Alveolar Soft Part SarcomaPhase 3APROMISSNCT03016819
Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS)
A Phase 3 study testing AL3818, Dacarbazine and Midazolam 2 mg for CYP3A4 phenotyping in people with Alveolar Soft Part Sarcoma and Leiomyosarcoma, run by Advenchen Laboratories, LLC at 24 sites in 5 countries.
Trial summary
THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA. This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma
- What is being tested?
- AL3818, Dacarbazine and Midazolam 2 mg for CYP3A4 phenotyping
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 325 participants
- Where
- 24 sitesin 5 countries
- Study dates
- 15 Aug 2017to Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent provided before any study-specific procedures are initiated. Subject must be able to understand and be willing to sign a written informed consent form.
- Male or female at least 18 years of age.
- a. Indication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma. b. CLOSED Indication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone). c. CLOSED Indication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma. d. CLOSED Indication D - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin).
- 3. Open Indication E: Any sarcomas or other solid tumors 4. a. Indication A - ASPS: Subjects with or without prior therapy. b. Indications B - LMS: Subjects previously treated with at least one prior line of approved therapy. (New Recruitment Suspended) c. Indication C - SS: Subjects previously treated with at least one prior line of standard systemic therapy, including first-line anthracycline containing regimen (except if medically contraindicated or refused by subject). d. 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. Patients must have received and progressed on prior therapy and have been treated any line with an anthracycline. e. Indication E: Any sarcomas or other solid tumors such as NSCLC, SCLC and Thyroid cancer etc.: Subjects exhausted SOC treatment or refuse for any SOC 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 (excluding ASPS subjects who have not received prior therapy).
- 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by CT or MRI scan of the chest, abdomen and pelvis (and other areas of disease) within 28 days prior to enrollment. 8. Life expectancy of at least 3 months.
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- 9. Females of childbearing potential must have a negative pregnancy test (by serum beta- HCG) within 7 days prior to the start of treatment.
- 10. Female of childbearing potential must be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the investigator), or agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 2 years. Males must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) at the discretion of the investigator. 11. Adequate hematologic, hepatic and renal function as assessed by the following laboratory requirements conducted within 28 days of enrollment:
- Total bilirubin < the upper limit of normal (ULN), unless the patient has documented Gilbert's disease for which the total bilirubin should be < 3. b. Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x of ULN for subjects with liver involvement of their cancer) c. Amylase and lipase < 1.5 x of ULN d. Serum creatinine < 1.5 x of ULN e. Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min (Cockcroft and Gault) or by 24 hour urine collection. f. International normalize ratio (INR) and the activated partial thromboplastin time (aPTT/PTT) < 1.5 x ULN. (Subjects who are therapeutically treated with an agent such LMWH or heparin will be allowed to participate provided that no prior evidence of an underlying abnormality in coagulation parameters exists) g. Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil count > 1,500 cells/mm3 h. Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver involvement of their cancer) i. Urine protein < 30 mg/dL. If urine protein is > 30 mg/dL, a 24-hour urine collection will be required and must show total protein excretion <1,000 mg per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0.
- 12. Left ventricular ejection fraction (LVEF) of > 50% by ECHO or MUGA within 56 days of enrollment. 13. 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. Subjects with well managed hypertension who are on oral antihypertensives must be on their current medication(s) and stable dose(s) for at least 2 weeks prior to enrollment.
Who cannot join
- Prior treatment with or have known hypersensitivity to AL3818.
- a. Indication A - ASPS: Prior treatment with cediranib. b. Indication B - LMS: Prior treatment with or have known hypersensitivity to dacarbazine. (New Recruitment Suspended) c. Indication C - SS: Prior treatment with or have known hypersensitivity to dacarbazine.
- Indication D - LMS: Prior treatment with anlotinib.
- 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).
- 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.
- 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.
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- Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided that they are stable with no evidence of progression by imaging, and all neurologic symptoms have returned to baseline, and should not be using corticosteroids for at least 7 days prior to study treatment.
- Cavitary tumors or tumors invading or abutting large blood vessels in the thorax.
- History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess within 6 months of enrollment.
- Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).
- Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to enrollment.
- CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of bleeding within 28 days prior to enrollment.
- History of untreated deep venous thrombosis (DVT) within the past 6 months. Patients with recent DVT who are treated with therapeutic anti-coagulating agents (excluding therapeutic warfarin which is exclusionary) for at least 14 days prior to start of study treatment.
- Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study treatment.
