* To determine the DLT and the MTD/RP2D of docetaxel as ModraDoc006/ritonavir that can be administered safely to patients with NSCLC in a bi-daily weekly schedule, following platinum doublet first-line treatment.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* To determine the DLT and the MTD/RP2D of docetaxel as ModraDoc006/ritonavir
that can be administered safely to patients with NSCLC in a bi-daily weekly
schedule, following platinum doublet first-line treatment.
Secondary outcome
* To determine the systemic exposure of the bi-daily ModraDoc006 in combination
with ritonavir in patients with NSCLC after platinum-doublet therapy.
* To preliminary assess anti-tumor activity of ModraDoc006/ritonavir in
patients with NSCLC.
* To establish the effect of functional genetic polymorphisms in five genes
(SLCO1B3, ABCB1, ABCC2, CYP3A4 and CYP3A5) on the pharmacokinetics of oral
docetaxel and ritonavir.
Background summary
Lung cancer is one of the leading cause of cancer related deaths in the world.
Treatment consists of surgery, radiotherapy, chemotherapy, targeted therapy, or
a combination of these therapies. Inoperable and advanced stage of non-small
cell lung cancer (NSCLC) is usually treated with chemotherapy. Platinum doublet
chemotherapy is the standard first-line treatment in these patients and is
associated with survival benefit.
In patients with NSCLC harboring Endothelial Growth Factor Receptor (EGFR)
activating mutations treatment with an EGFR tyrosine kinase inhibitor (TKI)
(erlotinib, gefinitib, afatinib) has demonstrated superior activity when
compared to standard chemotherapy. Seconda line treatment options available are
docetaxel, erlotinib and, in patients with not-squamous cell histology,
pemetrexed.
Maintenance therapy with intravenous docetaxel versus delayed docetaxel (at
progression) after first-line platinum doublet therapy has been investigated by
Fidias et al. in 2009 in a clinical trial. The trial showed a 3 month
improvement in median progression free survival with maintenance docetaxel
versus delayed docetaxel (median PFS 5.7 versus 2.7 months, respectively).
However, no benefit in overall survival was observed.
The primary aim of the current study is to determine the maximum tolerable dose
of ModraDoc006/ritonavir when given as maintenance therapy in patients with
NSCLC who did not experience disease progression after first-line standard
platinum-combination chemotherapy.
Study objective
* To determine the DLT and the MTD/RP2D of docetaxel as ModraDoc006/ritonavir
that can be administered safely to patients with NSCLC in a bi-daily weekly
schedule, following platinum doublet first-line treatment.
Study design
Patients will receive ModraDoc tablet/ritonavir bi-daily weekly.
Pharmacokinetics will be performed after the first and the second week of
treatment.
The DLT period consists of the first 4 weeks of treatment. Treatment will be
continued until progression, or unacceptable toxicity despite dose modification
or patients refusal. A totoal of 9-15 patients will be enrolled in this study.
Intervention
Patients will receive ModraDoc tablet/ritonavir bi-daily weekly. Venipunction.
On dag 1 and 8, when kinetics will be done, a venflon will be used for all
bloodsamples during 24 hours.
Study burden and risks
Patients are at risk for toxicity associated with treatment with docetaxel.
Known docetaxel related toxicity consists of myelosuppression,
gastro-intestinal complaints (nausea, vomiting, diarrhea), alopecia, nail
changes, peripheral neuropathy and edema.
Ritonavir is not expected to cause if any only mild toxicity, most common of
the gastro-intestinal tract.
Patients will be admitted to hospital twice for pharmacokinetics at the
beginning of the trial. A venous indwelling catheter will be positioned for
collection of blood samples. On day 2 and 3 of week 1 and 2 blood collection
will be performed using a venapunction.
Toxicity associated with the blood sampling consists of a bruising, or in rare
case a minor infection at the place of the puncture.
Patient will be required to visit the hospital every week during the first 6
weeks for safety evaluation. Thereafter this period will be extended to every 3
weeks.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
1.Histological or cytological proof of stage IV NSCLC.
2.Patients who did not experience disease progression after four cycles of first line standard platinum doublet chemotherapy (not including a taxane).
3.Registered and start within six weeks after the last platinum-combination therapy administration.
4.Age of 18 years or older.
5.Able and willing to give written informed consent.
6.Minimal acceptable safety laboratory values.;a. Hb *6.0 mmol/L;b. ANC of * 1.5 x 109 /L ;c. Platelet count of * 100 x 109 /L;d. Hepatic function as defined by serum bilirubin * 1.5 x ULN, ALAT and ASAT * 2.5 x ULN (5 X ULN if liver metastases are present). ;e. Renal function as defined by serum creatinine * 1.5 x ULN or creatinine clearance * 50 ml/min (by Cockcroft-Gault formula).;7. WHO performance status of 0 or 1.;8. Able and willing to swallow oral medication.
Exclusion criteria
1.Prior adjuvant or neo-adjuvant chemotherapy for NSCLC.
2.Previous treatment with a taxane.
3.Patients with suspected or known brain metastases.
4.Patients with known alcoholism, drug addiction, psychotic disorders in their history and/or other reasons, for which they are not amenable for adequate follow up.
5.Women who are pregnant or breast-feeding.
6.Both men and women enrolled in this trial who do not agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms).
7.Concomitant use of MDR and CYP3A modulating drugs and agents such as Ca¬¬+-entry blockers (verapamil, dihydropyridines), cyclosporine, (non) nucleoside analogs, St. Johns worth, macrolide antibiotics as erythromycin and clarithromycin, quinidine, quinine, tamoxifen, megestrol, concomitant use of HIV medication or other protease inhibitors, grapefruit juice (see for an extended list appendix VI).;8. Chronic use of corticosteroids corresponding to a dose of >10 mg prednisone. ;9. Unresolved (> grade 1) toxicities of previous chemotherapy, excluding alopecia.;10. Bowel obstructions or motility disorders that may influence the absorption of the study drug.;11. Pre-existing neuropathy greater than NCI-CTCAE v4.03 grade 1.;12. Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001941-10-NL |
| CCMO | NL53454.031.15 |