Advancing Cancer-care through CANScript Enabled 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

Cancer constitutes a heterogeneous group of disease whose clinical identification and prognosis presents numerous challenges. In many of the adult patients with advanced cancer, there is a higher chance of recurrence and once recurred, the chances of cure are slim.Additionally, once relapse occurs the outcomes are very poor. Though there are many options available for second line treatment. So can we develop a mechanism by which we can identify which patients will respond to a particular CT agent or combination of CT agents or more importantly not respond to the same, prior to starting therapy? There is still a substantial need for screening methods to predict therapeutic effectiveness of drug treatment regimens. Ultimately, a successful predictive method would provide maximum benefits to patients while greatly enhancing the cost effectiveness and efficiency of cancer treatment. Mitra Biotech has developed a personalized preclinical platform (“CANScript™†tumor explant technology) appropriate for testing the chemo-sensitivity and chemo-resistance of human solid cancers including Head and Neck Cancer, Breast cancer, Colorectal cancer, GI cancer, Pancreatic cancer, Peritoneal cancer and Esophagus cancer. CANScriptTM helps predict the response of the patient under investigation to a set of approved drugs for his/her type of cancer. This is done using fresh tumor tissue from the patient in a specially coated 96/384 well plate. The plates are coated with specific set of tumor matrix proteins. Further, patient derived autologousligands are added to the culture. Angiogenic factors are added to maintain tumor vasculature along with autologous immune cells. The test is carried out in multiplicates to take into account the heterogeneous nature of cancer. CANScriptâ„¢ results are measured by both kinetic as well as end-point assays. Cell Viability, Cell death, Cell proliferation, and tumor morphology are some of the functional parameters assessed. Each of these parameters is measured by more than one assay. For example, Cell Viability is measured by WST, ATP uptake and Glucose uptake assays. Cell Proliferation is measured by Ki67, and Glucose uptake. Cell death is assessed by LDH, Activated Caspase 3, and Activated Caspase 8. Tumor morphology is assessed by H&E to examine tumor cell content, size of the tumor cells, ratio of viable cells/ dead cells, ratio of tumor cells/ normal cells. Results from each of the assays are expressed in numeric form and converted using a proprietary algorithm into a single 0-100 metric called “M-scoreâ„¢â€. Based on the clinical data collected, M-Scoreâ„¢ > 25 correlates with clinical response while M-Score < 25 correlates with clinical non-response. In the present protocol, Mitra biotech and TMH intend to evaluate the applicability of the “CANScript™†personalized preclinical tumor explant platform to accurately forecast the therapeutic efficacy of candidate targeted drugs and chemotherapeutics in patients with Triple Negative Breast cancer and Head & Neck Cancer who present with tumors that are clinically appropriate for biopsy.In the present protocol, Mitra biotech and TMH intend to evaluate the applicability of the “CANScript™†personalized preclinical tumor explant platform to accurately forecast the therapeutic efficacy of candidate targeted drugs and chemotherapeutics in patients with Triple Negative Breast cancer and Head & Neck Cancer who present with tumors that are clinically appropriate for biopsy.

Primary objective:

• To determine the predictive power of CANScriptTM by comparing CANScriptTM outcome to patient’s clinical outcome at the end of 2/3 cycles of chemotherapy in H&N cancer patients and TNBC patients.

Secondary objective:

• To determine the predictive power of CANScriptTM by comparing CANScriptTM outcome to patient’s progression free survival and overall survival when followed for a period of 2 years from the study enrollment

Study End Points

Primary endpoint:

To evaluate the predictive power of CANScriptTM by comparing CANScriptTM outcomes to clinical outcomes at the end of 2/3 cycles of chemotherapy in H&N cancer and TNBC patients.

Secondary End Point:

To evaluate the predictive power of CANScriptTM by comparing CANScriptTM outcome to patient’s progression free survival and overall survival when followed for a period of 2 years from study enrollment to disease progression or death (whichever is earlier).

This is a non-randomized, observational investigator initiated trial. For the study, H&N and TNBC patients would be screened for eligibility to be included in the study. Around 347 patients would be screened. The initial screening will check the eligibility of patients using inclusion/exclusion criteria. Assuming 25% screening failure, around 260 patients enrolled for the studywould be grouped into H&N or TNBC groups as per the cancer type. Not more than 60% patients (of 260 enrolled) would belong to one of the above mentioned subtype. The subject needs to understand and sign the Informed Consent form to participate in the study. The study would be completed once 195 evaluable patient data is available.

Treatment decisions will always be determined by the attending oncologist as per the standard of care practiced at Tata Memorial Centre. H&N cancer patients will undergo 2 cycles of selected chemotherapy following which they will be evaluated for response. Based on response the Investigator may advice a 3rd cycle of chemotherapy.Following which the patients would again be evaluated for response. On completion of the primary study chemotherapy the Investigator will decide further course of local therapy as per standard of care in the form of either:

a. Surgery

b. Radiation therapy

c. Chemo-Radio Therapy (CTRT)

H&N patients enter a long term follow-up evaluation to be conducted every 90 days from last date of local therapy up to maximum 2 years from the date of study enrollment. In the long term follow up the patients would be evaluated for Response to therapy received, Progression and Survival. TNBC patients will receive 3 cycles of chemotherapy following which they will be evaluated for response. Based on the response, the Investigator will decide to continue the therapy up to 6 cycles following which the patients would be re-evaluated for response. In some cases the patient may be further continued on some type of chemotherapy if so considered by the treating physician. TNBC patients enter a long term follow-up evaluation to be conducted every 90 days from last date of chemotherapy up to maximum 2 years from the date of study enrollment. In the long term therapy the patients would be evaluated for Response to therapy received, Progression, survival. CANScriptTM assessment will be carried out and completed in one week from the time tumor samples are received from the patient.

Statistical analysis will be performed to compare the CANScript predicted outcome with clinical outcomes.