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Trial record 3 of 7 for:    modradoc

ModraDoc006/r vs Docetaxel IV in Metastatic Prostate Cancer

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ClinicalTrials.gov Identifier: NCT04028388
Recruitment Status : Recruiting
First Posted : July 22, 2019
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Modra Pharmaceuticals

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Castration-resistant Prostate Cancer Drug: Docetaxel in Parenteral Dosage Form Drug: ModraDoc006/r Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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 ORR in both groups to calculate the sample size for the pivotal study.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : July 17, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : April 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Active Comparator: 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.
Drug: 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
Other Name: Taxotere

Experimental: 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.
Drug: ModraDoc006/r
Treatment with twice daily once weekly (BIDW) ModraDoc006 (oral docetaxel) 10mg tablets in combination with ritonavir 100mg tablets
Other Name: oral docetaxel formulation




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: From baseline through study completion, an average of 1 year ]
    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 :
  1. 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 ]
    The hematological and non-hematological safety profile of ModraDoc006/r will be assessed by clinical and laboratory evaluations according to CTCAE v5.0.

  2. PSA Response Rate [ Time Frame: From baseline through study completion, an average of 1 year ]
    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

  3. PFS at 6 months [ Time Frame: Landmark analysis after last patient progressed or survived for 6 months after randomization ]
    Progression free survival (PFS) at 6 months based on RECIST v1.1

  4. PSA-PFS [ Time Frame: From baseline through study completion, an average of 1 year ]
    PSA-PFS according to PCWG3 criteria

  5. Time to PSA progression [ Time Frame: From baseline through study completion, an average of 1 year ]
    Time from randomization to the time when the PSA increases by 50% above the nadir

  6. Time to first skeletal event [ Time Frame: From baseline through study completion, an average of 1 year ]
    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).

  7. Duration of response (DOR) [ Time Frame: From baseline through study completion, an average of 1 year ]
    Duration of response (DOR) based on RECIST v1.1

  8. Time to progression (TTP) [ Time Frame: From baseline through study completion, an average of 1 year ]
    Time to progression (TTP) based on RECIST v1.1, incorporating the bone metastatic variable according to PCWG3

  9. Disease control rate (DCR) [ Time Frame: From baseline through study completion, an average of 1 year ]
    Disease control rate DCR) based on RECIST v1.1


Other Outcome Measures:
  1. FACT Global (Functional Assessment of Chronic Illness Therapy) - Global Scale [ Time Frame: From baseline through study completion, an average of 1 year ]

    The FACT-G is a 27-item HRQOL questionnaire that assesses health status in terms of 4 HRQOL dimensions: physical well-being, emotional well-being, social well-being, and functional well-being. HRQoL response is defined as a 10-point or greater increase in the global FACT score at a post-baseline assessment compared with baseline.

    Improvements in individual HRQoL domains will be investigated with weekly ModraDoc006/r as compared to the standard treatment with i.v. docetaxel. Improvements that are considered significant are in subscales of FACT:

    • ≥3 for physical wellbeing (7 items; score range 0-28)
    • ≥3 for social or family wellbeing (7 items; score range 0-28)
    • ≥3 for emotional wellbeing (6 items; score range 0-24)
    • ≥3 for functional wellbeing (7 items; score range 0-28)

  2. FACT Prostate (Functional Assessment of Chronic Illness Therapy) - Prostate scale [ Time Frame: From baseline through study completion, an average of 1 year ]

    The FACT - Prostate is a 12-item HRQOL questionnaire that assesses health status related to prostate cancer symptoms.

    HRQoL response is defined as a 10-point or greater increase in the prostate FACT score at a post-baseline assessment compared with baseline.

    Improvements in individual HRQoL domains will be investigated with weekly ModraDoc006/r as compared to the standard treatment with i.v. docetaxel. Improvements that are considered significant are in subscales of FACT - P:

    ≥3 for prostate cancer subscale (12 items; score range 0-48)


  3. FACT Taxane (Functional Assessment of Chronic Illness Therapy) - Taxane treatment scale [ Time Frame: From baseline through study completion, an average of 1 year ]

    The FACT-Taxane is a 16-item HRQOL questionnaire that assesses health status related to anti-cancer treatment with a taxane.

    HRQoL response is defined as a 10-point or greater increase in the FACT score at a post-baseline assessment compared with baseline.

    Improvements in individual HRQoL domains will be investigated with weekly ModraDoc006/r as compared to the standard treatment with IV docetaxel. Improvements that are considered significant are in subscales of FACT - P:

    ≥3 for taxane treatment subscale (16 items; score range 0-64)


  4. Treatment Satisfaction Questionnaire for Medication (TSQM) [ Time Frame: From the first visit after start of treatment until study completion, an average of 1 year. ]
    The Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 is a 14-item questionnaire to assess patients' satisfaction with medication, providing scores on four scales - side effects, effectiveness, convenience and global satisfaction. TSQM scores have a range of 0 to 100, with higher scores indicating higher satisfaction.

  5. EuroQoL-5D (EQ-5D) [ Time Frame: From baseline through study completion, an average of 1 year ]

    The EQ-5D is a standardized instrument for measuring generic health status. It has two components: health state description and evaluation.

    In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". In pain/discomfort dimension, it asks how much pain or discomfort they have, and in anxiety/depression dimension, it asks how anxious or depressed they are. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) or five-level (EQ-5D-5L) scale.

    In the evaluation part, the respondents evaluate their overall health status using the visual analogue scale (EQ-VAS).




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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04028388


Contacts
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Contact: EJ DeWit, MD +31202050188 info@modrapharmaceuticals.com

Locations
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United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89119
Contact: Kaleigh Barnett, RN    702-952-3400    Kaleigh.Barnett@usoncology.com   
Principal Investigator: Nicholas J. Vogelzang, MD         
United States, Oregon
Providence Cancer Institute Recruiting
Portland, Oregon, United States, 97213
Contact: Kathleen McIntosh, BSN    503-215-3943    Kathleen.mcintosh@providence.org   
Principal Investigator: Brendan D. Curti, MD         
United States, South Carolina
Carolina Urologic Research Center Recruiting
Myrtle Beach, South Carolina, United States, 29572
Contact: Neal Shore, MD    843-455-1220    NShore@gsuro.com   
Principal Investigator: Neal Shore, MD         
Sponsors and Collaborators
Modra Pharmaceuticals
Investigators
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Study Director: EJ DeWit, MD Modra Pharmaceuticals

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Responsible Party: Modra Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04028388     History of Changes
Other Study ID Numbers: M18MDP
First Posted: July 22, 2019    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal