Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

NCT02159989 | Completed Phase 1 Results FDA Drug

• 6 other identifiers: NCI-2014-011072013-06659585P30CA016672U01CA062461UM1CA186688
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of sapanisertib and ziv-aflibercept in treating patients with solid tumors that have come back (recurrent) and have spread to another place in the body (metastatic) or cannot be removed by surgery (unresectable). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ziv-aflibercept may stop the growth of solid tumors by blocking the growth of new blood vessels necessary for tumor growth. Giving sapanisertib with ziv-aflibercept may kill more tumor cells.

Conditions

Advanced Malignant Solid Neoplasm; Fibrolamellar Carcinoma; Metastatic Malignant Solid Neoplasm; Ovarian Carcinoma; Pancreatic Neuroendocrine Tumor; Recurrent Malignant Solid Neoplasm; Refractory Malignant Solid Neoplasm; Unresectable Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD)

  DLTs were defined as adverse events per Common Terminology Criteria for Adverse Events version 4.0, related to study agents and fulfilling one of the following criteria: Hematologic * Grade 4 neutropenia for \> 7 days * Febrile neutropenia (defined as absolute neutrophil count \[ANC\] \< 1.0 x 109/L and fever ≥ 38.5° C) or grade ≥3 infection with ANC≤1.0 x 109/L. * Platelet count \< 25,000/mm for \> 7 days Non-hematologic * Any toxicity ≥grade 3 that persists for \> 7 days, except: 1. nausea/vomiting, diarrhea and electrolyte imbalances; 2. grade 3 lab abnormalities that are asymptomatic and responsive to supportive measures and that are without clinical consequence; and 3. grade 3 hyperglycemia or grade 3 diabetes that can be stably controlled. * Delay of treatment \> 7 days due to hematologic and \> 14 days due to non-hematologic toxicity MTD is the highest dose level at which no more than 1 of 6 evaluable patients had a DLT

  DLT was assessed during Cycle 1 (28-day cycle).

Secondary Outcomes (2)

• Tumor Response by Change in Tumor Size From Baseline: Objective Response Rate Per RECIST v1.1

  At baseline and every 8 weeks. Confirmatory scans done 8 (not less than 4) weeks following initial documentation of objective response. If a patient has been on the study for 12 months, the response was evaluated every 12 weeks, assessed up to 3 years.

• Tumor Response by Change in Tumor Size From Baseline: Disease Control Rate Per RECIST v1.1

  At baseline and every 8 weeks. Confirmatory scans done 8 (not less than 4) weeks following initial documentation of objective response. If a patient has been on the study for 12 months, the response was evaluated every 12 weeks, assessed up to 3 years.

Study Arms (1)

Treatment (sapanisertib, ziv-aflibercept)

EXPERIMENTAL

Patients receive sapanisertib PO QD on days 2-4, 9-11, 16-18, and 23-25 and ziv-aflibercept IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Sapanisertib; Biological: Ziv-Aflibercept

Interventions

Sapanisertib DRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

Treatment (sapanisertib, ziv-aflibercept)

Ziv-Aflibercept BIOLOGICAL

Given IV

Also known as: Aflibercept, AVE0005, Eylea, Vascular Endothelial Growth Factor Trap, VEGF Trap, VEGF Trap R1R2, VEGF-Trap, Zaltrap

Treatment (sapanisertib, ziv-aflibercept)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced or metastatic cancer that is refractory to standard therapy or relapsed after standard therapy; patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Patients enrolled in the expansion cohort must have biopsiable disease; there will be preferential enrollment of patients with pancreatic neuroendocrine tumors or ovarian cancer during the dose expansion cohort
• Patients must be \>= 4 weeks beyond treatment of any chemotherapy, other investigational therapy, hormonal, biological, targeted agents or radiotherapy, and must have recovered to =\< grade 1 toxicity or previous baseline for each toxicity; exception: patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Life expectancy of greater than 3 months
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine =\< 1.5 x institutional upper limit of normal OR creatinine clearance \>= 60 mL/min for patients with creatinine levels above institutional normal
• Fasting serum glucose =\< 130 mg/dL
• Fasting triglycerides =\< 300 mg/dL
• Glycosylated hemoglobin (HbA1c) \< 7.0%

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to =\< grade 1 adverse events due to agents administered more than 4 weeks earlier
• Patients who are receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN0128 (TAK-228) or ziv-aflibercept
• Uncontrolled intercurrent illness including active infection
• Pregnant women are excluded from this study because MLN0128 (TAK-228) and ziv-aflibercept are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MLN0128 (TAK-228) and ziv-aflibercept, breastfeeding should be discontinued if the mother is treated with MLN0128 (TAK-228) and ziv-aflibercept; these potential risks may also apply to other agents used in this study
• Patients with known human immunodeficiency virus infection are not to be enrolled in the study
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days or manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease that may alter the absorption of MLN0128 (TAK-228)
• New York Heart Association class III or greater congestive heart failure within last 6 months or uncontrolled hyperlipidemia (cholesterol \> 300 mg/dl; triglyceride 2.5 X upper limit of normal \[ULN\] despite lipid lowering agent) within last 3 months
• History of uncontrolled hypertension, defined as blood pressure \> 150/95 mmHg, or systolic blood pressure \> 180 mmHg when diastolic blood pressure \< 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment
• Urine protein should be screened by dipstick or urine analysis; for proteinuria \> 1+ or urine protein: creatinine ratio \> 1.0, 24-hour urine protein should be obtained and the level should be \< 2000 mg for patient enrollment
• Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of- therapeutic range international normalized ratio (INR) (\> 3) within the 4 weeks prior to drug administration
• Evidence of clinically significant bleeding diathesis or underlying coagulopathy, non-healing wound
• History of any of the following within the last 6 months prior to study entry:
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Fibrolamellar hepatocellular carcinoma; Neoplasm Metastasis; Ovarian Neoplasms; Adenoma, Islet Cell

Interventions

sapanisertib; aflibercept

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pancreatic Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

Results Point of Contact

• Title: Aung Naing
• Organization: MD Anderson Cancer Center

anaing@mdanderson.org

713-563-3885

Study Officials

• Aung Naing

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2014
• First Posted: June 10, 2014
• Study Start: June 18, 2014
• Primary Completion: June 29, 2021
• Study Completion: January 29, 2024
• Last Updated: October 20, 2025
• Results First Posted: October 20, 2025

Record last verified: 2025-09

Locations

US (1)