Phase 2
Completed N=12
Trial of BI 6727 (Volasertib) Monotherapy and BI 6727 in Combination With Pemetrexed Compared to Pemetrexed Monotherapy in Advanced NSCLC
Source: ClinicalTrials.gov NCT00824408 ↗Enrolled (actual)
12
Serious AEs
22.9%
Results posted
Sep 2016
Primary outcomePrimary: Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First. — 1.4; 3.3; 5.3 months — p=0.0030
Summary
The trial objective will be to evaluate whether BI 6727 monotherapy or in combination with pemetrexed may be effective in the treatment of advanced or metastatic NSCLC in patients who relapsed after or failed first-line platinum based therapy.
The secondary objectives are to identify the acceptable dose of BI 6727 in combination with pemetrexed and to characterize the pharmacokinetic profiles of BI 6727 alone. Arm A, BI6727 monotherapy arm is closed to further recruitment.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) Time From the Date of Randomization to Date of Disease Progression or Death, Whichever Occurred First. |
1.4; 3.3; 5.3 | 0.0030 sig |
| SECONDARY Objective Tumor Response, Defined as Complete Response (CR), and Partial Response (PR), Evaluated According to RECIST Criteria. |
0.0; 0.0; 0.0; 0.0; 0.0; 16.7 | >0.9999 |
| SECONDARY Overall Survival (OS) |
22.9; 17.1; 17.4 | 0.8406 |
| SECONDARY Duration of Overall Response |
23.0; 19.6; 23.4 | — |
| SECONDARY Occurrence and Intensity of AEs Graded According to CTCAE. |
0; 0; 6; 2; 6; 0 | — |
| SECONDARY Occurence of DLT |
1; 1 | — |
| SECONDARY Frequency of Patients With Possible Clinically Significant Abnormalities |
1; 2; 16; 21; 14; 4 | — |
| SECONDARY Cmax of Volasertib |
554; 635; 565 | — |
| SECONDARY Total Clearance (CL) of Volasertib |
782; 882; 867 | — |
| SECONDARY Vss of Volasertib |
6730; 6750; 6230 | — |
| SECONDARY Cmax of Pemetrexed |
131000; 115000 | — |
| SECONDARY CL of Pemetrexed |
54.4; 69.1 | — |
| SECONDARY Vss of Pemetrexed |
9.40; 13.1 | — |
Eligibility Criteria
Inclusion criteria
- Pathologic or cytologic confirmed diagnosis of NSCLC
- Recurrent, advanced or metastatic NSCLC that has progressed following one prior platinum based chemotherapy regimen (not counting adjuvant or neoadjuvant chemotherapy if completed more than 12 months prior to platinum based therapy)
- Patients who are eligible for pemetrexed as second line chemotherapy
- Measurable disease by one or more techniques (CT, MRI) according to RECIST
- Patients aged 18 years or older
- Life expectancy of at least three (3) months
- Eastern Cooperative Oncology Group (ECOG) performance Score 0-2
- Written informed consent that is consistent with ICH-GCP guidelines and local legislation
Exclusion criteria
- Treatment with an investigational drug in another clinical study within the past 28 days prior to the start of therapy or concomitantly with this study
- Anti-cancer therapy for NSCLC (except radiotherapy for palliative reasons) within the past 28 days prior to Treatment Day 1 of Cycle 1 of this trial
- Any persisting toxicities which are deemed to be clinically significant from the previous therapy
- Patients who have received more than one prior chemotherapy regimen for advanced disease (not including prior adjuvant therapy). Patients may have received prior epidermal growth factor receptor tyrosine kinase inhibitors.
- Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
- Active brain metastases (stable for 26µmol/L
- Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) less than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
- Serum creatinine level >133µmol/L and/or creatinine clearance (measured or calculated) <45 ml/min
- Clinically relevant QTc prolongation
- Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
- Pregnancy or breast feeding
- Known or suspected active alcohol or drug abuse
- Patients unable to comply with the protocol
- Any known hypersensitivity to the trial drugs or their excipients
- Patients with NSCLC of confirmed Squamous histology
Data sourced from ClinicalTrials.gov (NCT00824408). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.