Advanced Solid Tumor
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety of Metformin alone and in combination with chemotherapy or immunotherapy in patients with solid tumor cancers. The main questions it aims to answer are: * what are the toxicities of metformin at multiple dose levels * what is the maximum tolerated dose of Metformin in combination with chemotherapy or immunotherapy Participants enrolled will be treated with standard of care chemotherapy and/or immunotherapy in accordance to their disease/stage. In addition, participants will take Metformin alone for 14 days in between the first cycle of chemotherapy and the second cycle of chemotherapy to determine tolerability to the Metformin. Participants will then take Metformin daily in combination with the standard of care chemotherapy and/or Immunotherapy from cycle 2 onwards.
Interventions
DRUGMetformin
Metformin will be given for 14 days alone as a run in and then added to any standard of care chemotherapy or immunotherapy for solid tumors.
Sponsors
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically confirmed advanced solid tumor and are considered a suitable candidate for chemotherapy and/or immunotherapy or both * Are a male or female participant aged ≥ 18 years * Have provided a signed, written informed consent form * Have measurable disease per RECIST v1.1 * Have adequate hematologic, renal, liver, and coagulation function as defined by the following: 1. Hemoglobin ≥ 8 g/dL if determined suitable by the investigator for the selected chemotherapy and/or immunotherapy regimen for the particular patient 2. Absolute neutrophil count (ANC) \> 1500/mm3 3. Platelets \> 75,000/mm3 if determined suitable by the investigator for the selected chemotherapy and /or immunotherapy regimen for the particular patient 4. Estimated Glomerular Filtration Rate (eGFR) \> 45 mL/min/1.73 m2 (as described by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] 2021 equation) 5. Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Participants with known Gilbert's syndrome who have total bilirubin level ≤ 3 x ULN may be enrolled if deemed suitable for a particular patient by the investigator for the selected chemotherapy and/or immunotherapy regimen. 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x ULN. For participants with hepatic metastases, AST and ALT ≤ 5 x ULN. 7. Alkaline phosphatase (ALP) \< 2.5 x ULN. For participants with hepatic and/or bone metastases ≤ 5 x ULN * Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, and suitable for chemotherapy/IO recommended by the investigator. * Participants who have experienced expected toxicity from Cycle 1 of anticancer therapy which is unlikely to recover to grade 1 or better prior to Cycle 2 (e.g., anemia, alopecia, vitiligo, endocrine dysfunction associated with IO) and may otherwise not impact the eligibility will be allowed. * Women of child-bearing potential must agree to avoid becoming pregnant and male participants should avoid impregnating a female partner or donating sperm starting at initiation of treatment up until at least 90 days after the last dose of study drug. * Have an estimated life expectancy of at least 12 weeks
Exclusion criteria
* Patients who have or are any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities (DLTs)-Metformin only stage | From the start of Metformin run in to the end of Metformin run in. Up to 14 days | Adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0). |
| Incidence of Dose Limiting Toxicities (DLTs)-Chemotherapy or Immunotherapy (IO) plus Metformin Stage | From start of Chemotherapy or IO plus Metformin until 30 days after the end of treatment | Adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0). |
| Determine the maximum tolerated dose (MTD) of metformin in combination with chemotherapy/IO | Up to 4 months after treatment initiation | The MTD will be defined as the dose level below the dose level at which two or more patients in the same cohort experience a DLT. If none or only one patient experiences a DLT at level 5, then dose level 5 will be defined as the MTD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of overall response rate (ORR) | Up to 4 months after treatment initiation | Tumor response will be determined according to RECIST v1.1. Treatment responses will be summarized by count and percentage, and their rates will be computed along with their associated two-sided 95% confidence intervals (CIs). |
| Assessment of Duration of Response (DOR) | Up to 4 months after treatment initiation | Tumor response will be determined according to RECIST v1.1. The DOR is measured from the time measurement criteria are met for complete response (CR) or a partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). Treatment responses will be summarized by count and percentage, and their rates will be computed along with their associated two-sided 95% confidence intervals (CIs). The distributions of time-to-event data, such as DOR and PFS will be graphically summarized using Kaplan-Meier (KM) curves, and their median and 95% CIs will be estimated using KM estimates. |
| Assessment of Progression free survival (PFS) | Up to 4 months after treatment initiation | Tumor response will be determined according to RECIST v1.1. Progression-free survival (PFS) is defined as the time duration from treatment start to progression time or death, whichever occurs first. Treatment responses will be summarized by count and percentage, and their rates will be computed along with their associated two-sided 95% confidence intervals (CIs). The distributions of time-to-event data, such as DOR and PFS will be graphically summarized using Kaplan-Meier (KM) curves, and their median and 95% CIs will be estimated using KM estimates. |
Countries
United States
Contacts
CONTACTWasif Saif, M.D.
PRINCIPAL_INVESTIGATORWasif Saif, M.D.
Wayne State University
Outcome results
None listed