Phase 1/2a Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)

Conditions:Ovarian Cancer, Cervical Cancer, Cancer, Women's Studies
Therapuetic Areas:Oncology, Reproductive
Age Range:18 - Any
Start Date:December 2015
End Date:December 2018
Contact:Judy Chen, Pharm.D.

Use our guide to learn which trials are right for you!

A Phase 1/2a Evaluation of the Safety and Efficacy of Adding AL3818, a Dual Receptor Tyrosine Kinase Inhibitor, to Standard Platinum-Based Chemotherapy, in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)

This trial is a Phase 1b/2a trial designed to evaluate the safety and efficacy of adding oral
AL3818 to standard platinum-based chemotherapy concurrently and continued as a maintenance
therapy for up to 12 months.

This trial is a Phase 1b/2a trial designed to evaluate the safety and efficacy of adding oral
AL3818 to standard platinum-based chemotherapy such as carboplatin plus paclitaxel,
concurrently and continued as a maintenance therapy for up to 12 months, in subjects with
recurrent or metastatic endometrial, ovarian, fallopian, primary peritoneal, or cervical
carcinoma. AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which
shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular
endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse
models, including various cancer xenografts, have demonstrated that treatment of
tumor-bearing mice with AL3818 induces tumor reductions.

This study will be divided into two parts. The objective of Part 1 is the evaluation of the
safety and tolerability of adding oral AL3818 to standard carboplatin plus paclitaxel
chemotherapy for a cycle of 21 days to determine the recommended Phase II dose (RP2D). The
objective of Part 2 is evaluation of preliminary efficacy and the safety of adding oral
AL3818 at the RP2D determined in Part 1 to carboplatin and paclitaxel chemotherapy for 6
cycles. Continuous maintenance mono therapy with 14 days on and 7 days off regimen at the
RP2D will be conducted up to 12 months and is extendable beyond until disease progression.

Inclusion Critera

1. Female ≥ 18 years of age

2. Histologically proven diagnosis of:

a. Endometrial and other uterine cancers with tumors of all histologies i. Recurrent
Stage I to II endometrial and other uterine cancers, after at least one prior line of
standard therapy, requiring further treatment with platinum-based chemotherapy ii.
Advanced Stage III to IV endometrial and other uterine cancers requiring treatment
with platinum-based chemotherapy b. Ovarian Cancer: Platinum-sensitive or
platinum-resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal
cancer treated with at least one prior line of platinum-based chemotherapy and
requiring further treatment.

Platinum-sensitive is defined as cancer progression ≥ 6 months after platinum-based
chemotherapy. Platinum-resistant is defined as cancer progression < 6 months after
platinum-based chemotherapy.

Histologic cell types eligible are endometrioid adenocarcinoma, serous adenocarcinoma,
undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma,
adenocarcinoma not otherwise specified. c. Cervical cancer: recurrent or metastatic
cervical cancer that is not amenable to curative treatment with surgery and/or
radiation therapy and has not been previously treated with chemotherapy for

Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or

3. Have measureable 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:

1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥

2. 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.

3. Hepatic function: bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for subjects with Gilbert
Syndrome; AST and ALT ≤ 3.0 × ULN.

4. Coagulation profile: international normalized ratio (INR) is ≤ 1.5 and an aPTT or
PTT < 1.2 x ULN

5. 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.

Exclusion Criteria

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

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

11. Hemoptysis within 3 months prior to enrollment.

12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver

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
life-threatening 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. QTc > 470 msec on screening ECG per Fridericia's formula.

23. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome).

24. Concurrent use of concomitant medications that prolong the QT/QTc interval.

25. Baseline echocardiogram (within 56 days of enrollment) with left ventricular ejection
fraction (LVEF) < 50%.

26. History of difficulty swallowing, malabsorption, active partial or complete bowel
obstruction, or other chronic gastrointestinal disease or condition that may hamper
compliance and/or absorption of AL3818.

27. History of pancreatitis; history of renal disease that includes histologically
confirmed glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal
nephropathy or other renal insufficiencies.

28. Treatment with an investigational agent within 28 days of enrollment.

29. Known recreational substance abuse.

30. Anticoagulation therapy with warfarin. Subjects treated with heparin, low molecular
weight heparin, or any other anticoagulant may be included provided the subject has
been on a stable therapeutic dose of the anticoagulant for at least 14 days prior to

31. Known hypersensitivity to AL3818 or components of the formulation.
We found this trial at
1475 NW 12th Ave
Miami, Florida 33136
(305) 243-1000
Principal Investigator: Marilyn Huang, MD
University of Miami, Sylvester Comprehensive Cancer Center Sylvester Comprehensive Cancer Center integrates all cancer-related activities...
Miami, FL
Click here to add this to my saved trials
Dallas, Texas 75231
Principal Investigator: David Miler, MD
Dallas, TX
Click here to add this to my saved trials
Long Beach, California
Principal Investigator: Eric M Cheung, DO
Long Beach, CA
Click here to add this to my saved trials
433 Bolivar Street
New Orleans, Louisiana 70112
Principal Investigator: Agustin Garcia, MD
New Orleans, LA
Click here to add this to my saved trials