A trial to evaluate MLN0264 for the treatment of tumors of the stomach or the junction between the esophagus and the stomach and which have a protein called Guanylyl Cyclase C (GCC) present, in patients that have been treated previously but who have relapsed or in whom the cancer has spread.

• Register: EUCTR
• Last refreshed on: 8 February 2016
• Main ID: EUCTR2014-000804-88-BE
• Date of registration: 28/08/2014
• Prospective Registration: Yes
• Primary sponsor: Millennium Pharmaceuticals, Inc.
• Public title: A trial to evaluate MLN0264 for the treatment of tumors of the stomach or the junction between the esophagus and the stomach and which have a protein called Guanylyl Cyclase C (GCC) present, in patients that have been treated previously but who have relapsed or in whom the cancer has spread.
• Scientific title: A Phase 2 Trial of MLN0264 in Previously Treated Patients With Metastatic or Recurrent Adenocarcinoma of the Stomach or Gastroesophageal Junction Expressing Guanylyl Cyclase C (GCC)
• Date of first enrolment: 20/01/2015
• Target sample size: 81
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000804-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Belgium, Brazil, Italy, Peru, Spain, United Kingdom, United States

Contacts

• Name: Drug Information Call Center
• Affiliation: Millennium Pharmaceuticals, Inc.

• Name: Drug Information Call Center
• Affiliation: Millennium Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Each patient must meet all the following inclusion criteria to be enrolled in the study:

1. Male or female patients 18 years of age or older when written informed consent is obtained.

2. Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the stomach or gastroesophageal junction with IHC evidence of GCC expression indicated by an H-score of 10 or greater.

3. Treatment with 1 or more prior chemotherapies for advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.

4. Measurable disease as defined by RECIST version 1.1 guidelines.

5. ECOG performance status of 0 or 1 within 14 days before enrollment.
6. Female patients who:

- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR

- If they are of childbearing potential, agree to practice 2 effective methods ofcontraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)

Male patients, even if surgically sterilized (ie, status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)

7. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

8. Adequate organ and hematological function as evidenced by the following laboratory values within 14 days before enrollment:
- Absolute neutrophil count (ANC) = 1.5 x109/L
- Platelet count = 100 x 109/L
- Hemoglobin = 9 g/dL
- Activated partial thromboplastin time (aPTT) = 1.5 x the upper limit of the normal range (ULN) per institutional laboratory normal range
- International normalized ratio (INR) = 1.5 x ULN
- Serum creatinine = 1.5 x ULN
- Total bilirubin = 1.5 x ULN
- Albumin = 3g/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN
- Serum lipase = 3 x ULN and serum amylase within the normal range

9. Resolution of all toxic effects of prior treatments except alopecia to Grade 0 or 1 by NCI CTCAE version 4.03.

10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial 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 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

Exclusion criteria:
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

1. Radiotherapy within 4 weeks before enrollment

2. Concurrent treatment or treatment within 4 weeks of study entry with any other investigational agent or chemotherapy

3. Female patients who are lactating and breastfeeding or have a positive pregnancy test during the Screening period

4. Uncontrolled, clinically significant, symptomatic cardiovascular disease within 6 months before enrollment, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient
medication

5. Treatment with any medication that has a clinically relevant potential risk of prolonging the QT interval or inducing torsades de pointes that cannot be discontinued or switched to a different medication before starting study drug

6. Patients with ECG abnormalities considered by the investigator to be clinically significant, or repeated baseline prolongation of the rate-corrected QT interval (QTc)

7. Ongoing or clinically significant active infection as judged by the investigator

8. Signs of PN = NCI CTCAE Grade 2

9. Concomitant chemotherapy, hormonal therapy, immunotherapy, or any other form of cancer treatment

10. Use of strong cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks before the first dose of study drug

11. Any preexisting medical condition of sufficient severity to prevent full compliance with the study

12. History of or current neoplasm other than gastric adenocarcinoma, except for curatively treated nonmelanoma skin cancer or in situ carcinoma of the cervix uteri

13. Known diagnosis of human immunodeficiency virus (HIV) infection

14. Symptomatic brain metastases

15. Ongoing anticoagulant therapy (eg, aspirin, coumadin, heparin)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic or Recurrent Adenocarcinoma of the Stomach or Gastroesophageal Junction Expressing Guanylyl Cyclase C (GCC)
MedDRA version: 17.0 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 100000004864
MedDRA version: 17.0 Level: LLT Classification code 10001158 Term: Adenocarcinoma gastric stage IV with metastases System Organ Class: 100000004864
MedDRA version: 17.0 Level: LLT Classification code 10001152 Term: Adenocarcinoma gastric recurrent System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MLN0264
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Not applicable at this stage
CAS Number: 1514889-12-3
Current Sponsor code: MLN0264
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 180-

Primary Outcome(s)

Main Objective: To evaluate the overall response rate of patients with recurrent or metastatic GCC-positive adenocarcinoma of the stomach or gastroesophageal junction treated with MLN0264

Primary end point(s): ORR (complete response [CR] + PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary Objective: - To evaluate the safety profile of MLN0264
- To evaluate progression-free survival (PFS)
- To evaluate duration of response
- To evaluate disease control rate
- To evaluate overall survival
- To examine the pharmacokinetic profile
- To evaluate tumor size reduction
- To investigate the association between GCC expression level and antitumor effects of MLN0264
- To assess immunogenicity of MLN0264

Timepoint(s) of evaluation of this end point: Screening, Day 21 of every other cycle starting with Cycle 2 (ie, Cycles 2, 4, 6, etc.), at EOT, and during Progression Free Survival Follow-up (PFSFU).

Secondary Outcome(s)

Secondary end point(s): -AEs, serious adverse events (SAEs), clinical laboratory values, and vital sign measurements
- Efficacy Endpoints: PFS, DOR, DCR, including CR + PR + SD with minimum 12 weeks duration, OS, Tumor size reduction
- PK parameters
- - GCC H-score assessed by immunohistochemistry (IHC)
- Assessment of antitherapeutic antibodies (ATA)

Timepoint(s) of evaluation of this end point: AEs: From the first dose of study drug to 30 days after the last
dose.

SAEs: From the signing of the ICF to 30 days after the last dose

Clinical laboratory values: Day 1, Day 15 Cycle 1&2; Day 1 Cycle 3+; EoT.

Vital sign measurements: Screening; Day 1 at 5 and 15 minutes after the start of infusion and upon completion of the infusion for all cycles; EoT.

Efficacy Endpoints: Screening; Day 21 of every other cycle starting with Cycle 2 (ie, Cycles 2, 4, 6, etc.); EOT, and during PFSFU.

PK parameters: Specified timepoints on Day 1 all cycles; Day 3, Day 4, Day 8 & Day 15 Cycles 1 to 3; Day 4 & Day 8 Cycle 6; EoT.

GCC H-score assessed by immunohistochemistry (IHC): pre-screening.

Assessment of antitherapeutic antibodies (ATA): day 1 pre-dose; EoT.

Secondary ID(s)

2014-000804-88-IT

C26002

Source(s) of Monetary Support

Millennium Pharmaceuticals Inc