Pazopanib and Paclitaxel as First-Line Treatment for Subjects With Unresectable Stage III and Stage IV Melanoma

NCT01107665 | Completed Phase 2 Results DMC

• 4 other identifiers: UCI 09-532010-7443PZP113567NCI-2010-00748
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II single-arm, open-label, clinical trial evaluating the efficacy and safety of pazopanib in combination with paclitaxel as first line therapy for subjects with unresectable Stage III and Stage IV melanoma. Previous cytokine therapy is permitted. Subjects must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST). Subjects who are not candidates for curative intent treatments are eligible for this study.

Conditions

Stage III Melanoma; Stage IV Melanoma; Unresectable Melanoma

Keywords

pazopanib; paclitaxel; melanoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression-free Survival at 6 Months

  This is defined as the percentage of subjects who are free of RECIST-defined objective disease progression at 6 months after study treatment start. Subjects in the Intent-to-Treat (ITT) population who discontinue the study prior to 6 months will be included in the denominator when calculating the percentage. Progression is defined using the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  6 Months

Secondary Outcomes (6)

• Percentage of Participants Alive at 1 Year

  At 1 year after enrollment

• Percentage of Participants Alive at 2 Years

  At 2 years after enrollment

• Objective Response Rate (ORR)

  Up to 2 years

• Clinical Benefit Response (CBR)

  Up to 2 years

• Duration of Response (DR)

  Time from first documented evidence of response (CR/PR) until the first documented sign of disease progression or death, assessed up to 2 years

Other Outcomes (4)

• Concentrations of Plasma Proteins (Serum VEGF, Soluble VEGF Receptor 2, Serum Hypoxia-inducible Factor (HIF) and Serum TSP1) That May be Associated to Angiogenesis and Tumor Proliferation

  Day 1

• Tissue Levels of Angiogenic Markers Including Protein (p)53, HIF, Cluster of Differentiation (CD)31, Neuronal Nitric Oxide Synthase (nNOS), TSP1, and VEGF

  Day 1

• In Vitro Response of Tumor Cells Grown in Culture With Vascular Endothelial Cells to Pazopanib, Paclitaxel, Topotecan and Resveratrol

  Day 1

Study Arms (1)

Pazopanib and Paclitaxel

EXPERIMENTAL

Treatment on study will be administered in 4-week cycles. Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.

Drug: Pazopanib and Paclitaxel

Interventions

Pazopanib and Paclitaxel DRUG

Paclitaxel will be administered intravenously at a starting dose of 80mg/m2 weekly for 3 weeks followed by a 1-week rest. Pazopanib will be administered orally, in a continuous regimen, with a starting dose of 800mg daily.

Also known as: Pazopanib monohydrochloride salt and Taxol

Pazopanib and Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up. Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol. Note: It is not necessary that informed consent be obtained within the protocol-specified screening window.
• Histologically confirmed cutaneous melanoma with 1) unresectable Stage III disease, or 2) Stage IV disease by American Joint Committee on Cancer (AJCC) criteria.
• Must have measurable disease \[i.e. with at least one measurable lesion, per RECIST\]. A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥20mm using conventional techniques or ≥10mm with spiral CT scan.
• Note: Subjects should be excluded if all baseline measurable lesions are within previously irradiated areas. Subjects participating in the exploratory analysis shall not have the biopsied lesion(s) as the only sites of measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Age 18 years old or older
• A female is eligible to enter and participate in this study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:
• A hysterectomy
• A bilateral oophorectomy (ovariectomy)
• A bilateral tubal ligation
• Is post-menopausal
• Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value \>40 milliinternational unit (mIU)/mL and an estradiol value \<40pg/mL (\<140 pmol/L).
• Subjects must discontinue HRT prior to study enrollment due to the potential for inhibition of Cytochrome P450 (CYP) enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female subject is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.
• Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• Prior treatment with cytotoxic anti-cancer therapy. (Previous cytokine or investigational immunotherapy are permitted, but must be completed 28 days prior to first dose of study medication).
• Prior use of other investigational or licensed tyrosine kinase inhibitors (TKIs), or agents which target vascular endothelial growth factor (VEGF) or VEGF receptors (ie. bevacizumab, VEGF-Trap).
• Known history of dose-limiting hypersensitivity reactions to paclitaxel/Cremophor EL.
• Pregnant or lactating female. Female subjects who are lactating are eligible if they discontinue nursing prior to the first dose of study drug and refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
• Melanoma of ocular origin.
• History of another malignancy. Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• Life expectancy less than 3 months.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis except for subjects who have previously-treated CNS metastases (surgery with or without radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria:
• Are asymptomatic
• Have had no evidence of active CNS metastases for more or equal 6 months prior to enrollment
• Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
• Clinically significant gastrointestinal abnormalities including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel that could affect the absorption of study drug

Sponsors & Collaborators

• University of California, Irvine: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Related Publications (1)

• Fruehauf JP, El-Masry M, Osann K, Parmakhtiar B, Yamamoto M, Jakowatz JG. Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2018 Aug;82(2):353-360. doi: 10.1007/s00280-018-3624-6. Epub 2018 Jun 25.

  PMID: 29943192 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

pazopanib; Paclitaxel

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Analysis on one secondary outcome and other exploratory outcomes were not performed due to depleted funding.

Results Point of Contact

• Title: UC Irvine Health / Chao Family Comprehensive Cancer Center
• Organization: UC Irvine Health / Chao Family Comprehensive Cancer Center

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• John Fruehauf, MD, PhD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: April 21, 2010
• Study Start: August 1, 2010
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: August 7, 2019
• Results First Posted: February 1, 2019

Record last verified: 2019-07

Locations

US (1)