Advancing Cancer-care through CANScriptTMEnabled Personalized Treatment(ACCEPT): A non-randomized, investigator initiated, observational trial to measure predictive power of CANScriptTM for chemotherapeutics and targeted therapy in patients with newly diagnosed, locally advanced head & neck cancer and refractory / relapsed triple negative breast cancer

Cancerconstitutes a heterogeneous group of disease whose clinical identification andprognosis presents numerous challenges. The condition is much worse forpatients with refractory/recurrent/metastatic cancers, where the outcomes aremuch poorer and cure is hardly a possibility. There is a substantial need fordeveloping screening methods to predict therapeutic effectiveness of drugtreatment regimens. A successful predictive method would provide maximumbenefits to patients while greatly enhancing the cost effectiveness andefficiency of cancer treatment.

MitraBiotech Ltd. has developed CANScript™ assay. CANScript™ assay is amulti-dimensional platform which enables challenging the patient’s own tumortissue against a number of drug combinations in a human-tumor microenviromentthat mimics tumors surroundings on an invitro plate. The test analyzes various parameters like cell viability, cellproliferation, apoptosis and tumor morphology. The CANScriptTMalgorithm draws the results of various assays to arrive at a single predictivescore called the ‘M-Score’ for each drug/drug combination. Higher the M-Score,greater is the tumor response to the drug.

Inthe present protocol, Mitra Biotech and TMH intend to evaluate the applicabilityof the “CANScript™†personalized preclinical tumor explant platform toaccurately forecast the therapeutic efficacy of candidate targeted drugs andchemotherapeutics in patients with TNBCs and H&N Ca who present with tumorsthat are clinically appropriate for biopsy.

Thestudy is an Observational Clinical Trial to reconfirm in a clinical setting thespecificity and sensitivity of CANScriptâ„¢ assay. The study will involveclassification of CANScriptâ„¢ assay results into responders & non-responders.M> 25 is responder & M < 25 is non-responder.

This is a non-randomized,observational, investigator initiated trial.

 Head & Neck (H&N) andTriple Negative Breast Cancer (TNBC) patients would be screened for eligibilityto be included in the study.

 Prior to initiating chemotherapypatients would undergo a biopsy to obtain a tumor specimen and collection ofblood sample of patients enrolled in the study.

  These samples would be used for CANScriptTMassay. The assay would be performed in vitro by using chemotherapeutic agentsthat are part of standard of care at Tata Memorial Centre  (TMC). Study patients would receivechemotherapy that is part of the Standard of Care for that disease.

Treatment decisions will always bedetermined by the attending oncologist as per the standard of care practiced atTMC.

 H&N cancer patients willundergo 2 cycles of selected chemotherapy following which they will beevaluated for response. Based on response, the Investigator may advice a 3rdcycle of chemotherapy, after which the patients would again be evaluated forresponse. On completion of the primary study chemotherapy the Investigator willdecide further course of local therapy as per standard of care in the form ofeither:

a.      Surgery

b.     Radiationtherapy (RT)

c.      Chemo-RadioTherapy (CTRT)

d.     Surgeryfollowed by either RT or CTRT

H&N patients enter a long termfollow-up evaluation to be conducted every 90 days from last date of localtherapy upto maximum 2 years from the date of study enrollment. In the longterm follow up the patients would be evaluated for response to therapyreceived, progression and survival.

TNBC patients will receive 3 cyclesof chemotherapy following which they will be evaluated for response. Based onthe response, the Investigator will decide to continue the therapy up to 6cycles following which the patients would be re-evaluated for response. In somecases the patient may be further continued on some type of chemotherapy if soconsidered by the treating physician.

TNBC patients enter a long termfollow-up evaluation to be conducted every 90 days from last date ofchemotherapy up to maximum 2 years from the date of study enrollment. In thelong term therapy the patients would be evaluated for response to therapyreceived, progression and survival.

CANScriptTM assessmentwill be carried out and completed in one week from the time tumor samples arereceived from the patient. However, the Investigator would be blinded to theresults of the assay. The sponsor also would be blinded to the outcome of theresponse to therapy.

The results of the CANScriptTMassay would be compared post un-blinding with the response that the subjectachieved as the Primary Objective Evaluation and with the time to progressionand death as the long term and Secondary Objective evaluation.

Theseoutcomes would be considered to establish the Specificity and Sensitivity ofthe CANScriptTM assay in predicting outcome of chemotherapy.