- The use of prophylactic therapeutic anti-coagulants are allowed provided that INR or aPTT are within therapeutic limits (according to the medical standard of the enrollment institution) and patient has been on a stable dose of anticoagulants for at least two weeks prior to the first dose of study treatment.
- Serious non-healing wound, active ulcer.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or minor surgical procedure within 7 days of enrollment.
- CTCAE version 4.03 > grade 3 peripheral neuropathy
- Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any previous therapy (excluding alopecia and neurotoxicity < grade 2)
- QTcF > 470 msec (per Fridericia's formula) on electrocardiogram within 28 days of enrollment.
- Severe and uncontrolled disease, including:
- Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class 2 or above congestive heart failure classified according to New York Heart Association (NYHA)
- Active or failed to control serious infections (CTCAE version 4.03 > grade 2 infections)
- Liver disease such as cirrhosis of the liver, decompensated liver disease, chronic active hepatitis needing anti-viral therapy
- Renal failure needing hemodialysis or peritoneal dialysis
- Poorly controlled diabetes (HgA1C >8)
- Untreated and uncontrolled epileptic seizures
- History of psychotropic drug abuse and inability to quit
- Untreated psychiatric disorders
- Known HIV-positive
- Had organ transplantation
- Clinical conditions affecting the intake and use of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction)
- Females who are pregnant or are breast-feeding.
- 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.
- Any medical intervention, condition or any other circumstance which in the opinion of the investigator or the sponsor's medical monitor, could compromise adherence to study procedures or study objectives.
Trial locations and contacts
24 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
24 sites in 5 countries
United States17 sites, 1 recruiting
- Completed
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
- Completed
University of Colorado Denver
Aurora, Colorado, 80045
- Completed
Northwestern University
Chicago, Illinois, 60611
- Completed
MD Anderson Cancer Center
Houston, Texas, 77030
- Completed
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
- Completed
University of California Los Angeles
Los Angeles, California, 90404
- Completed
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
- Completed
Vanderbilt University
Nashville, Tennessee, 37203
- Withdrawn
Columbia University Medical Center
New York, New York, 10032
- Completed
Thomas Jefferson Hospital - Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
- Completed
Mayo Clinic Arizona
Phoenix, Arizona, 85054
- Completed
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15219
- Completed
Mayo Clinic Rochester
Rochester, Minnesota, 55905
- Recruiting
Sarcoma Oncology Center
Santa Monica, California, 90403
Victoria Study Coordinator, vchua@sarcomaoncology.com
Sant P Chawla, MD
- Completed
UW Medicine-Seattle Cancer Care Alliance
Seattle, Washington, 98109
- Completed
Washington University St. Louis
St Louis, Missouri, 63130
- Completed
Stanford Medicine Cancer Institute
Stanford, California, 94305
Italy3 sites
- Completed
Istituto Nazionale dei Tumori
Milan
- Completed
University of Palermo
Palermo
- Completed
University Campus Bio-Medico
Rome
China2 sites
- Completed
Beijing Cancer Hospital
Beijing
- Completed
Shanghai Sixth People's Hospital
Shanghai
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Royal Marsden Hospital
London, SW3 6JJ
Thuy Study Coordinator, Thuy-Giang.Nguyen@nhs.net
Robin Jones, MD
About this study
Official title: A Phase III Study of AL3818 (Anlotinib, Catequentinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma
THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA.
This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.
Read the detailed description
THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA.
APROMISS is a phase 3 study evaluating the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). Population pharmacokinetics and exploratory exposure-response analyses will also be conducted in subjects receiving AL3818.
Indication A: 56 subjects with metastatic or advanced ASPS not amenable to surgical resection will receive open-label AL3818 at a dose of 12 mg once daily in 21-day cycles (14 days on treatment, 7 days off treatment) until disease progression (defined by RECIST version 1.1) ot unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoint is duration of response (DOR). - CLOSED
Indication B: 68 subjects with metastatic or advanced LMS who have failed at least one prior line of approved therapy will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Indication C: 95 subjects with with metastatic or advanced SS who have failed at least one prior line of approved therapy, including first-line anthracycline-containing chemotherapy, will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Indication D - LMS: 106 subjects with histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin who have failed at least one prior line of standard therapy (including anthracycline-based therapy) and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment will be enrolled. Subjects will be randomized with a 2:1 ratio to receive either blinded AL3818 or placebo with approximately 71 subjects in the AL3818 group and 35 subjects in the placebo group until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to placebo will have the option to crossover and receive AL3818 at the time of documented disease progression (and after crossover unblinding). The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
In indication E-- A total sample size of 25 subjects will be enrolled to collect baseline PK and ECG data. A total of 18 patients are projected to complete collecting fourth cycle (C4) PK and ECG data. This C-QTc study will assess the potential for cardiac repolarization delays following administration of catequentinib hydrochloride. This assessment involves examination of the QT interval at the drug concentrations of baseline and fourth cycle of steady state which was concluded by population PK results.
