Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Arm A (Synbiotic Arm): Participants will receive standard platinum-based chemotherapy in combination with pembrolizumab, along with an oral synbiotic regimen containing Clostridium buty
Sponsors
Mahamana Pandit Madan Mohan Malaviya Cancer Centre (MPMMCC)
Eligibility
Inclusion criteria
Inclusion criteria: Diagnosis Histologically or cytologically confirmed advanced NSCLC Stage IV or recurrent Stage IIIB or IIIC not amenable to curative surgery or radiotherapy Both non-squamous and squamous cell carcinoma subtypes are eligible Treatment Status No prior systemic therapy for advanced or metastatic NSCLC However since NGS or mutation testing for EGFR ALK might take some time and it is not ethical to deprive symptomatic patients from one to two cycles of chemotherapy this will be allowed to ensure pragmatic inclusion and capturing more real world like situations Also patients who received adjuvant or neoadjuvant chemotherapy or immunotherapy for earlier stage disease are eligible if relapse occurred greater than or equal to 6 months after completion of that therapy Tumor Molecular Profile No known activating EGFR mutation ALK or ROS1 rearrangement that would make them candidates for targeted TKIs Patients with such oncogenic drivers typically receive targeted therapy rather than chemo immunotherapy first line If such alteration is discovered after enrolment patient can be discontinued from protocol treatment physician discretion will be taken as final Also for targetable mutations found in NGS treatment might not be available or feasible based on available resources or drug availability in the country such patients can be enrolled as per treating physician discretion Planned First Line Therapy Candidate for platinum based doublet chemotherapy combined with pembrolizumab as per standard of care For non squamous NSCLC pemetrexed plus cisplatin or carboplatin plus pembrolizumab For squamous NSCLC paclitaxel or nab paclitaxel plus carboplatin plus pembrolizumab The treating investigator should deem the patient suitable for this regimen Measurable Disease At least one measurable lesion by RECIST 1.1 criteria tumor greater than or equal to 10 mm on CT Target lesions must not lie in a previously irradiated field unless progression documented in that lesion Age and Demographics Adult patients age greater than or equal to 18 years No upper age limit patients greater than or equal to 70 years can be included and geriatric assessment though not mandatory will be encouraged if feasible Both men and women and all races or ethnicities are eligible Performance Status Eastern Cooperative Oncology Group ECOG performance status 0 to 1 fully active or restricted in vigorous activity but ambulatory Patients with ECOG 2 may be considered on a case by case basis if the performance decrement is due to symptoms from lung cancer and expected to improve with therapy stratification will ensure nearly similar allocation of such patients to both the treatment arms Organ Function Adequate hematologic and end organ function including ANC greater than or equal to 1.0 multiplied by 10 to the power 9 per liter platelets greater than or equal to 75 multiplied by 10 to the power 9 per liter hemoglobin greater than or equal to 8 g per dL AST or ALT less than or equal to 2.5 times upper limit of normal or less than or equal to 5 times if liver metastases present total bilirubin less than or equal to 2.5 times upper limit of normal or less than or equal to 3 times for Gilbert syndrome creatinine clearance greater than or equal to 45 mL per minute Cockcroft Gault or equivalent Brain Metastases Allowed if treated and or stable or asymptomatic Patients with asymptom
Exclusion criteria
