None listed
Conditions
Brief summary
This study will investigate the safety of Complete Freund’s Adjuvant (CFA) in Patients with Refractory and Relapsed Solid Tumours. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have a histologically or cytologically confirmed locally advanced or metastatic solid tumor (melanoma, head & neck, sarcoma, renal and other cancers) for which no curable therapy exists. Study details This study involves the use of an investigational drug called CFA. "Investigational" means that the drug has not yet been approved by the Therapeutic Goods Administration (TGA) for treatment of cancer. CFA consists of three ingredients: mineral oil, surfactant, and heat-killed mycobacterium. Injection of CFA into tumour creates a localised depot of killed bacteria, which are slowly released over weeks. This causes an influx of immune cells to the site on injection, and initiates a powerful immune response. The other drug (pembrolizumab) is an approved novel agent for the treatment of metastatic melanoma. Participants in the study will receive CFA in combination with pembrolizumab. CFA will be administered in 42 day cycles starting at a dose of 0.5 ml for the first cohort of three patients. These patients will be monitored closely and provided there are no safety concerns additional patients will be enrolled and treated with 1.0 ml of CFA and subsequently a third cohort will be enrolled with a starting dose of 2.0 ml of CFA. Once a participant experiences an adverse event as a result of the CFA dose, this dose level will be expanded with three additional patients enrolled. If two of the six participants experience a reaction the dose will be decreased to the previous level and three additional patients will be added. If one of the six patients experience a reaction that dose will be declared the maximum tolerated dose for CFA. Pembrolizumab will be administered following approved guidelines (2mg/kg) on day 2 of the first cycle and then every three weeks. Safety of CFA will be assessed at Day 1 of each 42 day cycle. Participants will be followed for up to 30 days after removal from treatment to determine therapeutic benefit and anti-tumour effect of CFA. Patients removed from treatment for unacceptable adverse events will be followed up until resolution or stabilization of the adverse event.
Interventions
In this study, escalating doses of single agent Complete Freund's Adjuvant (CFA) will be administered for the treatment of melanoma, head & neck cancer, sarcoma and renal cancer. Patients will be treated with a combination of intratumoural CFA and intravenous pembrolizumab to characterize the safety and anti-tumour activity of this combination.
CFA will be administered at the start of a 42 day cycle. This cycle will be repeated every 42 days at discretion of the investigator.
One cohort (3 pa
In this study, escalating doses of single agent Complete Freund's Adjuvant (CFA) will be administered for the treatment of melanoma, head & neck cancer, sarcoma and renal cancer. Patients will be treated with a combination of intratumoural CFA and intravenous pembrolizumab to characterize the safety and anti-tumour activity of this combination. CFA will be administered at the start of a 42 day cycle. This cycle will be repeated every 42 days at discretion of the investigator. One cohort (3 patients) will start at a dose level of 0.5ml of CFA, one will start at 1ml of CFA and the third will start at 2ml of CFA. At any dose level if no dose limiting toxicity (DLT) are observed, the dose will be escalated. Patients must complete 1 cycle of treatment with the minimum safety evaluation and drug exposure, or have had a DLT within the first cycle of treatment to be considered evaluable for dose escalation decisions. CFA dose can be escalated at discretion of the investigator if the patient is deriving benefit and has not experienced DLT or a serious adverse event. Intermediate or additional dose levels of CFA may also be considered depending upon the safety and tolerability of this agent. If a DLT is observed in 1 out of 3 patients at a given dose level, up to an additional 3 patients will be enrolled and treated at that dose level. If patients at that dose level have DLTs, the dose will be decreased to the previous dose level and 3 additional patients will be enrolled at that dose level. When up to 3 additional patients are added to a given dose level, if 1 of the 6 patients has a DLT, that dose will be declared as maximum tolerated dose or recommended phase II dose. If 2 of the first 3 or 2 of the total 6 patients experience DLTs at the initial dose level of 0.5 ml CFA, further enrollment will be halted and the study terminated or amended to evaluate lower doses. Dose escalation will continue until identification of the maximum tolerated dose/recommended phase II dose or a suitable lower dose for expansion. Pembrolizumab will be administered every three weeks. Dose will be 2mg/kg.
Sponsors
Canberra Hospital Medical Oncology Department
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically/cytologically confirmed locally advanced or metastatic solid tumors (melanoma, head & neck, sarcoma, renal and other cancers) for which no curable therapy exists. Melanoma patients will be allowed to enroll in the dose escalation phase of single agent study following progression or intolerance of ipilimumab/pembrolizumab (or both). Patients who are not suitable or decline treatment with ipilimumab/pembrolizumab (or both) will also be allowed to participate during dose escalation. Previous treatment with a PD1 inhibitor agent is not allowed in dose expansion phase. However, previous treatment with ipilimumab is allowed in dose expansion phase. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Adequate marrow function as defined below: a- absolute neutrophil count greater than or equal to 1.0 x 10^9/L b- platelets greater than or equal to 100,000 x 10^9/L c- INR less than 1.5 x ULN Evidence of at least one measurable and easily accessible cutaneous or subcutaneous lesion that could be injected with CFA but preferably three lesions (other two for a biopsy and tumour assessment each). In patients who have a single measurable lesion, it can be used for intratumoral injection, biopsy and response measurement. Adequate liver function as evidenced by bilirubin <1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3 times the ULN or <5.0 x ULN if liver metastases are present. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy, or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Recovery from all AE of prior cancer therapies including surgery and radiotherapy, to baseline or CTCAE Grade greater than or equal to 1, except for alopecia. No prior therapy with CFA or similar agents. Melanoma, head & neck cancer, sarcoma and renal cancer patients will be allowed to enrol in the dose escalation phase of the study. However, enrolment into dose expansion phase Ib will be restricted to melanoma patients with no prior exposure to anti-PD1 agent. Patients with treated brain metastases, provided that they are clinically stable for a period of 30 days prior to study entry. These criteria will also be in effect for the dose escalation and expansion stages of the study
Exclusion criteria
Preexisting > grade 2 peripheral neuropathy Treatment with any of the following anti-cancer therapies prior to the first dose of CFA within the stated timeframes: intravenous chemotherapy within a period of 4 weeks (6 weeks for nitrosourea, mitomycin-C), biological therapy (e.g. antibodies) within a period of time that is ~ 5 t1/2 or less than 4 weeks, whichever is shorter, prior to starting study drug, any other investigational agents within a period of time that is < 5 tl/2 or 4 weeks (whichever is shortest) prior to starting study drug, wide field radiotherapy <4 weeks or limited field radiation for palliation <2 weeks prior to starting study drug. History of cardiac disease (Congestive heart failure NYHA grade > 2, LVEF < 40% as determined by MUGA scan or ECHO, history of clinically significant ventricular arrhythmias, uncontrolled hypertension, unstable angina pectoris or acute myocardial infarction <6 months prior to starting study drug, QTcF > 450 msec), or history of Torsades de pointes. Pregnant or nursing (lactating) women. These criteria will also be in effect for the dose escalation and expansion stages of the study
Outcome results
None listed