Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery

NCT01465659 | Completed Phase 1 Results DMC

• 3 other identifiers: NU 11I03NCI-2011-02939STU00053541
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I/II trial studies the side effects and best dose of temozolomide and pazopanib hydrochloride when given together and to see how well they work in treating patients with advanced pancreatic neuroendocrine tumors (PNET) that cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth. Giving temozolomide together with pazopanib hydrochloride may be an effective treatment for patients with PNET.

Conditions

Pancreatic Alpha Cell Carcinoma; Pancreatic Beta Islet Cell Carcinoma; Pancreatic Delta Cell Carcinoma; Pancreatic G-cell Carcinoma; Recurrent Islet Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Determine the Maximum Tolerated Dose (MTD) of Temozolomide in Combination With 400 mg Pazopanib in Patients With Advanced Pancreatic Neuroendocrine Tumor (PNET) in Phase I

  MTD and recommended phase II dose (RP2D) determination for the combination of temozolomide in combination with 400mg pazopanib in patients with advanced PNET will be achieved using a standard "3+3" dose escalation/de-escalation design. After each 3 patients are enrolled into the study, further enrollment will be temporarily suspended until safety has been reviewed for the first 28 days of treatment to determine if dose limiting toxicities have been experienced by patients and if a further 3 patients should be enrolled at the current dose or dose escalation/de-escalation for the next 3 patients should occur.

  After 28 days (1 cycle of treatment)

• Overall Response Rate (ORR) in Patients With Advanced Neuroendocrine Tumors (PNET) Treated With Temozolomide and Pazopanib Combination Treatment at the RP2D in Phase II

  Overall response rate will be determined by the number of patients who's best response as assessed by RECIST 1.1 is complete response (CR) and partial response (PR) in patients with PNET that are enrolled at the recommended phase II dose (RP2D) (PK cohort included). CR= Disappearance of all target lesions PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  After two cycles of treatment (8 weeks)

Secondary Outcomes (6)

• Number of Patients Who Experience Toxicity Events Undergoing This Treatment.

  During treatment and up to one month post last dose of study drug. Range of cycles completed by patients was 1-41 where one cycle =28 days.

• Plasma Temozolomide Concentration in the Blood at Various Timepoints After Administration

  Multiple timepoints during Days 1-3 of cycle 1 and cycle 2 (1 cycle =28 days)

• Progression Free Survival (PFS)

  Baseline and after every 2 cycles of treatment (8 weeks) for up to 40 months

• Overall Survival (OS)

  Baseline and after every 2 cycles of treatment (8 weeks) and up to 60 months

• Number of Patients Experiencing Response to Treatment or Stable Disease (Disease Control Rate)

  After every 2 courses of treatment (8 weeks) for up to 41 cycles where 1 cycle =28 days.

Other Outcomes (2)

• Determine the Relationship Between Tumor Blood Flow and Overall Response Rate

  At Baseline and after two corurses of treatment (8 weeks)

• Amount of a Particular Tumor Biomarker in Blood as Correlated With Progression Free Survival

  Baseline and at Response assessment after two courses of treatment (8 weeks)

Study Arms (3)

Temozolomide 100 mg/m2 and Pazopanib 400 mg

EXPERIMENTAL

Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

Drug: temozolomide; Drug: pazopanib hydrochloride

Temozolomide 75 mg/m2 and Pazopanib 400 mg

EXPERIMENTAL

Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

Drug: temozolomide; Drug: pazopanib hydrochloride

Temozolomide 150 mg/m2 and Pazopanib 400 mg

EXPERIMENTAL

Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28

Drug: temozolomide; Drug: pazopanib hydrochloride

Interventions

temozolomide DRUG

Given PO

Also known as: SCH 52365, Temodal, Temodar, TMZ

Temozolomide 100 mg/m2 and Pazopanib 400 mg; Temozolomide 150 mg/m2 and Pazopanib 400 mg; Temozolomide 75 mg/m2 and Pazopanib 400 mg

pazopanib hydrochloride DRUG

Given PO

Also known as: GW786034, Votrient

Temozolomide 100 mg/m2 and Pazopanib 400 mg; Temozolomide 150 mg/m2 and Pazopanib 400 mg; Temozolomide 75 mg/m2 and Pazopanib 400 mg