Exclusion criteria: Prior Immunotherapy Any prior therapy with PD 1 or PD L1 inhibitors or CTLA 4 inhibitors in the advanced setting Prior adjuvant immunotherapy is exclusionary if completed less than 6 months before relapse Active Autoimmune Disease Patients with active known autoimmune diseases that required systemic treatment in past 2 years such as lupus rheumatoid arthritis or multiple sclerosis are excluded due to risk of immune checkpoint inhibitor toxicity Exception Patients with vitiligo type 1 diabetes hypothyroidism on hormone replacement or mild psoriasis not requiring systemic treatment may be included Immunosuppressive Therapy Chronic use of systemic corticosteroids greater than 10 mg prednisone daily or equivalent or other immunosuppressants within 14 days prior to enrollment Inhaled or topical steroids and adrenal replacement doses are allowed Short term steroid pre medication for chemotherapy is permitted Uncontrolled CNS Metastases Symptomatic brain metastases or leptomeningeal disease Patients requiring corticosteroids for CNS edema greater than 10 mg prednisone daily are excluded Patients with treated stable brain lesions as noted in inclusion are allowed Active Infection Any uncontrolled active infection requiring intravenous antibiotics Patients with ongoing Clostridioides difficile colitis or other serious gastrointestinal infection are excluded as are those with active chronic infections like tuberculosis HIV positive patients are eligible if on stable antiretroviral therapy and with CD4 greater than 200 and undetectable viral load Hepatitis B or C patients are eligible if controlled HBV DNA less than 100 IU per mL or on antivirals HCV treated or with low viral load as per treating physician discretion Recent Antibiotic Use Strong exclusion microbiome specific Antibiotic use for more than 3 days within 14 days prior to enrollment If a candidate requires antibiotics enrollment should be deferred until greater than or equal to 2 weeks after completion Patients who received antibiotics 15 to 30 days before may be enrolled but will be stratified or randomized in a balanced manner Probiotic Use Regular use of non study probiotics or fermented supplement products that contain live bacteria is not allowed from 14 days prior and during trial with the exception of yogurt or kefir as consumed in routine diet Patients must agree to discontinue any personal probiotic supplements before starting study treatment Significant GI Disorder Any condition that could interfere with oral probiotic administration or absorption such as active inflammatory bowel disease including Crohn disease or ulcerative colitis or prior major gastrointestinal surgery resulting in malabsorption Mild irritable bowel syndrome or remote history of inflammatory bowel disease in remission may be permitted with careful monitoring Concurrent Malignancies Patients with another active malignancy requiring systemic therapy are excluded except certain indolent cancers such as low risk prostate cancer on surveillance or non melanoma skin cancers Any prior cancer must be in remission and not expected to confound survival for example no exclusion for cured early cancers more than 1 year ago Cardiopulmonary Contraindications Uncontrolled cardiopulmonary comorbidities such as symptomatic heart failure unstable angina or recent myocardial infarction withi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective (Phase III): To determine whether the addition of the synbiotic regimen (CBM588 + B. longum/bifidum + L. rhamnosus GG) to first-line platinum-based chemotherapy and pembrolizumab significantly improves progression-free survival (PFS) at 6 months in patients with advanced NSCLC, compared to chemo-immunotherapy plus placebo. Hypothesis: The synbiotic will increase PFS in advanced NSCLC. Mechanistically, we hypothesize the probiotic combination will favorably alter gut microbiota (e.g. enrich Bifidobacterium, produce butyrate) leading to enhanced systemic anti-tumor immunity and thereby delaying cancer progressionTimepoint: 6 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival OS Compare survival between synbiotic and placebo Hypothesis Synbiotic improves survival with hazard ratio zero point seven to zero point eight zero Objective Response Rate ORR Compare complete and partial response Hypothesis Synbiotic increases response rate Duration of Response DoR Compare response duration Hypothesis Synbiotic gives longer lasting responses Disease Control Rate DCR Compare complete partial and stable disease for twelve weeks Hypothesis Synbiotic improves disease control Safety and Tolerability Assess adverse events Hypothesis No increase in severe toxicity possible reduction in gastrointestinal effects Patient Reported Outcomes PROs Compare quality of life and symptoms Hypothesis Synbiotic improves quality of lifeTimepoint: 6 year | — |
Countries
India
Contacts
Public ContactDr Akhil Kapoor
Mahamana Pandit Madanmohan Malviya Cancer Centre (MPMMCC)
Outcome results
None listed