A Study of MLN0264 in Patients With Cancer of the Stomach or Gastroesophageal Junction

Adenocarcinoma of the Stomach Clinical Trial

Official 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02202759
• Other study ID #: C26002
• Secondary ID: U1111-1155-90232
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 7, 2014
• Last updated: May 3, 2016
• Start date: July 2014
• Est. completion date: September 2018

Study information

• Verified date: December 2015
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Department of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySpain: Agencia Española de Medicamentos y Productos SanitariosItaly: The Italian Medicines AgencyBelgium: Federal Agency for Medicinal Products and Health ProductsPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPeru: Ministry of HealthEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy, safety and tolerability of MLN0264 in patients with recurrent or metastatic guanylyl cyclase C (GCC)-positive adenocarcinoma of the stomach or gastroesophageal junction.

Description:

The drug being tested in this study is called MLN0264. MLN0264 is being tested to treat tumors in people who have metastatic or recurrent gastric or gastroesophageal junction malignancies expressing guanylyl cyclase C (GCC). This study will assess tumor size reduction in patients who are administered MLN0264.

The study will enroll 42 to 81 patients. All participants will be administered MLN0264 at 1.8 mg/kg as a single, 30-minute, intravenous (IV) infusion on Day 1 of each 3-week treatment cycle, followed by a rest period of 20 days. Participants will continue to receive MLN0264 for up to 1 year or until disease progression or unacceptable toxicity occurs.

This multi-centre trial will be conducted worldwide. The overall time to participate in this study is approximately 19 months. Participants will make 3 to 6 visits to the clinic per treatment cycle, an end-of-treatment visit 30 days after the last dose of study medication, and follow-up assessments every 12 weeks until death or 6 months after the last patient completes treatment - whichever occurs first.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 81
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female participants 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 immunohistochemistry (IHC) evidence of guanylyl cyclase C (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 Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. All scans and x-rays used to document measurable disease must be done within 28 days before enrollment (ascites and bone lesions are not considered measureable disease).

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before enrollment.

6. Female participants 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 of contraception, 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 participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)

Male participants, 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 participant. (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 participant 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 x 10^9/L

• Platelet count = 100 x 10^9/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 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

10. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

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 participants 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. Participants with electrocardiogram (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 peripheral neuropathy (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 (testing is not mandatory).

14. Symptomatic brain metastases.

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Stomach
• Gastroesophageal Junction Expressing Guanylyl Cyclase C

Intervention

Drug:
• MLN0264
MLN0264 IV infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST)	ORR is defined as the percentage of participants with a complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.	From 21 days, every other cycle, starting with Cycle 2 until disease progression, death or study closure (up to 6 months after the enrollment of the last patient)	No
Secondary	Number of Participants With Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.; Serious adverse event (SAE) means any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.	From the first dose through 30 days after the last dose of study medication (Up to 13 months)	Yes
Secondary	Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings	Participants with at least one post-baseline potentially clinically significant serum chemistry, hematology, coagulation or urinalysis result.	Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 13 months)]	Yes
Secondary	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Participants with at least one potentially clinically significant post-baseline vital sign finding including measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.	Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 13 months)	Yes
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the date of first study drug administration to the date of first documentation of disease progression or death.	Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (approximately 18 months)	No
Secondary	Duration of Response	Duration of response is defined as the time from the date of first documentation of a confirmed response to the date of first documentation of disease progression.	From first documented response until disease progression (Up to 18 months)	No
Secondary	Disease Control Rate	Disease control rate is defined as the percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) with a minimum of 12 weeks' duration. Duration of SD is defined as the time from the date of first study drug administration to the date of first documentation of disease progression for patients who achieved SD as the best overall response.	Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Approximately 18 months)	No
Secondary	Overall Survival (OS)	Overall survival is defined as the time from the date of first study drug administration to the date of death.	: Until death or 6 months after the last patient completes treatment—whichever occurs first	No
Secondary	Cmax: Maximum Observed Serum Concentration for MLN0264	Maximum observed serum concentration (Cmax) is the peak serum concentration of a drug after administration, obtained directly from the serum concentration-time curve.	Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.	No
Secondary	Serum Concentration Conjugated and Unconjugated Total Antibody	Blood samples will be collected and sent to a laboratory to be tested for conjugated and unconjugated antibodies.	Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.	No
Secondary	Serum Concentration of Monomethyl Auristatin E (MMAE)	Blood samples will be collected and sent to a laboratory to be tested for MMAE.	Cycles 1-3 predose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days postdose. Cycles 4+ predose, 10 minutes, 4 hours, and 4 and 8 days postdose.	No
Secondary	Change from Baseline in Tumor Size	The best percentage of tumor reduction from baseline in the sum of the diameter will be calculated.	Day 21 of each 21-day cycle, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Approximately 18 months)	No
Secondary	Guanylyl Cyclase C (GCC) H-score Assessed by Immunohistochemistry (IHC)	GCC H-score is based on the sum of the 0 to 300 H-score for cytoplasmic staining and the 0 to 300 H-score for apical staining for a total possible H-score 0 to 600. Separate consent is required to obtain archival tumor specimens for GCC expression assessment prior to screening.	From pre-screening through end of study (approximately 20 months)	No
Secondary	Assessment of Antitherapeutic Antibodies (ATA)	Blood samples will be collected to assess the immunogenicity of MLN026 (ATA development) using a laboratory test. Neutralizing ATA assessment will be performed for ATA-positive samples only.	Pre-dose of each 21 day cycle and 30 days after last dose of study medication (Up to 13 months)	No