Catequentinib hydrochloride is a strong Cytochrome enzyme P450 3A4 (CYP3A4) inhibitor and mild inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) based on the in vitro assay. This designed DDI study will assess how catequentinib hydrochloride affects the pharmacokinetics (PK) of midazolam (a known probe substrate of CYP3A4), Digoxin (a known probe substrate of P-gp) and rosuvastatin (a known probe substrate of BCRP) after the treatments of fourth cycles.
- Being tested
- AL3818, Dacarbazine, AL3818 or placebo, Midazolam 2 mg for CYP3A4 phenotyping, Digoxin (0.25mg)
- Medical subject headings
- Sarcoma, Alveolar Soft Part, Leiomyosarcoma, Sarcoma, Synovial, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL3818Drug
Also called Catequentenib, Anlotinib
Anlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
DacarbazineDrug
Also called DTIC
Dacarbazine 1000 mg/m2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle
AL3818 or placeboDrug
AL3818 or placebo 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
Midazolam 2 mg for CYP3A4 phenotypingDrug
In indication E, midazolam will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of Cytochrome enzyme P450 3A4 (CYP3A4).
Digoxin (0.25mg)Drug
In indication E, Digoxin will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of P-glycoprotein.
Rosuvastatin 10 mg tablet.Drug
In indication E, Rosuvastatin will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of breast cancer resistance protein .
| Study group | Role | What they receive |
|---|---|---|
| Indication A: ASPS AL3818 Arm - CLOSED | Experimental | All subjects with ASPS will be assigned to the open-label AL3818 arm to receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). Receives: Drug: AL3818 |
| Indication B: LMS AL3818 Arm - CLOSED | Experimental | Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). Receives: Drug: AL3818 |
| Indication B: LMS Dacarbazine Arm - CLOSED | Active comparator | Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle. Receives: Drug: Dacarbazine |
| Indication C: SS AL3818 Arm - CLOSED | Experimental | Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). Receives: Drug: Dacarbazine |
| Indication C: SS Dacarbazine Arm - CLOSED | Experimental | Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle. Receives: Drug: Dacarbazine |
| Indication D: LMS AL3818 or Placebo Arm - CLOSED | Placebo comparator | Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or placebo in a double-blind manner. AL3818 or placebo will be administrated as one 12 mg capsule orally once daily in 21-day cycles for 14 days on treatment (Days 1-14) and 7 days off treatment (Days 15-21). Receives: Drug: AL3818 or placebo |
| Indication E: Catequentinib Hydrochloride (AL3818) Study of Concentration-QTc (C-QTc) and Drug-Drug | Active comparator | This designed DDI study will assess how catequentinib hydrochloride affects the pharmacokinetics (PK) of midazolam (a known probe substrate of CYP3A4), Digoxin (a known probe substrate of P-gp) and rosuvastatin (a known probe substrate of BCRP) after the treatments of fourth cycles. Receives: Drug: AL3818; Drug: Midazolam 2 mg for CYP3A4 phenotyping; Drug: Digoxin (0.25mg); Drug: Rosuvastatin 10 mg tablet. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) (ASPS)
To determine ORR in subjects with ASPS, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).
Measured: Up to 48 months
Progression Free Survival (PFS) (LMS/SS)
To compare PFS in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined a median number of months from the date of randomization until the first documented sign of disease progression or death due to any causes, whichever occurs earlier as evaluated by a blinded independent radiologic review (BICR).
Measured: From time of randomization to the date of disease progression or death from any cause, up to 48 months
Assess the ECG and the PK parameters of catequentinib hydrocoloride in probe substance (Indication E)
To assess the ECGs and the PK parameters of catequentinib hydrocoloride in the administration of single-dose midazolam and single-dose of combined administration of P-gp and BCRP substrates digoxin and rosuvastatin in cancer patients.
