Clinical Trials /

ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer

NCT04028388

Description:

This is a multicenter phase IIb 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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer
  • Official Title: A Multicentre Phase IIb Trial to Evaluate the Efficacy and Tolerability of ModraDoc006/r in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC), Suitable for Treatment With a Taxane

Clinical Trial IDs

  • ORG STUDY ID: M18MDP
  • NCT ID: NCT04028388

Conditions

  • Prostate Cancer Metastatic
  • Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
Docetaxel in Parenteral Dosage FormTaxotereDocetaxel IV
ModraDoc006/roral docetaxel formulationModraDoc006/r

Purpose

This is a multicenter phase IIb 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 IIb 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 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. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Docetaxel IVActive ComparatorThis 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.
  • Docetaxel in Parenteral Dosage Form
ModraDoc006/rExperimentalThis 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.
  • ModraDoc006/r

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 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. ANC ≥ 1.5 x 109 /L

               3. Platelet count ≥ 100 x 109 /L

               4. Hepatic function defined by serum bilirubin ≤ ULN, ALAT and 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. WHO performance status 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), CYP3A, OATP1B1, OATP1B3 and 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, 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:Evaluation of objective response rate that will be observed as measured by RECIST v1.1 criteria, in patients with metastatic prostate cancer after treatment with ModraDoc006/r or docetaxel IV

Secondary Outcome Measures

Measure:Adverse event profile (Safety)
Time Frame:Evaluation of all adverse events during the complete study treatment until 28 days after the last intake, using the CTCAE v5.0 grading system
Safety Issue:
Description:The hematological and non-hematological safety profile of ModraDoc006/r will be assessed by clinical and laboratory evaluations according to CTCAE v5.0.
Measure:PSA Response Rate
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:PSA decline of >30% and >50% decline from baseline with confirmatory read ≥4 weeks later without clinical / imaging progressive disease (PD) based on the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) recommendations
Measure:PFS at 6 months
Time Frame:Landmark analysis after last patient progressed or survived for 6 months after randomization
Safety Issue:
Description:Progression free survival (PFS) at 6 months based on RECIST v1.1
Measure:PSA-PFS
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:PSA-PFS according to PCWG3 criteria
Measure:Time to PSA progression
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:Time from randomization to the time when the PSA increases by 50% above the nadir
Measure:Time to first skeletal event
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:Time to first skeletal event, defined as the time from randomisation to the occurrence of the first skeletal-related event (i.e. radiation therapy or surgery to bone, clinically apparent pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain).
Measure:Duration of response (DOR)
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:Duration of response (DOR) based on RECIST v1.1
Measure:Time to progression (TTP)
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:Time to progression (TTP) based on RECIST v1.1, incorporating the bone metastatic variable according to PCWG3
Measure:Disease control rate (DCR)
Time Frame:From baseline through study completion, an average of 1 year
Safety Issue:
Description:Disease control rate DCR) based on RECIST v1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Modra Pharmaceuticals

Last Updated

July 19, 2019