A clinical research study to find out if the drug buparlisib in combination with paclitaxel is safe and has beneficial effects in â??patients who have recurrent or metastatic head and neck squamous cell carcinoma pre-treated with a treatment containing platinum.
- Conditions
- Health Condition 1: null- Platinum pre-treated recurrent or metastatic head and neck squamous cell carcinoma.
- Registration Number
- CTRI/2014/04/004546
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 0
1. Patient is greater than or equal to 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 fresh tumor tissue for the analysis of PI3K-related biomarkers. One
tumor block (preferred) or a minimum of 15 unstained slides to be provided. Enrollment in
the study is contingent on the central laboratory confirming receipt of an adequate amount of 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) greater than or equal to 1.5 x 10 raised to 9 per L
• Hemoglobin greater than or equal to 9 g per dl (which may be reached by transfusion)
• Platelets greater than or equal to 100 x 10 raised to 9 per L (which may be reached by transfusion)
• INR less than or equal to 1.5
• Potassium, calcium (corrected for serum albumin) and magnesium within normal
limits (WNL) for the institution
• Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) below or
equal upper limit of normal range (or less than 3 x ULN if liver metastases are present)
• Total serum bilirubin below or equal upper limit of normal range (or less than or eual to 1.5 x ULN if liver metastases are present; or total bilirubin less than or equal to 3 x ULN with direct bilirubin below or within normal range in patients with well documented Gilbertâ??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 less than or equal to 1.5 x ULN or calculated or directly measured CrCl greater than or equal to 50 percent LLN
• (Lower Limit of Normal)
• Fasting plasma glucose (FPG) less than or equal to 120 mg per dL or less than or equal to 6.7 mmol per L
• HbA1c less than or equal to 8 percent
8. ECOG Performance Status less than or equal to 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
1. Patient received treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors;
2. Patient received treatment with a taxane as part prior treatment for metastatic disease
3. Patient treated with more than 1 prior chemotherapy regimen for recurrent/metastatic
disease (i.e. chemotherapy, chemotherapy in association with a biologic/targeted agent,)
Notes:
• Patients treated with adjuvant/neoadjuvant chemotherapy and/or concomitant chemoradiotherapy regimen that may have included biologic/targeted agent are eligible.
• Cetuximab single agent used in metastatic setting is allowed.
4. Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases
may participate . The patient must have completed any prior local treatment for
CNS metastases or equal to 28 days prior to the start of study treatment (including radiotherapy and/or surgery) & must have stable low dose of corticosteroid therapy;
5. Patient who has received wide field radiotherapy or equal to 4 weeks or limited field radiation for palliation or equal to 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (except alopecia)
6. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
7. Patient has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects
8. Patient is currently receiving increasing or chronic treatment (less than 5 days) with
corticosteroids or another immunosuppressive agent, as chronic administration of
corticosteroids ( 5 days) can induce CYP3A4
• The following uses of corticosteroids are permitted: single doses; standard
premedication for paclitaxel; topical applications (e.g., rash), inhaled sprays (e.g.,
obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
9. Patient is being treated at start of study treatment with any of the following drugs:
• Drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A4
including herbal medications
• Drugs with known risk to induce Torsades de Pointes
Note: The patient must have discontinued strong inducers for at least 1 week & strong inhibitors before the treatment is initiated. Switching to a
different medication prior to starting study treatment is allowed.
10. Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for
treatment, prophylaxis or otherwise. Therapy with heparin, LMWH, or fondaparinux is allowed;
11. Patient has a known hypersensitivity and/or contra indication to paclitaxel, standard pretreatment for paclitaxel or other products containing Cremophor;
12. Patients who have other concurrent severe and/or uncontrolled medical conditions that
would, in the investigatorâ??s judgment, contraindicate patient participation in the clinical study (eg. active or uncontrolled severe infection, chronic active hepatitis,
immunocompromised, acute/chronic pancreatitis, uncontrolled high blood pressure,interstitial lung disease, etc.)
13. Patient has a known history of HIV infection (testing not mandatory) infection
14. Patient has any of the following cardiac abnormalities:
• symp
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To estimate the efficacy of <br/ ><br>buparlisib in combination with paclitaxelTimepoint: PFS according to local <br/ ><br>radiological assessment and <br/ ><br>RECIST 1.1
- Secondary Outcome Measures
Name Time Method