ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer

NCT04028388 | Completed Phase 2 Results FDA Drug

• 1 other identifier: M18MDP
• Study Type: interventional
• Target: 135
• Locations: 6 countries
• Sites: 28

Brief Summary

This is a multicenter phase 2b study to evaluate the efficacy and tolerability of ModraDoc006 in combination with ritonavir (denoted ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer, suitable for treatment with a taxane.

Conditions

Prostate Cancer Metastatic; Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression Free Survival (rPFS)

  Evaluation of rPFS that will be observed as measured by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria, in patients with metastatic prostate cancer after treatment with ModraDoc006/r or docetaxel IV. Radiographic disease progression was defined by the local assessment of: * Progressive disease by RECIST v1.1. for soft tissue disease * Or the appearance of 2 or more new bone lesions on bone scan (PCWG3)

  Time from the date of randomization to the date of the first radiologic progression (per PCWG3 criteria) or death from any cause, whichever occurred first, an average of 1 year.

Secondary Outcomes (9)

• Adverse Event Profile (Safety)

  Evaluation of all adverse events during the complete study treatment until 28 days after the last intake, an average of 1 year.

• Overall Response Rate (ORR)

  From baseline during the complete study treatment, including follow-up visit 28 days after the last treatment, an average of 1 year.

• Disease Control Rate (DCR)

  From baseline through study completion, an average of 1 year

• Duration of Response (DOR)

  From baseline through study completion, an average of 1 year

• Time to Progression (TTP)

  Time from the date of randomization to the date of the first radiologic progression, an average of 1 year.

Other Outcomes (4)

• Overall Health-Related Quality of Life Response

  From baseline through to end of Cycle 10 (each cycle was 21 days)

• Summary of Improvement by Individual Health- Related Quality of Life Domains

  Improvement assessed at any timepoint from baseline through to End of Cycle 10 (each cycle was 21 days)

• Overall Health-Related Utility

  Assessed from baseline to End of Cycle 10 (each cycle was 21 days)

Study Arms (2)

Docetaxel IV

ACTIVE COMPARATOR

This study arm will receive docetaxel at 75 mg/m2 given i.v. as a one-hour infusion on day 1 every 21 days plus 5 mg oral prednisone twice daily.

Drug: Docetaxel in Parenteral Dosage Form

ModraDoc006/r

EXPERIMENTAL

This cohort will receive ModraDoc006/r 30 mg oral docetaxel in combination with 200 mg ritonavir in the morning and 20 mg oral docetaxel in combination with 100 mg ritonavir in the evening (7-12 hours after the morning dose), on Day 1, 8 and 15 of a 21-day cycle, plus 5 mg oral prednisone twice daily.

Drug: ModraDoc006/r

Interventions

Docetaxel in Parenteral Dosage Form DRUG

Treatment with IV docetaxel at 75 mg/m2 given as a one-hour infusion on day 1 every 21 days plus 5 mg oral prednisone twice daily

Also known as: Taxotere

Docetaxel IV

ModraDoc006/r DRUG

Treatment with twice daily once weekly (BIDW) 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:

• Age ≥ 18 years
• Histologically or cytologically proven prostate cancer with evidence of progressive mCRPC, defined as:
• Castrate levels of testosterone, defined as ≤ 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)
• Evidence of progressive metastatic disease as defined by radiographic disease progression or Prostate Specific Antigen (PSA) progression
• With an indication for systemic treatment with docetaxel according to the standard of care
• Measurable tumour lesions, defined as pelvic and/or extra-pelvic nodal lesions ≥1.5 cm in the short axis or visceral lesions ≥1.0 cm in the longest dimensions and measurable according to RECIST v1.1, bone metastasis as evaluated with 99mTc-methylene diphosphonate (MDP) radionuclide bone scintigraphy
• Resolution of toxicity of prior therapy to \< grade 2 (except for alopecia), as defined by CTCAE v5.0
• Adequate haematological, renal and hepatic functions:
• Hemoglobin ≥ 6.0 mmol/l (\>9.6 g/dL)
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109 /L
• Platelet count ≥ 100 x 109 /L
• Hepatic function defined by serum bilirubin ≤ Upper Limit of Normal (ULN), Alanine Amino Transferase (ALAT) and Aspartate Amino Transferase (ASAT) ≤ 1.5 x ULN concomitant with alkaline phosphatase ≤ 2.5 × ULN.
• Renal function defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula, or MDRD).
• World Health Organisation Performance Status (WHO-PS) of 0-2
• Estimated life expectancy of at least 12 weeks

You may not qualify if:

