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Trial record 2 of 7 for:    modradoc

ModraDoc006/r in Patients With Breast Cancer

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ClinicalTrials.gov Identifier: NCT03890744
Recruitment Status : Recruiting
First Posted : March 26, 2019
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Modra Pharmaceuticals

Brief Summary:
This is a multicenter phase IIa study to evaluate the efficacy and tolerability of ModraDoc006 in combination with ritonavir (denoted ModraDoc006/r) in patients with recurrent or metastatic HER-2 negative breast cancer, that are suitable for treatment with a taxane as 1st-3rd line of therapy.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Recurrent Breast Cancer Drug: ModraDoc006/r Phase 2

Detailed Description:

This is a phase IIa, multicentre, two-stage, single-arm, clinical study with the primary objective is to determine the efficacy of ModraDoc006 in combination with ritonavir (denoted ModraDoc006/r) in patients with recurrent or metastatic HER-2 negative breast cancer, as measured by RECIST v1.1 criteria of objective response rate (ORR). To this aim, a Simon two-stage minimax design will be used, in which 14 evaluable patients will be treated in the first stage (Stage A). If 0 or ≥ 2 objective responses at week 8 (with confirmation at week 12) are observed in Stage A, no further patients will be enrolled. If 1 objective response is observed, an additional 10 patients with recurrent or metastatic HER-2 negative breast cancer will be included in the second stage (Stage B).

All patients will be treated with ModraDoc006/r, given as oral tablets twice daily once weekly (BIDW).

Patients will be radiologically assessed at week 8 and 12 by CT scan (or MRI if CT is contraindicated), and may continue to receive study medication with ongoing radiological scans every 6 weeks until disease progression (according to RECIST v1.1), unacceptable toxicity, or discontinuation for any other reason.

Furthermore, the safety and tolerability of ModraDoc006/r in the target population will be assessed. Additionally, as metastatic breast cancer may occur at older age, often coinciding with other non-malignant diseases and co-medications, this protocol investigates whether ModraDoc006/r can be applied safely in these (frail) patients.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Intervention Model Description: 14 evaluable patients will be treated in the first stage (Stage A) of this Simon two-stage minimax designed trial. If 0 or ≥ 2 objective responses at week 8 (with confirmation at week 12) are observed in Stage A, no further patients will be enrolled. If 1 objective response is observed, an additional 10 patients with recurrent or metastatic HER-2 negative breast cancer will be included in the second stage (Stage B).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentre Phase IIa Study to Evaluate the Efficacy and Tolerability of ModraDoc006/r in Patients With Recurrent or Metastatic HER-2 Negative Breast Cancer, Suitable for Treatment With a Taxane
Actual Study Start Date : January 30, 2019
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: ModraDoc006/r
Weekly ModraDoc006/r treatment as ModraDoc006 (oral docetaxel) 10mg tablets combined with ritonavir 100mg tablets
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. The 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 recurrent or metastatic HER2 negative breast cancer after treatment with ModraDoc006/r


Secondary Outcome Measures :
  1. The number of CTCAE v.4.03 toxicities during treatment with ModraDoc006/r [ Time Frame: Evaluation of toxicities during the complete study treatment until 28 days after the last intake, using the CTCAEv4.03 grading system ]
    The hematological and non-hematological toxicity profile of ModraDoc006/r will be assessed by clinical and lab evaluation and evaluated according to CTCAE v.4.03

  2. The activity data on progression-free survival (PFS) of ModraDoc006/r [ Time Frame: From baseline through study completion, an average of 1 year ]
    Evaluation of progression free interval (PFS) that will be observed as measured by RECIST v1.1 criteria, in patients with recurrent or metastatic HER2 negative breast cancer during and after treatment with ModraDoc006/r


Other Outcome Measures:
  1. The number of CTCAE v.4.03 toxicities during treatment with ModraDoc006/r in a population of frail patients [ Time Frame: Evaluation of toxicities during the complete study treatment until 28 days after the last intake, using the CTCAEv4.03 grading system ]
    The hematological and non-hematological toxicity profile of ModraDoc006/r in frail patients will be assessed by clinical and lab evaluation and evaluated according to CTCAE v.4.03



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

Inclusion Criteria:

