count of ≥ 100 x 109 /L
• Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 2.5 x ULN
• Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula).
• WHO performance status of 0-2
• Able and willing to undergo blood sampling for PK and PD analysis;
• Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and antitumor activity;

You may not qualify if:

• Any treatment with investigational drugs, chemotherapy or immunotherapy within 30 days prior to receiving the first dose of investigational treatment; Patients may be on ADT as long as this is has not been longer than 4 weeks prior the start of the radiotherapy.
• Patients who have had prior pelvic radiation therapy
• Patients who have had prior treatment with taxanes
• TURP within 3 months before start of the study
• Patients who have had a prostatectomy.
• Any contra-indication for MRI
• Major difficulties for marker implantation
• 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)
• Unresolved (\> grade 1) toxicities of previous chemotherapy, 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 analoga, or St. John's wort.
• Pre-existing neuropathy greater than NCI-CTCAE v4.03 grade 1.
• 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.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

Netherlands Cancer Institute

Amsterdam, 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

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Ritonavir; Androgen Antagonists; Radiotherapy, Intensity-Modulated; Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Therapeutics

Study Officials

• B van Triest, 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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2016
• First Posted: February 28, 2017
• Study Start: September 1, 2016
• Primary Completion: February 1, 2022
• Study Completion: August 1, 2022
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)