Overview

ModraDoc006/r in Patients With Breast Cancer

Status:
Completed
Trial end date:
2020-11-09
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Modra Pharmaceuticals
Treatments:
Docetaxel
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