A dose escalation and expansion study of XMT-1536 en patients with solid tumors.
- Conditions
- High grade serous ovarian cancerMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000630-17-PL
- Lead Sponsor
- Mersana Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 240
For Dose Escalation, Expansion and Uplift
1. Females and males, aged =18 years old
2. ECOG performance status 0 or 1
3. Measurable disease as per RECIST, version 1.1
4. Resolution of all acute toxic effects of prior therapy or surgical procedures to =Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on =10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy)
5. Cardiac left ventricular ejection fraction (LVEF) =50% or = the institution’s lower limit of normal by either Echo or MUGA scan
6. Adequate organ function as defined by the following criteria:
a. Absolute neutrophil count (ANC) =1500 cells/mm3
b. Platelet count =100,000/mm3
c. Hemoglobin =9 g/dL
d. INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institutional upper limit of normal (ULN) in the absence of any other indicator of liver dysfunction. Patients on anticoagulants are allowed.
e. Estimated glomerular filtration rate (GFR) =45 mL/min
f. Total bilirubin =ULN
Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia may be eligible after discussion with the Sponsor Medical Monitor.
7. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) =1.5 times the institutional ULN. Alkaline phosphatase (ALP) =1.5 times ULN unless clearly attributable to a non-hepatic source, e.g., bone metastasis.
8. Albumin =3.0 g/dL
9. Female participants of child-bearing potential must use a highly effective non-hormonal form of contraception for the duration of study drug administration and for at least 6 months after the last dose of study drug.
Examples of non-hormonal highly effective contraceptive methods include:
a) intrauterine device (IUD); b) bilateral tubal occlusion; c) vasectomized partner; d) female sterilization; e) sexual abstinence. Sexual Abstinence is defined by refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence shall be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the study patient. Periodic abstinence (calendar, symptom-thermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Male study participants must use barrier contraception (condoms) for the duration of study drug and for at least 6 months after the last dose of study drug. The WOCBP partners of male study participants must use highly effective contraception for the duration of study drug and for at least 6 months after the last dose of study drug
10. Able to provide informed consent
for UPLIFT
1. Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent
2. Platinum-resistant disease
a. Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and = 6 months after the date of the last dose of platinum
b. Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles o
For Dose Escalation, Expansion and Uplift
1. Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity (consultation with the Sponsor Medical Monitor is recommended).
2. Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
a. Patients are eligible if CNS metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to enrollment.
b. In addition, patients must be either off corticosteroids, or on a stable/decreasing dose of = 10 mg daily prednisone (or equivalent). Anticonvulsants are allowed except for those drugs associated with liver toxicity.
3. Untreated known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). In addition, negative serology is required during screening (baseline) for HBV and HCV:
a. HBV: Patients with serologic evidence of chronic HBV infection should have an HBV viral load below the limit of quantification to be eligible.
b. HCV: Patients with a history of HCV infection should have completed curative antiviral treatment and HCV viral load below the limit of quantification.
c. HIV: screening for HIV is not required except if mandated by local regulations.
4. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations. Further, patients are excluded with the following characteristics:
a. A marked baseline prolongation of QT/QTc interval using Frederica's QT correction formula.
b. A history of additional risk factors for Torsade's de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
c. The use of concomitant medications that prolong the QT/QTc interval will be reviewed first with the Sponsor Medical Monitor.
5. History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease. FibroScan testing may be required for patients with a history of chronic liver disease, e.g., fatty liver.
6. Patients cannot receive drugs associated with hepatotoxicity concurrent with XMT-1536 administration. Patients may receive acetaminophen/paracetamol for a limited time but at a total daily dose of =2 g per day. Use of NSAIDs or steroids for treatment of fever is encouraged.
7. Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
8. Currently active pneumonitis, interstitial lung disease, or a history of Grade = 2 pneumonitis within the last 12 months that required medical intervention such as treatment with corticosteroids
9. Pregnant or nursing women
10.Diagnosis of additional malignancy that required treatment within 2 years prior to screening, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix
11. Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
12. Use of strong CYP450 inhibitors
Ovarian Cancer Exclusion Criteria for UPLIFT – Cohort
1. Low-grade, clear cell, endometrioid,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method