ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer

NCT ID: NCT04028388

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-17
• Study Completion Date: 2021-11-29

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.

Detailed Description

This is an open label 1:1 randomized Phase 2b trial to determine the efficacy and tolerability of oral ModraDoc006/r versus i.v. docetaxel in mCRPC subjects. Cohort 1 will receive i.v. docetaxel at 75 mg/m2 every 3 weeks (Q3W). Cohort 2 will receive 30 mg ModraDoc006 in combination with 200 mg ritonavir in the morning and 20 mg ModraDoc006 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 (BIDW). All patients will also receive 5 mg oral prednisone twice daily. Treatment in both cohorts will continue until disease progression, unacceptable toxicity, or discontinuation for any other reason. The end of the trial is defined as the time point when all subjects have discontinued trial treatment and have been given follow-up for safety measurements according to the trial assessment schedule.

Conditions

Prostate Cancer Metastatic; Castration-resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel IV

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.

Group Type: ACTIVE_COMPARATOR

Docetaxel in Parenteral Dosage Form

Intervention Type: 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

ModraDoc006/r

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.

Group Type: EXPERIMENTAL

ModraDoc006/r

Intervention Type: DRUG

Treatment with twice daily once weekly (BIDW) ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets

Interventions

Docetaxel in Parenteral Dosage Form

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

Intervention Type: DRUG

ModraDoc006/r

Treatment with twice daily once weekly (BIDW) ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets

Intervention Type: DRUG

Other Intervention Names

Taxotere; oral docetaxel formulation

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Histologically or cytologically proven prostate cancer with evidence of progressive mCRPC, defined as:

1. Castrate levels of testosterone, defined as ≤ 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)

2. Evidence of progressive metastatic disease as defined by radiographic disease progression or Prostate Specific Antigen (PSA) progression

3. With an indication for systemic treatment with docetaxel according to the standard of care

3. 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

4. Resolution of toxicity of prior therapy to < grade 2 (except for alopecia), as defined by CTCAE v5.0

5. Adequate haematological, renal and hepatic functions:

1. Hemoglobin ≥ 6.0 mmol/l (>9.6 g/dL)

2. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109 /L

3. Platelet count ≥ 100 x 109 /L

4. 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.

5. Renal function defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula, or MDRD).

6. World Health Organisation Performance Status (WHO-PS) of 0-2

7. Estimated life expectancy of at least 12 weeks

8. Able and willing to swallow oral medication

9. Able and willing to undergo radiologic scans (CT scan)

10. Able and willing to give written informed consent according to local guidelines

Exclusion Criteria

1. 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.

2. Subjects who have had prior treatment with taxanes.

3. 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.

4. 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.

5. 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.

6. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)

7. Unresolved (>grade 0 as defined by CTCAE version 5.0) gastrointestinal toxicities (pre-existing mucositis, diarrhea or nausea/vomiting)

8. Grade ≥ 2 motor ≥ 2 motor or sensory neuropathy symptoms (as defined by CTCAE version 5.0)

9. Known hypersensitivity to any of the study drugs or excipients or taxanes

10. 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

11. Bowel obstruction or motility disorder that may influence the resorption of drugs as judged by the treating physician

12. Major surgical procedures within 21 days prior to providing informed consent

13. Active acute or chronic infection, which is not controlled by appropriate medication (at the discretion of the treating physician)

14. Known positivity for Human Immunodeficiency Virus HIV-1 or HIV-2 type

15. 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)

16. Clinically significant (i.e. active) cardiovascular disease defined as stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina, or congestive heart failure within ≤ 6 months prior to first trial treatment

17. Evidence of any other medical conditions (such as treatment-resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, or pulmonary embolism within 4 weeks of randomization, or psychiatric illness, drug or alcohol abuse, physical examination or laboratory findings) that may interfere with the planned treatment, affect subject compliance or place the subject at high risk of treatment-related complications

18. Legal incapacity

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Modra Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

M Keessen, MSc, MBA

Role: STUDY_DIRECTOR

Modra Pharmaceuticals

Locations

Providence Cancer Institute

Portland, Oregon, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Nemocnice Liberec

Liberec, , Czechia

Urologicke oddeleni FTN

Prague, , Czechia

Universitätsmedizin Göttingen

Göttingen, , Germany

Studienpraxis Urologie

Nürtingen, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Orszagos Onkologiai Intezet (National Institute of Oncology)

Budapest, , Hungary

Debreceni Egyetem Klinikai Központ

Debrecen, , Hungary

Petz Aladár Megyei Oktató Kórház

Győr, , Hungary

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

Szolnok, , Hungary

Przychodnia Lekarska "KOMED"

Konin, , Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, , Poland

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie

Warsaw, , Poland

Regional State Budgetary Healthcare Institution "Altai regional oncology dispensary"

Barnaul, , Russia

Limited Liability Company "EVIMED

Chelyabinsk, , Russia

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

Krasnoyarsk, , Russia

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

Moscow, , Russia

CJSC Medical Center "AVICENNA"

Novosibirsk, , Russia

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

Clinical Oncological Dispensary of Omsk Region

Omsk, , Russia

Leningrad Region Onco Dispensary

Saint Petersburg, , Russia

Limited Liability Company "Klinika Andros [Andros Clinic]"

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

Sverdlovsk Regional Clinical Hospital No. 1

Yekaterinburg, , Russia

Countries

United States; Czechia; Germany; Hungary; Poland; Russia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

M18MDP

Identifier Type: -

Identifier Source: org_study_id