  1. Able to give written informed consent and to comply with the protocol
  2. Histologically- or cytologically confirmed diagnosis of recurrent or metastatic HER-2 negative breast cancer
  3. Female of age 18 years or above
  4. Patients who are eligible to receive a taxane as monotherapy as 1st-3rd line of therapy for recurrent or metastatic breast cancer. A maximum of two previous lines of chemotherapy is allowed (including experimental i.e. non-registered chemotherapy alone or in combination). Re-treatment with one of the same drugs after treatment interruption for reasons of patient preference and/or progression of disease counts as a new treatment
  5. WHO performance status of 0, 1 or 2 (Appendix II)
  6. Estimated life expectancy of at least 12 weeks
  7. Resolution of toxicity of prior therapy to < grade 2 (except for alopecia and transaminases in case of liver metastases) as defined by CTCAE v5.0 (Appendix III)
  8. Evidence of measurable disease present at baseline as defined by RECIST v1.1
  9. Able and willing to swallow oral medication
  10. Able and willing to undergo radiologic scans (CT scan, or MRI if CT is contraindicated)
  11. All patients of childbearing potential must have a negative high sensitive pregnancy test at screening (urine/serum) and agree to use highly effective method for contraception from time of signing Informed Consent until at least 12 weeks after the last administration of study drug
  12. Laboratory criteria:

    • Platelet count ≥ 100 x 109 /L
    • Haemoglobin ≥ 6.0 mmol/L or 9.67 g/dL
    • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109 /L
    • Total bilirubin ≤ 1.5 x ULN, except for patients with familial bilirubinaemia (Gilbert's disease)
    • Serum ASAT and ALAT ≤ 2.5 x ULN (≤ 5 x ULN with liver metastases)
    • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula or MDRD [Modification of Diet in Renal Disease])

Exclusion Criteria:

  1. Systemic chemotherapy or radiation therapy within the last 4 weeks, endocrine based therapy and CDK4/6 inhibitors within 1 week prior to first dose of ModraDoc006/r. Single dose palliative radiation for pain relieve is allowed until one week prior to start with ModraDoc006/r (these lesions are not to be included as target lesions)
  2. Any treatment with investigational drugs (or investigational device) within 21 days prior to receiving the first dose of ModraDoc006/r
  3. Previous treatment with a taxane for recurrent or metastatic breast cancer
  4. Major surgical procedures within 21 days prior to providing informed consent
  5. Active acute or chronic infection, which is not controlled by appropriate medication (at the discretion of the treating physician)
  6. Uncontrolled or significant cardiovascular disease defined as New York Heart Association Classification III or IV
  7. Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the Investigator would impair study compliance
  8. Any medical condition that in the opinion of the Investigator would contra-indicate or preclude participation within the clinical trial, or would put the patient at high risk for treatment-related complications
  9. Previous malignancies within the last three years other than breast carcinoma, except successfully treated squamous/basal cell carcinoma of the skin, superficial bladder cancer, and in situ carcinoma of the cervix
  10. Patients with symptomatic brain metastases. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anticonvulsant therapy for at least 6 weeks are allowed to enrol. Radiotherapy for brain metastasis must have been completed at least 6 weeks prior to start of study treatment. 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). Patients are not permitted to receive anti-epileptic drugs or corticosteroid treatment indicated for brain metastasis
  11. Patients with confirmed leptomeningeal metastases
  12. Women who are pregnant or breast feeding
  13. Known positivity for Human Immunodeficiency Virus HIV-1 or HIV-2 type
  14. 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)
  15. Bowel obstructions or motility disorders that may influence the resorption of drugs as judged by the Investigator
  16. Patients with unstable ascites, defined as need for palliative paracentesis or presence of a permanent peritoneal drain in the past 4 weeks prior to first dose of ModraDoc006/r. Enrolment in patients with peritonitis carcinomatosa and malignant ascites is allowed if there is no clinical and/or radiological known or suspected motility disorder within the 4 weeks prior to the first dose of ModraDoc006/r
  17. Concomitant use of MDR, MRP, OATP1B1, OATP1B3 and CYP3A 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 (see section 5.8). These need to have been stopped at least 5 times the terminal half-life (according to Summary of Product Characteristics (SPC)) or 7 days, whichever is longest, in order to prevent interaction with the drug. Tamoxifen and megestrol need to be stopped only 1 week prior to start of the first dose of ModraDoc006/r
  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): NCT03890744


Contacts
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Contact: Marianne Keessen +31202050188 info@modrapharmaceuticals.com

Locations
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Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, B-1000
Principal Investigator: Philippe Aftimos, MD, PhD         
Centre Hospitalier Universitaire de Liège Not yet recruiting
Liège, Belgium, 4000
Principal Investigator: Guy Jerusalem, MD, PhD         
Denmark
Odense University Hospital Not yet recruiting
Odense, Denmark, 5000
Principal Investigator: Annette Raskov Kodahl, MD, PhD         
Sponsors and Collaborators
Modra Pharmaceuticals
Investigators
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Study Director: Marianne Keessen Modra Pharmaceuticals

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Responsible Party: Modra Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03890744     History of Changes
Other Study ID Numbers: M18DMB
First Posted: March 26, 2019    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action