Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies

Metastatic Melanoma Clinical Trial

Official title: Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies

Status Active, not recruiting

Clinical Trial Summary

This phase Ib trial studies the side effects and best dose of selinexor when given together with several different standard chemotherapy or immunotherapy regimens in treating patients with malignancies that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Selinexor may stop the growth of cancer cells by blocking enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Studying selinexor with different standard chemotherapy or immunotherapy regimens may help doctors learn the side effects and best dose of selinexor that can be given with different types of treatments in one study.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To establish the safety and tolerability of selinexor when given in combination with standard chemotherapy or immunotherapy regimens.

SECONDARY OBJECTIVE:

I. To determine disease control rate, objective tumor response rate, and progression free survival of selinexor administered with standard chemotherapy or immunotherapy treatments.

EXPLORATORY OBJECTIVES:

I. To determine the correlation of translational biomarkers. II. To compare serial assessment of mutation status in biopsies obtained at baseline and progression after clinical response to combination therapy.

III. To assess the efficacy of olanzapine as incorporated in the National Comprehensive Cancer Network (NCCN) guidelines for the management of chemotherapy-induced nausea and cachexia.

OUTLINE: This is a dose-escalation study of selinexor. Patients are assigned to 1 of 15 treatment arms.

ARM A: Patients receive selinexor orally (PO) on days 1, 8, and 15 and carboplatin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM B: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) on days 1-14. Patients then receive selinexor PO on days 1, 3, 8 and 10 and paclitaxel IV over 3 hours on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After 8 cycles, of combination treatment, patients can continue single agent selinexor until disease progression.

ARM C: Patients receive selinexor PO on days 1, 8, and 15 and eribulin IV over 1 hour on days 1 and 8. Combination treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression.

ARM D: Patients receive selinexor PO on days 1, 8, and 15, doxorubicin IV over 90 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM E: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for up to 8 cycles depending on cancer type (6 cycles for non-small cell lung cancer, up to 8 cycles for ovarian cancer and other histological malignancies) in the absence of disease progression or unacceptable toxicity. After 6 to 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM F: Patients receive selinexor PO on days 1, 8, and 15 and carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM G: Patients receive selinexor PO on days 1, 8, and 15 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM H: Patients receive selinexor PO on days 1, 8, 15 and 22, irinotecan hydrochloride IV over 90 minutes, fluorouracil continuous IV and leucovorin calcium IV over 2 hours on days 1 and 15. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM I: Patients receive selinexor PO on days 1, 8 and 15 and irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM J: Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression. (ARM CLOSED)

ARM K: Patients receive selinexor PO on days 1, 8, 15, and 22 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (ARM CLOSED)

ARM L: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM M: Patients receive selinexor PO twice weekly (e.g. Monday/Wednesday or Tuesday/Thursday or Wednesday/Friday or Thursday/Saturday or Friday/Sunday) and nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARMS N AND O: Patients receive selinexor PO on days 1, 8, and 15, nivolumab IV over 30 minutes on day 1, and ipilimumab PO QD on day 1. Cycles repeat every 3 weeks for 4 cycles. Starting cycle 5, patients receive selinexor PO on days 1, 8, 15, and 22 and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM P: Patients receive selinexor PO on days 1, 8, 15, 22, 29, and 36, nivolumab IV over 30 minutes on days 1, 15, and 29, and ipilimumab PO QD on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients may continue to receive selinexor and chemotherapy after confirmed progressive disease in the absence of clinical deterioration and if the investigator considers that the patient continues to receive benefit from the treatment.

After completion of study treatment, patients are followed up every 12 weeks for 1 year. ;

Related Conditions & MeSH terms

• Advanced Malignant Solid Neoplasm
• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Clinical Stage III Cutaneous Melanoma AJCC v8
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Fallopian Tube Carcinoma
• Lung Neoplasms
• Melanoma
• Metastatic Lung Non-Small Cell Carcinoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Melanoma
• Metastatic Renal Cell Carcinoma
• Neoplasms
• Ovarian Carcinoma
• Pathologic Stage III Cutaneous Melanoma AJCC v8
• Pathologic Stage IIIA Cutaneous Melanoma AJCC v8
• Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IIID Cutaneous Melanoma AJCC v8
• Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Primary Peritoneal Carcinoma
• Skin Neoplasms
• Stage III Lung Cancer AJCC v8
• Stage III Renal Cell Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8
• Stage IIIB Lung Cancer AJCC v8
• Stage IIIC Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8
• Triple-Negative Breast Carcinoma
• Unresectable Lung Non-Small Cell Carcinoma
• Unresectable Melanoma
• Unresectable Renal Cell Carcinoma

• NCT number: NCT02419495
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 26, 2015
• Completion date: December 31, 2024