Measured: Each patient study duration is designed to end between C4D18-D21 when the first RECIST and final visit are planned. Whole study duration is approximately 12 months and no any follow up is planned
Secondary outcomes (2)
Duration of Response (DOR) (ASPS)
To determine DOR in subjects with ASPS, defined as median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes
Measured: Up to 48 months
Objective Response Rate (ORR) (LMS/SS)
To compare ORR in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2017 (estimated)
- Study start15 Aug 2017
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alveolar Soft Part SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 325 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Advenchen Laboratories, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul CEO, Study director, Advenchen Laboratories, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03016819
- Sponsor's protocol ID
- AL3818-US-004
- Acronym
- APROMISS
- Status last verified
- Feb 2026
- First submitted
- 6 Jan 2017
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study of AL3818 (Anlotinib, Catequentinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma
- ClinicalTrials.gov ID
- NCT03016819
- Acronym / sponsor ID
- APROMISS / AL3818-US-004
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 325 participants (estimated)
- Lead sponsor
- Advenchen Laboratories, LLCIndustry (pharma, biotech, devices)
- Study start
- 15 Aug 2017 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 11 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA.
This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.
Detailed description
THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA.
APROMISS is a phase 3 study evaluating the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). Population pharmacokinetics and exploratory exposure-response analyses will also be conducted in subjects receiving AL3818.
Indication A: 56 subjects with metastatic or advanced ASPS not amenable to surgical resection will receive open-label AL3818 at a dose of 12 mg once daily in 21-day cycles (14 days on treatment, 7 days off treatment) until disease progression (defined by RECIST version 1.1) ot unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoint is duration of response (DOR). - CLOSED
Indication B: 68 subjects with metastatic or advanced LMS who have failed at least one prior line of approved therapy will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Indication C: 95 subjects with with metastatic or advanced SS who have failed at least one prior line of approved therapy, including first-line anthracycline-containing chemotherapy, will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Indication D - LMS: 106 subjects with histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin who have failed at least one prior line of standard therapy (including anthracycline-based therapy) and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment will be enrolled. Subjects will be randomized with a 2:1 ratio to receive either blinded AL3818 or placebo with approximately 71 subjects in the AL3818 group and 35 subjects in the placebo group until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to placebo will have the option to crossover and receive AL3818 at the time of documented disease progression (and after crossover unblinding). The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
In indication E-- A total sample size of 25 subjects will be enrolled to collect baseline PK and ECG data. A total of 18 patients are projected to complete collecting fourth cycle (C4) PK and ECG data. This C-QTc study will assess the potential for cardiac repolarization delays following administration of catequentinib hydrochloride. This assessment involves examination of the QT interval at the drug concentrations of baseline and fourth cycle of steady state which was concluded by population PK results.
Catequentinib hydrochloride is a strong Cytochrome enzyme P450 3A4 (CYP3A4) inhibitor and mild inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) based on the in vitro assay. This designed DDI study will assess how catequentinib hydrochloride affects the pharmacokinetics (PK) of midazolam (a known probe substrate of CYP3A4), Digoxin (a known probe substrate of P-gp) and rosuvastatin (a known probe substrate of BCRP) after the treatments of fourth cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Indication A: ASPS AL3818 Arm - CLOSED | Experimental | Drug: AL3818All subjects with ASPS will be assigned to the open-label AL3818 arm to receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). |
| Indication B: LMS AL3818 Arm - CLOSED | Experimental | Drug: AL3818Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). |
| Indication B: LMS Dacarbazine Arm - CLOSED | Active comparator | Drug: DacarbazineSubjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle. |
| Indication C: SS AL3818 Arm - CLOSED | Experimental | Drug: DacarbazineSubjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). |
| Indication C: SS Dacarbazine Arm - CLOSED | Experimental | Drug: DacarbazineSubjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle. |
| Indication D: LMS AL3818 or Placebo Arm - CLOSED | Placebo comparator | Drug: AL3818 or placeboSubjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or placebo in a double-blind manner. AL3818 or placebo will be administrated as one 12 mg capsule orally once daily in 21-day cycles for 14 days on treatment (Days 1-14) and 7 days off treatment (Days 15-21). |
| Indication E: Catequentinib Hydrochloride (AL3818) Study of Concentration-QTc (C-QTc) and Drug-Drug | Active comparator | Drug: AL3818, Drug: Midazolam 2 mg for CYP3A4 phenotyping, Drug: Digoxin (0.25mg), Drug: Rosuvastatin 10 mg tablet.This designed DDI study will assess how catequentinib hydrochloride affects the pharmacokinetics (PK) of midazolam (a known probe substrate of CYP3A4), Digoxin (a known probe substrate of P-gp) and rosuvastatin (a known probe substrate of BCRP) after the treatments of fourth cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent provided before any study-specific procedures are initiated. Subject must be able to understand and be willing to sign a written informed consent form.
