Phase II multicenter randomized, double blind, placebo controlled study assessing the efficacy of buparlisib (BKM120) plus paclitaxel vs. placebo plus paclitaxel in patients with platinum pre-treated recurrent or metastatic head and neck squamous cell carcinoma

Summary

a multi-center, randomized, double-blind, placebo-controlled phase ii trial Patients will be randomized to receive either buparlisib 100 mg daily in combination with weekly paclitaxel or buparlisib-matching placebo daily in
combination with weekly paclitaxel and will be stratified according to the number of prior lines of treatment (1 vs 2) and the region of the investigator site (north america versus Rest of the World).

approximately 150 patients will be randomized in a 1:1 ratio.

Patients will be stratified according to number of prior lines of treatment (1 vs. 2) and the region of investigator's site (north america vs. Rest of the World). it is expected that 20% of the patients with Pi3K pathway activation will be enrolled in the study. HPV status will be centrally analyzed and exploratory analysis will be conducted after enrollment.

Participant Eligibility

Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Patient is >= 18 years old;
2. Written informed consent obtained before any trial related activities and according to local
guidelines.
3. Patient has histologically/cytologically-confirmed HNSCC.
4. Patient has archival or new tumor tissue for the analysis of PI3K-related biomarkers. One
tumor block (preferred) or a minimum of 12 (15 recommended) unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount
of tumor tissue.
5. Patients with recurrent or metastatic disease after failure to platinum-based chemotherapy
(defined as progression while on or after platinum-based chemotherapy given in the
recurrent/metastatic setting). Pretreatment with cetuximab (as part of chemoradiation,
first-line therapy or maintenance, or as single agent second line regimen) is allowed
6. Measurable disease as determined by per RECIST criteria v1.1. If the only site of
measurable disease is a previously irradiated lesion, documented progression of disease
and a 4 week period since radiotherapy completion is required
7. Adequate bone marrow function and organ function as shown by:

* Absolute neutrophil count (ANC) >= 1.5 x 109/L

* Hemoglobin >= 9 g/dl (which may be reached by transfusion)

* Platelets >= 100 x 109/L (which may be reached by transfusion)

* INR <= 1.5

* Potassium, calcium (corrected for serum albumin) and magnesium within normal
limits (WNL) or < grade 1 severity according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigator

* Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 1.5 x ULN (or < 3.0 x ULN if liver metastases are present)

* Total serum bilirubin below or equal upper limit of normal range (or <= 1.5 x ULN if
liver metastases are present; or total bilirubin <= 3.0 x ULN with direct bilirubin below
or within normal range in patients with well documented Gilbert[Single Quote]s Syndrome, which
is defined as presence of episodes of unconjugated hyperbilirubinemia with normal
results from CBC count (including normal reticulocyte count and blood smear),
normal liver function test results, and absence of other contributing disease processes
at the time of diagnosis (see Appendix in the final protocol)

* Serum creatinine <= 1.5 x ULN or calculated or directly measured CrCl >= 50% LLN

* (Lower Limit of Normal)

* Fasting plasma glucose (FPG) <= 120mg/dL or <= 6.7 mmol/L

* HbA1c <= 8%
8. ECOG Performance Status <= 1
9. Patient is able to swallow and retain oral medication
Note: patients able to swallow oral medication but mostly self-nourished through gastric
or jejunal feeding tube are eligible