A study to compare efficacy of cabazitaxel versus Docetaxel in recurrent head & neck cancer
- Conditions
- Patients with recurrent Head & Neck cancers
- Registration Number
- CTRI/2015/06/005848
- Lead Sponsor
- Tata Memorial Hospital
- Brief Summary
**Study methodology:**
Patients fulfilling the inclusion/exclusioncriteria would be assigned to treatment either with Cabazitaxel (Jevtana -dose: 20mg/m2 given 3 weekly) or Docetaxel (dose: 75 mg/m2given 3 weekly). Cabazitaxel or Docetaxel will be given to the patients tillprogressive disease. Patients will be seen weekly till chemotherapy iscomplete. Efficacy assessment utilizing CT scan will be performed every 6 weekswhile the patient is on treatment and every 8 weeks during the follow-up period forpatients who have not progressed on study treatment. All recruited patients would be followed up every 3months for a period of 2 years.
Tissue taken at diagnosis (if specimen available) and tissue at studyentry will be taken and stored. This tissue will also be used for exploratoryanalysis of possible factors /gene mutations related to chemosensitivity/chemoresistance. DNA / RNA samples from the tumor samples of responders and nonresponders will be analysed and correlated to the DNA/RNA sequence profile toidentify signatures. If possible, biopsy will also be taken after two cycles ofchemotherapy. MDR1expression will be quantified and correlated with response.
Qualityof Life (QOL) will be assessed using EORTC QLQ-C30 and EORTC QLQ-H&N35questionnaires. The EORTC QLQ-C30 is a 30 item questionnaire composed ofmulti-item scales that reflects the multidimensionality of the QOL construct.It incorporates five functional scales (physical, role, cognitive emotional andsocial), three symptom scales – fatigue, pain, nausea and vomiting, globalhealth scale and additional symptoms commonly reported by cancer patients aswell as the perceived financial impact of disease and treatment. Score rangesfrom 0 to 100. A higher score represents a higher level of functioning or agreater degree of symptoms. Similarly, head and neck cancer specific module(EORTC QLQ-H&N35) includes 35 items. Patients have to indicate the extentto which they have experienced the symptoms or problems during the past week.Score ranges from 1 to 4. High score for an item means worse QOL or moreproblems.
Visit0 (Baseline) Day -21 to 0
- Written informed consent
- Inclusion/exclusion criteria
- Demographics, physical examination, vital signs, ECOG-PS
- CBC, LFT, Creatinine
- CT-Scan
- QOL scales (EORTC QLQ-C30 and EORTC QLQ-H&N35)
- Assessment of adverse events and concomitant medications
- Biopsy and blood sample for biomarker analysis
Cycle1
- Day 1: Randomization, study drug administration, assessment of adverse events and concomitant medications
- Day 8 and 15: CBC, assessment of adverse events and concomitant medications
Cycle2
- Day 1: Physical examination, vital signs, ECOG-PS, CBC, creatinine, LFT, study drug administration, QOL scales (EORTC QLQ-C30 and EORTC QLQ-H&N35), assessment of adverse events and concomitant medications
- Day 8 and 15: CBC, assessment of adverse events and concomitant medications
- Day 21: CT-scan (after every 2 cycles), Biopsy (if possible)
Cycle3 to N
- Day 1: Physical examination, vital signs, ECOG-PS, CBC, creatinine, LFT, Study drug administration, QOL scales (EORTC QLQ-C30 and EORTC QLQ-STO22), assessment of adverse events and concomitant medications
- Day 8: CBC, assessment of adverse events and concomitant medications
Endof Treatment Visit
- Physical examination, vital signs, ECOG-PS, CBC, creatinine, LFT
- Biopsy (DNA/RNA extraction for sequencing)
- QOL scales (EORTC QLQ-C30 and EORTC QLQ-H&N35),
- Assessment of adverse events and concomitant medications
Afterend of treatment visit (EOT), patients will be followed-up every 3 months forup to 2 years or until death, whichever comes first. During the follow-upvisits information on survival and disease progression (if not progressedearlier) will be collected. Ongoing SAE and new or ongoing related AE will befollowed-up in follow-up period up to recovery or stabilization.
**Safety Assessment**
Adverse events will be recorded and graded as perCommon Terminology Criteria for Adverse Events (CTC AE Version 4.03) for allpatients from the signing of informed consent to the end of the study. In the event of side-effect(s),follow-up would be conducted until the symptoms are resolved. The type andseverity of the side-effect, date of onset, date of disappearance,continuation/discontinuation of the protocol therapy, and measures taken(symptomatic treatments), would be recorded on the case record forms asaccurately as possible. In addition, causal relationships between a side-effectand the trial drug(s), as well as the rationales for that assessment, wouldalso be recorded as precisely as possible. The causal relationship between anadverse event (side-effect as well as abnormal clinical laboratory finding) andthe trial drug(s) would be assessed by the clinician. Investigators arerequired to assess if there is a reasonable causal relationship with the studydrug/treatment regimen administered for each reported AE. “Reasonable causal relationship†means that,in the Investigators best clinical judgment, there are facts/evidence orarguments to suggest a causal relationship. Possible answers are ‘Yes’ or ‘No’.
**EfficacyAssessment**
Diseasecontrol/clinical benefit rate (CR/PR/SD) would be assessed as per RECIST 1.1for all randomized patients as per intent-to-treat efficacy analysis. Patients with measurable disease atbaseline will only be included in the study. When more than one measurablelesion is present at baseline all lesions up to a maximum of five lesions intotal (and a maximum of two lesions per organ) representative of all involvedorgans will be identified as target lesions and will be recorded and measuredat baseline. A sum of the diameters (longest for non-nodal lesions, short axisfor nodal lesions) for all target lesions will be calculated and reported asthe baseline sum diameters. The baseline sum diameters will be used asreference to further characterize any objective tumour regression in themeasurable dimension of the disease. Allother lesions (or sites of disease) including pathological lymph nodes will beidentified as non-target lesions and will also be recorded at baseline.