- Male or female at least 18 years of age.
- a. Indication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma. b. CLOSED Indication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone). c. CLOSED Indication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma. d. CLOSED Indication D - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin).
- 3. Open Indication E: Any sarcomas or other solid tumors 4. a. Indication A - ASPS: Subjects with or without prior therapy. b. Indications B - LMS: Subjects previously treated with at least one prior line of approved therapy. (New Recruitment Suspended) c. Indication C - SS: Subjects previously treated with at least one prior line of standard systemic therapy, including first-line anthracycline containing regimen (except if medically contraindicated or refused by subject). d. 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. Patients must have received and progressed on prior therapy and have been treated any line with an anthracycline. e. Indication E: Any sarcomas or other solid tumors such as NSCLC, SCLC and Thyroid cancer etc.: Subjects exhausted SOC treatment or refuse for any SOC 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 (excluding ASPS subjects who have not received prior therapy).
Key exclusion criteria (35 listed)
- Prior treatment with or have known hypersensitivity to AL3818.
- a. Indication A - ASPS: Prior treatment with cediranib. b. Indication B - LMS: Prior treatment with or have known hypersensitivity to dacarbazine. (New Recruitment Suspended) c. Indication C - SS: Prior treatment with or have known hypersensitivity to dacarbazine.
- 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).
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AL3818Also: Catequentenib, AnlotinibAnlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment) | Drug | Indication A: ASPS AL3818 Arm - CLOSED, Indication B: LMS AL3818 Arm - CLOSED, Indication E: Catequentinib Hydrochloride (AL3818) Study of Concentration-QTc (C-QTc) and Drug-Drug |
| DacarbazineAlso: DTICDacarbazine 1000 mg/m2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle | Drug | Indication B: LMS Dacarbazine Arm - CLOSED, Indication C: SS AL3818 Arm - CLOSED, Indication C: SS Dacarbazine Arm - CLOSED |
| AL3818 or placeboAL3818 or placebo 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment) | Drug | Indication D: LMS AL3818 or Placebo Arm - CLOSED |
| Midazolam 2 mg for CYP3A4 phenotypingIn indication E, midazolam will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of Cytochrome enzyme P450 3A4 (CYP3A4). | Drug | Indication E: Catequentinib Hydrochloride (AL3818) Study of Concentration-QTc (C-QTc) and Drug-Drug |
| Digoxin (0.25mg)In indication E, Digoxin will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of P-glycoprotein. | Drug | Indication E: Catequentinib Hydrochloride (AL3818) Study of Concentration-QTc (C-QTc) and Drug-Drug |
| Rosuvastatin 10 mg tablet.In indication E, Rosuvastatin will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of breast cancer resistance protein . | Drug | Indication E: Catequentinib Hydrochloride (AL3818) Study of Concentration-QTc (C-QTc) and Drug-Drug |
Primary outcome
Objective Response Rate (ORR) (ASPS)
Time frame: Up to 48 months
To determine ORR in subjects with ASPS, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).
Progression Free Survival (PFS) (LMS/SS)
Time frame: From time of randomization to the date of disease progression or death from any cause, up to 48 months
To compare PFS in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined a median number of months from the date of randomization until the first documented sign of disease progression or death due to any causes, whichever occurs earlier as evaluated by a blinded independent radiologic review (BICR).
Assess the ECG and the PK parameters of catequentinib hydrocoloride in probe substance (Indication E)
Time frame: Each patient study duration is designed to end between C4D18-D21 when the first RECIST and final visit are planned. Whole study duration is approximately 12 months and no any follow up is planned
To assess the ECGs and the PK parameters of catequentinib hydrocoloride in the administration of single-dose midazolam and single-dose of combined administration of P-gp and BCRP substrates digoxin and rosuvastatin in cancer patients.
2 secondary outcomes
Duration of Response (DOR) (ASPS)
Time frame: Up to 48 months
Objective Response Rate (ORR) (LMS/SS)
Time frame: Up to 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul CEO study director
Advenchen Laboratories, LLC
24 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AL3818, Dacarbazine and Midazolam 2 mg for CYP3A4 phenotyping in people with Alveolar Soft Part Sarcoma and Leiomyosarcoma, run by Advenchen Laboratories, LLC at 24 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Italy, China, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shiying Clinical Trial Manager (8055301550, Shiyings@advenchen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (ASPS) (time frame: Up to 48 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.