A Phase 1/2a/3 Evaluation of the Safety and Efficacy of Adding AL3818 (Anlotinib, INN: Catequentinib), a Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma
- Conditions
- Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancerMedDRA version: 21.1Level: LLTClassification code 10003758Term: Atypical proliferating ovarian tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-003871-32-IT
- Lead Sponsor
- ADVENCHEN LABORATORIES, LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 270
1. Female = 18 years of age
2. Histologically proven diagnosis of:
Phase III/Part 3:
(1) Platinum-resistant (progression within 6 months after last platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer that meets one of the following criteria:
i. Subject has received at least two prior lines of systemic therapy including a bevacizumab-containing regimen as standard of care
ii. Subject has received at least two prior lines of systemic therapy, has not received a prior bevacizumab-containing regimen and is not eligible for a bevacizumab containing regimen based on Investigator’s assessment
(2) Platinum-refractory (progression during first-line platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer after at least one prior line of systemic therapy
(3) For groups 1-2 above: Subjects with positive deleterious or suspected deleterious, germline or somatic BRCA mutated status must have received a PARP inhibitor as a prior line of therapy.
Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma
3. Have measurable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28 days of enrollment.
4. Life expectancy of = 3 months at the time of enrollment.
5. Able to take orally administered study medication.
6. Have adequate baseline function and performance status within 28 days of enrollment:
a. Bone marrow function: absolute neutrophil count (ANC) = 1,500/mm3, platelets =100,000/mm3
b. Renal function: creatinine = 1.5 x institutional upper limit normal (ULN) or if creatinine is >1.5 x ULN, creatinine clearance must be > 50 mL/min.
c. Hepatic function: bilirubin = 1.5 x ULN or = 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT = 3.0 × ULN.
d. Coagulation profile: international normalized ratio (INR) is = 1.5 and an aPTT or PTT <1.2 x ULN.
e. ECOG performance = 2
7. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy test within 28 days of enrollment.
8. Provide written informed consent and authorization permitting release of Protected Health Information.
9. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1. Serious, non-healing wound, ulcer or bone fracture
2. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to C1D1 (a major surgical procedure is defined as requiring general anesthesia).
3. (Intentionally left blank)
4. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
5. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic
attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment.
a. Subjects with metastatic CNS tumors may participate in this study if the subject is > 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid
therapy.
6. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or = 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine
protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study.
7. Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure
(Appendix E); serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease.
8. Women who are pregnant or nursing.
9. (Intentionally left blank)
10. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
11. Hemoptysis within 3 months prior to enrollment.
12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver dysfunction.
13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment.
14. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or lifethreatening medical condition that required it.
15. Known history of human immunodeficiency virus infection (HIV).
16. Active bacterial infections requiring systemic antibiotics (excluding uncomplicated urinary tract infection).
17. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy.
18. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product.
19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
20. Intra-abdominal abscess within the last 3 months of enrollment.
21. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP >160 mm Hg or diastolic BP >90 mm Hg pressure.
22. QT
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