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed islet cell carcinoma (PNET) not amenable to surgical resection
• Patients may have had 0-2 prior therapies; prior chemoembolization or local ablative therapies are permitted if completed \>= 6 weeks prior to study enrollment
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Patients must have a life expectancy \> 3 months
• Patients must have radiographically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
• Patients' baseline blood pressure must be adequately controlled with or without antihypertensive medications prior to enrollment (systolic \< 140 mmHg, diastolic \< 90 mmHg)
• Patients must have left ventricular ejection fraction (LVEF) \>= 50 as measured by echocardiogram or multi gated acquisition scan (MUGA)
• Absolute neutrophil count (ANC) \>= 1,500/µL
• Platelets \>= 100,000/µL
• Hemoglobin \>= 9.0 g/dL
• Total bilirubin =\< 2 mg/dL or =\< 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 5 times ULN
• International normalized ratio (INR) =\< 1.2 times upper limit of normal (ULN); subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
• Activated partial thromboplastin time (aPTT) =\< 1.2 x ULN
• Albumin \>= 2.8 g/dL

You may not qualify if:

• Patients taking immunosuppressive medications (including systemic corticosteroids unless used for adrenal replacement), appetite stimulants, acute therapy for asthma or acute bronchitis exacerbation, or antiemetics are NOT eligible for participation
• Patients with known human immunodeficiency virus (HIV) infection are NOT eligible for participation
• Patients with uncontrolled hypertension (\>= 140/90 mmHg) are NOT eligible for participation
• Patients with uncontrolled hyperlipidemia (total cholesterol \> 350 or triglycerides \> 300) are NOT eligible for participation
• Patients who have had a transfusion within 7 days of screening are NOT eligible for participation
• Patients with symptomatic brain or bone metastasis (mets) are NOT eligible for participation; prior radiation and/or steroid therapy for brain or bone mets must be completed \>= 2 weeks prior to study enrollment
• Patients with a history of seizure disorder requiring antiepileptic medication or brain metastases with seizures are NOT eligible for participation
• Patients with an active second malignancy (other than non-melanoma skin cancer or cervical carcinoma in situ) are NOT eligible for participation; patients who have a history of malignancy are not considered to have a currently active malignancy if they have completed therapy and are now considered by their physician to be at \< 30% risk for relapse
• Patients with clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding are NOT eligible for participation; these may include (but are not limited to):
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease)
• Other gastrointestinal conditions with increased risk of perforation
• Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment are NOT eligible for participation
• Patients with clinically significant gastrointestinal abnormalities that may affect absorption of the investigational product including are NOT eligible for participation; these may include (but are not limited to):

Sponsors & Collaborators

• Northwestern University: lead
• Robert H. Lurie Cancer Center: collaborator
• National Comprehensive Cancer Network: collaborator
• GlaxoSmithKline: collaborator

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Washington Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Islet Cell

Interventions

Temozolomide; pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

On review of the phase II data it was determined that the study did not meet continuation criteria according to Simon II stage design and would not meet criteria even with the remaining slot filled. The study was closed to further accrual.

Results Point of Contact

• Title: Sheetal Kircher, MD
• Organization: Northwestern University

sheetal.kircher@nm.org

312-695-0990

Study Officials

• Halla Nimeiri

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 4, 2011
• First Posted: November 7, 2011
• Study Start: December 12, 2011
• Primary Completion: July 30, 2018
• Study Completion: January 27, 2021
• Last Updated: August 5, 2021
• Results First Posted: June 17, 2020

Record last verified: 2021-07

Locations

US (5)