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MelanomaPhase 2NCT01740401

CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

A Phase 2 study testing Cyclophosphamide in people with Melanoma, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to see whether the combination of low-dose Cyclophosphamide and Anti-CTLA4 (Ipilimumab) will stop tumor growth in patients with advanced skin cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Oct 2012to Dec 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men \& women, ages ≥18
  • Willing/able to give written informed consent.
  • Histologic diagnosis of unresectable AJCC Stage III/IV malignant melanoma
  • At least 2wks must have elapsed since last chemotherapy, immunotherapy, hormonal therapy, radiotherapy or major surgery \& beginning of protocol therapy. At least 6wks for nitrosoureas, mitomycin C, \& liposomal doxorubicin
  • Toxicity related to prior therapy must either have returned to ≤ grade 1 or baseline.
  • Two punch tumor biopsy at Screening and Wk12 (4mm diameter) must be provided for immune analysis/staining if patients have accessible disease. Biopsies are optional during the Maintenance Period.Site of tumor biopsy s/n be only site of measurable disease. Minimum of 5 out of 1st 10 patients in stage I of the protocol must have biopsy accessible disease.
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  • Patients must have measurable disease defined as @ least 1 lesion that can be accurately measured in @ least 1 dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
  • Required values for initial laboratory tests:
  • WBC ≥ 2000/uL
  • ANC ≥ 1000/uL
  • Platelets ≥ 50 x 103/uL
  • Hemoglobin ≥ 9.5 g/dL
  • Creatinine ≤ 3.0 x ULN
  • AST/ALT ≤ 2.5 x ULN for patients without liver metastasis, ≤ 5 x ULN for patients with liver metastasis
  • Bilirubin ≤ 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • Life expectancy of at least 4mos
  • Patients w/stable, treated central nervous system (CNS) metastasis are eligible
  • ECOG Performance Status Score 0-1
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout study \& for up to 26wks 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 w/o another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), documented serum follicle-stimulating hormone (FSH) level ≥ 35 mIU/mL.
  • Women who are using oral contraceptives, other hormonal contraceptives (vaginal products/skin patches/implanted/injectable products), mechanical products such as an intrauterine device or barrier methods (diaphragm/condoms/ spermicides) to prevent pregnancy,are practicing abstinence or where their partner is sterile (eg vasectomy) should be considered to be of childbearing potential.
  • WOCBP must have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) w/in 72hrs before the start of ipilimumab.
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and up to 26wks after last dose of investigational product] in a way that risk of pregnancy is minimized.

Who cannot join

  • Any other malignancy from which patient has been disease-free for less than 5yrs, with the exception of adequately treated \& cured 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 (eg Guillain-Barre Syndrome and Myasthenia Gravis).
  • Any underlying medical or psychiatric condition, which in the opinion of investigator will make administration of ipilimumab hazardous or obscure interpretation of AEs, like a condition associated with frequent diarrhea.
  • Uncontrolled or significant cardiovascular disease
  • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1mo before/after any dose of ipilimumab).
  • History of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
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  • Concomitant therapy with any of following: IL 2, interferon, other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (>60mg prednisone/day).
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg infectious) illness.
  • Women of childbearing potential (WOCBP), defined above who:
  • are unwilling/unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26wks after cessation of study drug, or
  • have a positive pregnancy test at baseline, or
  • are pregnant or breastfeeding.
  • Persons of reproductive potential who are unwilling to use an adequate method of contraception throughout treatment \& for at least 26wks after ipilimumab is stopped.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • New York University Langone Clinical Cancer Center

    New York, New York, 10016

Other trials in United States

About this study

Official title: Phase II Study of CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

The purpose of this study is to see whether the combination of low-dose Cyclophosphamide and Anti-CTLA4 (Ipilimumab) will stop tumor growth in patients with advanced skin cancer. The investigators expect to see an increase in response rate of the combination over Anti-CTLA-4 alone and estimate a response rate of approximately 20 % in the proposed population.

Read the detailed description

The transient removal of CTLA-4-mediated inhibition (CTLA-4 blockade) can induce effective anti-tumor immunity. Efficacy of CTLA-4 blockade as a single agent has been shown in melanoma 53. It has been hypothesized that anti-CTLA-4 antibody might deplete Treg cells 54, inducing autoimmunity. However, patients receiving Ipilimumab have not shown a decrease in Treg number or function in peripheral blood 55.

This trial will answer the question if the combination of Anti-CTLA 4 (following a well established regimen of Ipilimumab) and Cyclophosphamide (given at immunomodulatory doses) will result in antitumor activity in patients with metastatic melanoma due to synergistic immunomodulating effects by overcoming tolerance.

Conditions
Melanoma
Being tested
Cyclophosphamide
Keywords
Melanoma, Advanced Malignant Melanoma, Anti CTLA4 Blockade, Progression Free Survival, Interventional Therapy, Phase II Clinical Trial, Immunotherapy, T Cell Activation
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Ipilimumab (BMS-734016, MDX010, MDX-CTLA4), Cytoxin

    This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Study groups in NCT01740401
Study groupRoleWhat they receive
Cyclophosphamide, IpilimumabExperimentalTreatment: Cyclophosphamide 300 mg/m2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn) Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv
Receives: Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR)

    Objective response rate (ORR) using mWHO RC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: 12 weeks

Secondary outcomes (2)

  1. Progression-free Survival

    Progression-free survival is measured from date of entry to date of 1st documented evidence of recurrence, confirmation of PD, or death (whichever is 1st). T regulatory cells are measured on D1 (pre CTX) \& D3 of each cycle.

    Measured: Week 60

  2. T Regulatory Cell Profile in Peripheral Blood

    Peripheral blood taken at baseline/various therapeutic time points/possibly maintenance cycles to evaluate T regulatory cells identified, serially monitored by polychromatic flow cytometry using FoxP3+/CD4+/CD127low/CD25hi markers.

    Measured: Week 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionDec 2013
  4. Study completionDec 2014

Why it stopped: Primary Endpoint not met

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01740401
Sponsor's protocol ID
GCO 14-0677
Other IDs
114660
Status last verified
Oct 2017
First submitted
29 Nov 2012
Last updated
6 Dec 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide in people with Melanoma, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01740401.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2017.

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