Phase I Study of Complete Freund’s Adjuvant (CFA) in Patients with Refractory and Relapsed Solid Tumours
- Conditions
- Solid TumoursCancer - Head and neckCancer - Malignant melanomaCancer - Sarcoma (also see 'Bone') - soft tissue
- Registration Number
- ACTRN12616001637437
- Lead Sponsor
- Canberra Hospital Medical Oncology Department
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 26
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the safety and tolerability of CFA in adult subjects with locally advanced or metastatic solid tumors. <br>Dose will be maintained, reduced or discontinued based on the severity of adverse event and length of time to resolution. <br>Blood bilirubin grade 2 (>1.5-3.0 x ULN)<br>AST/ALT elevation grade 3 (>5.0 - 20.0 x ULN) without bilirubin elevation >2.0 x ULN <br>AST/ALT elevation grade 2 (>3.0 - 5.0 x ULN) AND total bilirubin >2.0 x ULN <br>ANC <1.0 x 10^9/L without fever and/or platelets <100,000 x 10^9 <br>QTc interval >481 msec<br>Grade 2 or greater tumour site skin ulceration caused by CFA treatment<br>Other clinically significant non-hematological AEs related to CFA greater than grade 3[Evaluated for toxicity at D1 of each cycle (every 42 days) and upon occurrence of an SAE.. ]
- Secondary Outcome Measures
Name Time Method To assess the antitumour effect of CFA per immune related response to criteria.<br>Target lesions will be measured at baseline and measured and recorded at each clinic visit. Imaging will be performed every 2 cycles (2x42 days). Response and progression will be evaluated using RECIST 1.1 guideline for immunotherapy.[Assessment on day 1 of each cycle (42 days)]