**Molecular Analysis**
Patients resistant tofirst line chemotherapy will be subjected to a punch biopsy and the tissueretrieved will be cut into smaller pieces and frozen down in liquid nitrogen.Similarly a 5ml sample of the patient’s blood will be collected and subjectedto DNA extraction as per standard manufacturer protocols for the same. The DNAsample will be re-suspended in Tris-EDTA (10:1, pH 8.0) and stored at -700C. At the end of the study, if the patient is found to be resistant to thesecond-line therapy (either taxotere or cabazitaxel), a second punch biopsywill be conducted and the tissue will be once again cut into smaller pieces andfrozen down. On completion of the study, all patient responses to cabazitaxelas a second-line therapy will be compiled and the cohort will be divided into 2groups of a) Responders and b) Non-responders, as per the criteria of “>50%â€reduction in tumor size indicating a “responder†phenotype. Three tissue samplesfrom 3 separate patients from the “responder†group will be subjected toMacromolecule extraction protocols (DNA and RNA extraction) and stored alongwith the matched DNA sample retrieved from the respective patient’s bloodsample. These samples will also be subjected to Immuno Histo-chemical analysis(IHC) to determine tumor fragments having >80% tumor cells and only samplesmeeting this criterion will be preferentially selected for further molecularanalysis. Similarly three tissue samples from 3 separate patients from the“non-responder†group will be subjected to macromolecule extraction protocolsand the DNA and RNA obtained will be stored at -700 C along with thematched blood DNA sample. Once again, these samples will be subjected to ImmunoHisto-chemical analysis (IHC) to determine tumor fragments having >80% tumorcells and only samples meeting this criterion will be preferentially selectedfor further molecular analysis. These samples will then be sent to NextGeneration Sequencing Facilities (NGS), where they will be appropriatelyprocessed for further analysis. New tumors or secondaries that develop in spiteof cabazitaxel will also be sampled for NGS studies. **Investigational Treatments**
Cabazitaxel20mg/m2 given 3 weekly until progressive disease
Docetaxel: ÂÂÂÂÂÂÂÂÂ75 mg/m2 given 3weekly until progressive disease
Pre-medication for Cabazitaxel and Docetaxel ismandatory and will follow the manufacturer’s recommendations (Appendix II andIII). All patients will be given primary prophylaxis with G-CSF.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Yet Recruiting
- Sex
- All
- Target Recruitment
- 92
- Inclusion Criteria: 1.Male or female patient, greater than or equal to 18 years of age.
- 2.Written informed consent must be obtained prior to any study related procedures.
- 3.Life expectancy of at least 3 months.
- 4.Histologically or cytologically confirmed squamous cell carcinoma of head and neck cancer excluding salivary gland.
- 5.Measurable disease on cross sectional imaging that is at least 2 cm in longest diameter (1 cm if measured by spiral CT).
- 7.Adequate bone marrow, liver, and renal function: Neutrophils ≥ 1500 /mm3; Hemoglobin ≥ 8.5 g/dL; Platelets ≥ 100 x109/L; Bilirubin ≤ ULN; SGOT (AST) ≤ 2.5 x ULN; SGPT (ALT) ≤ 2.5 x ULN; Creatinine ≤ 1.5 x ULN.
- 8.Female patients must have a negative blood pregnancy test at baseline (not applicable to patients who have had bilateral oophrectomy and/ or hysterectomy or to those patients who are > 1 year postmenopausal).
- 9.All patients of reproductive age group must agree to use of an approved form of contraception.
- 10.Should have failed at least one line of therapy (excluding taxanes) for locally advanced or metastatic head and neck cancer.
- Adjuvant chemotherapy with relapse within 6 months after end of adjuvant therapy will be considered as first line of therapy.
- Exclusion Criteria: 1.No prior taxanes.
- 2.Known allergy to taxanes.
- 3.Prior hypersensitivity to polysorbate 80.
- 4.Grade 2 or higher peripheral neuropathy (e.g. Numbness, tingling and/or pain in distal extremities.
- 5.Symptomatic or clinically active CNS disease or metastatic lesions (prior radiotherapy to brain metastases is allowed).
- 6.Major surgery within last 4 weeks and end of prior radiotherapy within last 6 weeks.
- 7.Pregnant or breast feeding women.
- 8.Uncontrolled intercurrent disease (diabetes, hypertension, thyroid disease).
- 9.Any uncontrolled coronary artery disease or cerebrovascular disease or transient ischemic attack.
- 10.Cardiac arrhythmia requiring medical therapy.
- 11.Known infection with HIV or active infection with Hepatitis B and C.
- 12.Patients unwilling to comply with the study procedures.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare the disease control with Cabazitaxel monotherapy in patients to justify its viability as a second line therapy option in patients with recurrent / metastatic head and neck cancer. At 6 weeks
- Secondary Outcome Measures
Name Time Method 1. To determine overall survival (OS), response rate and progression free survival (PFS) 2. To evaluate safety of Cabazitaxel utilizing NCI-CTC version 4.03
Trial Locations
- Locations (1)
Tata Memorial Hospital
🇮🇳Mumbai, MAHARASHTRA, India
Tata Memorial Hospital🇮🇳Mumbai, MAHARASHTRA, IndiaDr Kumar PrabhashPrincipal investigator09224182898kprabhash1@gmail.com