• Any treatment with investigational drugs, chemotherapy or immunotherapy within 4 weeks prior to receiving the first dose of investigational treatment. Palliative radiotherapy (1x8 Gy dose) is allowed before and during the study, but not in the week prior to start of study treatment.
• Subjects who have had prior treatment with taxanes.
• Subjects with symptomatic brain metastases. Subjects asymptomatic in the absence of corticosteroids and anticonvulsant therapy for ≥6 weeks are eligible. Radiotherapy for brain metastasis must have been completed ≥6 weeks prior to start of trial. 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). Subjects are not permitted to receive anti-epileptic drugs or corticosteroid treatment indicated for brain metastasis. Subjects with a history of leptomeningeal metastases are not eligible.
• Current malignancies other than mCRPC with exception of adequately treated basal or squamous cell carcinoma of the skin, or adequately treated non-muscular invasive bladder cancer.
• Absence of highly effective method of contraception as of cycle one day one (C1D1). Men enrolled in this trial must agree to use a highly effective contraceptive method throughout the study.
• Uncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \> 100 mm Hg)
• Unresolved (\>grade 0 as defined by CTCAE version 5.0) gastrointestinal toxicities (pre-existing mucositis, diarrhea or nausea/vomiting)
• Grade ≥ 2 motor ≥ 2 motor or sensory neuropathy symptoms (as defined by CTCAE version 5.0)
• Known hypersensitivity to any of the study drugs or excipients or taxanes
• Concomitant use of P-glycoprotein (P-gp , MDR), Cytochrome P450 (CYP)3A, Organic Anion-Transporting Polypeptide (OATP)1B1, OATP1B3 and Multidrug resistance-associated protein 2 (MRP2) modulating drugs such as Ca+- entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine and grapefruit juice, concomitant use of HIV medications, other protease inhibitors, (non) nucleoside analogues, or St. John's wort
• Bowel obstruction or motility disorder that may influence the resorption of drugs as judged by the treating physician
• Major surgical procedures within 21 days prior to providing informed consent
• Active acute or chronic infection, which is not controlled by appropriate medication (at the discretion of the treating physician)
• Known positivity for Human Immunodeficiency Virus HIV-1 or HIV-2 type
• Patients with known active infection of hepatitis B/C (HBC), or E (patients who are anti-HBC positive but HBsAg negative are eligible to participate in this study)

Sponsors & Collaborators

• Modra Pharmaceuticals: lead

Study Sites (28)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89119, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Nemocnice Liberec

Liberec, Czechia

Location

Urologicke oddeleni FTN

Prague, Czechia

Location

Universitätsmedizin Göttingen

Göttingen, Germany

Location

Studienpraxis Urologie

Nürtingen, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Orszagos Onkologiai Intezet (National Institute of Oncology)

Budapest, 6000, Hungary

Location

Debreceni Egyetem Klinikai Központ

Debrecen, Hungary

Location

Petz Aladár Megyei Oktató Kórház

Győr, Hungary

Location

Jasz-Nagykun-Szolnok Megyei - Hetenyi Geza Korhaz - Rendelointezet - Onkologiai Kozpont

Szolnok, 9700, Hungary

Location

Przychodnia Lekarska "KOMED"

Konin, Poland

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, Poland

Location

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie

Warsaw, Poland

Location

Regional State Budgetary Healthcare Institution "Altai regional oncology dispensary"

Barnaul, Russia

Location

Limited Liability Company "EVIMED

Chelyabinsk, Russia

Location

Regional State Budget Institution "Krasnoyarsk Territorial Clinical Hospital n.a. A.I.Kryzhanovskogo"

Krasnoyarsk, Russia

Location

Federal State Institution "Russian Cancer Research Center named after N. N. Blokhin" RAMS

Moscow, Russia

Location

CJSC Medical Center "AVICENNA"

Novosibirsk, Russia

Location

Federal state budget institution "National medical research radiological center " of the Ministry of healthcare of the Russian Federation, branch - A. Tsyb Medical Radiological Research Center

Obninsk, Russia

Location

Clinical Oncological Dispensary of Omsk Region

Omsk, Russia

Location

Leningrad Region Onco Dispensary

Saint Petersburg, Russia

Location

Limited Liability Company "Klinika Andros [Andros Clinic]"

Saint Petersburg, Russia

Location

National medical research center of oncology n.a. N.N. Petrov

Saint Petersburg, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, Russia

Location

Sverdlovsk Regional Clinical Hospital No. 1

Yekaterinburg, Russia

Location

MeSH Terms

Interventions

Docetaxel; Injections

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: M. Keessen
• Organization: Modra Pharmaceuticals

info@modrapharmaceuticals.com

+31202050188

Study Officials

• M Keessen, MSc, MBA

  Modra Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: One-hundred RECIST 1.1 evaluable patients will be randomized 1:1 to treatment with ModraDoc006/r versus standard i.v. docetaxel. The treatment outcome will be estimated and used as the basis for the design of the future pivotal phase 3 trial. The sample size of 50 evaluable patients per cohort will provide a sufficiently precise point estimate of the primary endpoint radiographic Progression Free Survival (rPFS) in both groups to calculate the sample size for the pivotal study.

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 22, 2019
• Study Start: July 17, 2019
• Primary Completion: November 29, 2021
• Study Completion: November 29, 2021
• Last Updated: April 17, 2024
• Results First Posted: April 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); US (4); RU (12); PL (3); CZ (2); HU (4)