Ipilimumab With Carboplatin and Paclitaxel in Patients With Unresectable Stage III and Stage IV Melanoma

A Phase II Study of Ipilimumab in Combination With Carboplatin and Paclitaxel in Patients With Unresectable Stage III or Stage IV Melanoma

The safety of the combination of ipilimumab with carboplatin/paclitaxel treatment with two different dosing schedules will be investigated in patients with metastatic melanoma. This protocol will also investigate both the clinical benefit of this combination and the features of the host immune system that may predict response to ipilimumab with chemotherapy in patients with unresectable Stage III and Stage IV melanoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Untreated Stage III Melanoma or Stage IV Melanoma
• Intervention / Treatment: Biological: Ipilimumab; Drug: Carboplatin; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to give written informed consent.
• Histologic diagnosis of malignant melanoma
• Untreated unresectable Stage III melanoma with N3 macroscopic lymph nodes or in-transit/satellite metastases or Stage IV melanoma (note that prior adjuvant melanoma therapy is permitted). Prior treatment with BRAF inhibitors in the metastatic setting is also permitted.
• Measurable/evaluable disease

• Required values for initial laboratory tests:

  • WBC ≥ 2000/uL
  • ANC ≥ 1.5 x 10E9/L
  • Platelets ≥ 100 x 10E9/L
  • Hemoglobin ≥ 90 g/L (may be transfused)
  • Creatinine Clearance ≥ 50 ml/min (calculated -Cockcroft-Gault)

  • AST/ALT ≤ 2.5 x ULN for patients without liver metastasis,

    ≤ 5 times for liver metastases

  • Bilirubin ≤ 2.5 x ULN
• No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
• ECOG Performance status of 0 or 1.
• Men and women, ≥ 18 years of age. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:

• Amenorrhea ≥ 12 consecutive months without another cause, or
• For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 U/L. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.

Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last doseof investigational product] in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

• Evidence of symptomatic CNS lesions as determined by the investigator (patients with asymptomatic lesions or previously irradiated or surgically resected are eligible).
• Any other malignancy from which the patient has been disease-free for less than one year, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
• Patients with ≥ Grade 2 peripheral neuropathy.
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
• A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
• Concomitant therapy with any of the following: IL 2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids.

• Women of childbearing potential (WOCBP), defined above, who:

  1. are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
  2. have a positive pregnancy test at baseline, or
  3. are pregnant or breastfeeding.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Arm A: Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 4, week 7, week 10, and week 13)	Biological: Ipilimumab; 3 mg/kg; Other Names: YERVOY; Drug: Carboplatin; AUC = 6; Drug: Paclitaxel; 175 mg/m2
Experimental: B; Carboplatin (week 1, week 4, week 7, week 10, and week 13) Paclitaxel (week 1, week 4, week 7, week 10, and week 13) Ipilimumab (week 5, week 8, week 11, and week 14)	Biological: Ipilimumab; 3 mg/kg; Other Names: YERVOY; Drug: Carboplatin; AUC = 6; Drug: Paclitaxel; 175 mg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Putative Early Cellular and/or Molecular Biomarker levels	27 months
To determine ORR and clinical benefit rate (ORR + SD ≥ 24 weeks), by immune related response criteria (irRC) and modified WHO criteria (mWHO) of ipilimumab when given with carboplatin and paclitaxel at two different dosing regimens.	48 months
To determine the overall survival (OS) of patients receiving ipilimumab with carboplatin and paclitaxel.	48 months
To determine progression free survival (PFS) per irRC and mWHO of patients receiving ipilimumab with carboplatin and paclitaxel.	48 months

Collaborators and Investigators

• Sponsor: Jewish General Hospital
• Investigators: Principal Investigator: Wilson Miller, MD, PhD, Jewish General Hospital; Principal Investigator: Rahima Jamal, MD, Notre-Dame Hospital (CHUM)

Publications and helpful links

General Publications

• Jamal R, Lapointe R, Cocolakis E, Thebault P, Kazemi S, Friedmann JE, Dionne J, Cailhier JF, Belanger K, Ayoub JP, Le H, Lambert C, El-Hajjar J, van Kempen LC, Spatz A, Miller WH Jr. Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma. J Immunother Cancer. 2017 Nov 21;5(1):83. doi: 10.1186/s40425-017-0290-x.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): February 1, 2017
• Study Completion (Anticipated): May 1, 2026

Study Registration Dates

• First Submitted: August 29, 2012
• First Submitted That Met QC Criteria: August 29, 2012
• First Posted (Estimate): August 31, 2012

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Paclitaxel; Ipilimumab
• Other Study ID Numbers: CA184-195