Treatment with Anlotinib for patients with metastatic or advanced rare type of sarcoma (soft tissue cancer)

Phase 1

• Conditions: Alveolar soft part sarcoma, Leiomyosarcoma and Synovial sarcoma; MedDRA version: 21.1Level: PTClassification code 10001884Term: Alveolar soft part sarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10024191Term: Leiomyosarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10042864Term: Synovial sarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001655-31-GB
• Lead Sponsor: Advenchen Laboratories LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-08
• Last Update Posted: 21 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 325

Inclusion Criteria

1. Patients who are able to sign inform consent
2. Male or female at least 18 years of age
3. Indication A – ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma.
Indication C – SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma.
Indication D – LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin).
4. Indication A – ASPS: Subjects with or without prior therapy.
Indication C – SS: Subjects previously treated with at least one prior line of standard systemic therapy, including first-line anthracycline containing regimen
Indication D – LMS: Treatment of patients with metastatic or advanced leiomyosarcoma (LMS) who have failed at least one prior line of standard therapy and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment.
5. Show clinical or objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability within 6 months of enrollment
6. ECOG 0 or 1
7. Measurable disease as per RECIST 1.1
8. Life expectancy of at least 3 months
9. Female of childbearing potential - negative test at screening and male and female participants willing to use contraception
10. Adequate hematologic, hepatic and renal function as assessed by the following laboratory requirements conducted within 28 days of enrollment
11. Left ventricular ejection fraction (LVEF) of > 50% by ECHO or MUGA within 56 days of enrollment
12. Two readings of systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg at screening taken at least 5 minutes apart in the sitting position after 5 minutes of rest.
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 268
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 57

Exclusion Criteria

1. Prior treatment with or have known hypersensitivity to AL3818
2. Indication A – ASPS: Prior treatment with cediranib
Indication C – SS: Prior treatment with or have known hypersensitivity to dacarbazine.
Indication D – LMS: Prior treatment with anlotinib.
3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS, LMS, or SS within 5 years before enrollment except for successfully treated in situ carcinoma, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and T1).
4. Received last dose of systemic cytotoxic therapy or investigational therapy within 21 days of enrollment or last dose of hormonal therapy, immunotherapy, targeted therapy or any other type of non-cytotoxic anti-cancer therapy within 14 days of enrollment.
5. Prior treatment with extended-field radiotherapy (EFRT) within 28 days of enrollment or prior treatment with any other form of radiotherapy within 14 days of enrollment.
6. Known active CNS metastases and/or carcinomatous meningitis. Patients with brain mets who are stable can be considered.
7. Cavitary tumors or tumors invading or abutting large blood vessels in the thorax.
8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess within 6 months of enrollment.
9. Known history of bleeding disorders
10. Clinically significant bleeding
11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of bleeding within 28 days prior to enrollment
12. History of untreated deep venous thrombosis (DVT) within the past 6 months
13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study treatment
14. Serious non-healing wound, active ulcer
15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or minor surgical procedure within 7 days of enrollment
16. CTCAE version 4.03 > grade 3 peripheral neuropathy
17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any previous therapy
18. QTcF > 470 msec (per Fridericia’s formula) on electrocardiogram within 28 days of enrollment
19. Severe and uncontrolled disease: Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class 2 or above congestive heart failure; active serious infections; liver diseases; renal failure; poorly controlled diabetes; untreated or uncontrolled epileptic seizures; drug abuse; untreated psychiatric disorders
20. HIV positive
21. Had organ transplant
22. Not able to take oral medications
23. Females who are pregnant or are breast-feeding
24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5; or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and CYP2C19; or QT prolongating medications within 14 days prior to enrollment and during the study unless there was an emergent or life-threatening medical condition that required it.
25. Any medical intervention that will exclude patients based on investigator assessment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified