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A PHASEII STUDY EVALUATING INTRAVENOUS MELPHALAN WITH AUTOLOGOUS WHOLE BLOOD STEM CELL TRANSPLANTATION (PBSCT)OVER THREE CYCLES IN PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER (MEL-CAP). (MEL-CAP)

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ClinicalTrials.gov Identifier: NCT01907009
Recruitment Status : Unknown
Verified July 2013 by Barts & The London NHS Trust.
Recruitment status was:  Recruiting
First Posted : July 24, 2013
Last Update Posted : September 9, 2015
Sponsor:
Information provided by (Responsible Party):
Barts & The London NHS Trust

Brief Summary:

The management of (castration-resistant) prostate cancer (CRPC) is becoming increasingly complex. The use of peripheral anti-androgens with gonadorelin analogues (maximum androgen blockade) is common place. Following the failure of such an approach, several strategies may be employed. Both corticosteroids and estrogens have a role and increasingly chemotherapy is being used. The demonstration of enhanced survival using 3 weekly docetaxel has meant that this is viewed by many as the standard of care for fit patients.

Melphalan is an established alkylating drug that has demonstrated some activity in CRPC, but to date, myelosuppression has prevented adequate dosing. We have recently conducted a phase I dose escalation study using melphalan and whole blood stem cell re-infusion and it shows that median overall survival is 22 months, which is higher than the median survival rate of 19 months for Docetaxel

Data from a previous phase I study has proved the successful administration of higher doses of IV Melphalan in combination with autologous blood infusion in patients with Castration-resistant prostate cancer.

Rapid falls in circulating tumour cells were seen within 2 weeks of starting Melphalan, however slow platelet recovery meant longer periods of platelet transfusion. For this study we intend to assess the efficacy of an intensified intravenous melphalan with autologous whole blood stem cell transplantation over three treatment cycles.

39 patients will be enrolled over a 3 year period and at least 17 patients need to survive progression free at least 6-months for this study to be considered positive.

Mel-CAP is a combination chemotherapy consisting of two chemotherapy drugs:

MELPHALAN and LENOGRASTIM for 3 cycles alternately.


Condition or disease Intervention/treatment Phase
Castrate Resistant Prostate Cancer Drug: Melphalan Drug: Lenograstim Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASEII STUDY EVALUATING INTRAVENOUS MELPHALAN WITH AUTOLOGOUS WHOLE BLOOD STEM CELL TRANSPLANTATION (PBSCT)OVER THREE CYCLES IN PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER (MEL-CAP).
Study Start Date : January 2013
Estimated Primary Completion Date : January 2016
Estimated Study Completion Date : September 2017


Arm Intervention/treatment
Experimental: Registration.

MELCAP study has only one arm. All suitable patients will receive 3 cycles of melphalan and lenograstim alternately.

Patient will start with a 3 day lenograstim (at 10mcg/kg/day) to boost up the blood cell count.

Upon reaching sufficient blood cell count, patients will undergo a venesection and roughly a pint of blood is taken. After this patients will receive first cycle of Melphalan (60mg/m2). The following day patient will receive back the previously given whole blood. A treament break of 6 days between the cycles is given. After the break the patient will be given Lenograstim (10mcg/kg/day)for 6 days (until sufficient).

The above regimen is repeated for cycle 2 and cycle 3 with only exception of Melphalan is given at 40mg/m2. After the cycle 3, Lenograstrim is given at 263 mcg/day for 10 days.

Upon treatment completion, patients will be followed for 2 years. If the patients show disease progression, they will start hormone therapy.

Drug: Melphalan
Patients will receive Melphalan in three cycles In the first cycle they recieve 60mg/m2 and then 40mg/m2 in the next two cycles.

Drug: Lenograstim

Starting Lenograstim will be at 10mcg/kg/day and between cycles at 10mcg/kgs/day.

After the third cycle patient will receive 263mcg/day for 10 days.





Primary Outcome Measures :
  1. To determine the efficacy of intensified intravenous Melphalan with autologous whole blood stem cell transplantation in patients with castration resistant prostate cancer using progression free survival. [ Time Frame: 6 months progression free survival ]

Secondary Outcome Measures :
  1. To determine weather early falls (two weeks)in circulating tumor cells (CTC)predict the progression free survival [ Time Frame: 2 weeks ]
  2. To assess the changes in prostate specific antigen pre and post treament [ Time Frame: 6 months ]
  3. To study progression free survival and overall survival [ Time Frame: 6 months. ]
  4. To assess the effect of this schedule in reintroduction of hormone senstivity [ Time Frame: 6 months ]
  5. To study the Quality of life. [ Time Frame: 6 months ]
    QLQ-30 and PR-25 questionnaires will be collected.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men aged ≥18 years
  2. Histological diagnosis of prostate cancer
  3. Progressive Castration-resistant Prostate Cancer defined as:

    • a rising PSA; or
    • development of new sites of disease in the presence of a suppressed testosterone (<1.5 nmol/l); or
    • if testosterone >1.5 nmol/l, maximum androgen blockade failure (MAB) (MAB = GnRH analogue and peripheral anti-androgen - flutamide 250 mg 3x/day or bicalutamide 50 mg/ day or cyproterone 100mg 3x/day)
  4. ECOG performance status 0-2
  5. Adequate haematological reserve:

    • Unsupported Hb >9.0 g/l
    • Platelets >100x109/l
    • WBC >3x109/l
    • Neutrophils >1.5x109/l
  6. Renal sufficiency:

    •Creatinine <200 µmol/l

  7. Hepatic sufficiency:

    • Bilirubin <30 µmol/l
    • ALT <3xULN unless due to liver metastasis
  8. Able to give written informed consent and comply with the protocol study procedures

Exclusion Criteria:

  1. Patients who have suffered a previous hypersensitivity reaction to melphalan
  2. Patients with known hypersensitivity to lenograstim or to any of the excipients
  3. History of myeloid malignancy
  4. Lenograstim should not be administered concurrently with cytotoxic chemotherapy (i.e. on the same day)
  5. Previous invasive carcinoma <3 years prior to study entry
  6. Cardiac condition contra-indicating large volume venesection (i.e., active angina or cardiac failure)
  7. Current treatment with another investigational medicinal (chemotherapeutic) product or participation in another investigational therapeutic (chemotherapy)study, at any time during the treatment period and 30 days preceding study entry.
  8. Life expectancy <12 weeks
  9. Unwilling or unable to provide written informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01907009


Contacts
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Contact: Jonathan Shamash, MD FRCP 02034657108 jonathan.shamash@bartshealth.nhs.uk

Locations
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United Kingdom
St Batholowmew's Hospital NHS Recruiting
London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
Barts & The London NHS Trust
Investigators
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Principal Investigator: Jonathan Shamash, MD FRCP Barts & The London NHS Trust
Publications:
[1] Farrugia D, Ansell W, Singh M, Philp T, Chinegwundoh F, Oliver RT. Stilboestrol plus adrenal suppression as salvage treatment for patients failing treatment with luteinizing hormone-releasing hormone analogues and orchidectomy. BJU International 2000; 8:1069-1073. [2] Nishimura K, Nonomura N, Yasunaga Y, Takaha N, Inoue H, Sugao H, Yamaguchi S, Ukimura O, Miki T, Okuyama A. Low doses of oral dexamethasone for hormone-refractory prostate carcinoma. Cancer 2000; 15:2570-6 [3] Shamash J, Dancey G, Barlow C, Wilson P, Ansell W, Oliver RTD. Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding. British Journal of Cancer (2005) 92, 36-40 [4] Melphalan and whole blood stem cell re-infusion in the management of castration-resistant prostate cancer - J Shamash, J Jacob, T Powles, S Agrawal, K Mutsvangwa, N Saunders , P Wilson and J Stebbing [ASCO 2011] [5] Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. J Clin Oncol. 2008 Jan 10;26(2):242-5. [6] A'Hern, R. P. A. 2001. 'Sample size tables for exact single-stage phase II designs.' Statistics in Medicine, Volume 20, pages 859-866. [7] Scher H.I et al (2008). Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: Recommendations of the prostrate cancer clinical trials working group. Journal of clinical oncology 26 (7): 1148-1159.

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Responsible Party: Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT01907009    
Obsolete Identifiers: NCT02349347
Other Study ID Numbers: MEL-CAP
First Posted: July 24, 2013    Key Record Dates
Last Update Posted: September 9, 2015
Last Verified: July 2013
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Melphalan
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic