Study of gp75 Vaccine in Patients With Stage III and IV Melanoma

Malignant Melanoma Clinical Trial

Official title:

Phase I Study of gp75 DNA Vaccine in Patients With AJCC Stage III and IV Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00034554
• Other study ID #: CP09-0001
• Status: Completed
• Phase: Phase 1
• First received: April 30, 2002
• Last updated: April 8, 2010
• Start date: March 2002
• Est. completion date: September 2004

Study information

• Verified date: December 2009
• Source: ImClone LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Up to 24 patients with stage III or stage IV melanoma will be enrolled. Patients who are currently disease-free but at high risk for relapse are also eligible. Patients will receive vaccinations of gp75 at assigned dose levels. Patients who exhibit serologic and stable/clinical response are eligible to receive booster vaccinations. Patients will be evaluated for safety and efficacy throughout the duration of the study. In this study, the optimal biologically effective dose is defined as the lowest dose of gp75 that results in the production of anti-gp75 antibodies.

Description:

This study is designed to evaluate the safety and feasibility of intramuscular vaccination with gp75 DNA in patients with stage III or IV melanoma. Secondary objectives are to observe the patient for any evidence of anti-tumor response and to establish the optimal biologically effective dose. Up to 24 evaluable patients with stage III or IV metastatic melanoma or with stage III melanoma, currently disease-free, but at high risk for recurrence will be enrolled. Patients will be be enrolled into an assigned dose group and will receive five vaccinations of gp75. In order for dose escalation to proceed, only one patient in the current dose group may have demonstrated a dose limiting toxicity (DLT). If a second patient experiences such toxicity then both patients will move down to the previous dose level, and the previous dose level will be considered to be the MTD. If no DLTs are encountered, patients will continue on study at the assigned dose level. Any patient experiencing a DLT will not receive further vaccination until the toxicity has resolved. Patients exhibiting both serological and stable/clinical response after receiving the fifth vaccination will be eligible to receive booster vaccinations. An additional patient will be accrued to the dose level for every patient that progresses prior to the fifth vaccination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 2004
• Est. primary completion date: September 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The patient has a diagnosis of American Joint Commission on Cancer (AJCC) stage 111 or IV malignant melanoma. A patient who is free of disease after surgical resection of stage 111 or IV disease, but at high risk (defined as a primary tumor >4 rnm, satellite or in-transit lesions, one or more positive lymph nodes or distant metastases) for recurrence is also eligible. A patient with metastatic disease may have no more than five sites of disease. The skin represents one site regardless of the number of lesions. Stage 111 melanoma is defined as a pT4 primary tumor (>4m in depth or Clark level 5) in-transit metastases, satellites lesions or regional lymph nodes involved with melanoma.Pathology slides must be reviewed by the investigational site's Department of Pathology.

2. The patient's Karnofsky performance status is 280 at study entry.

3. The patient has given signed informed consent.

4. The patient has had surgery for their melanoma at least 6 months prior to study entry, or has had prior interferon therapy, or developed unacceptable toxicities to interferon therapy, or has a pre-existing condition(s) that precludes the patient fkom receiving interferon treatment.

5. The patient is 21 8 years of age.

6. The patient must have completed any prior irradiation, chemotherapy, or systemic immunotherapy (interferon-alpha, or interleukin-2) at least 30 days prior to study entry.

7. The patient has adequate hematologic function as defined as a platelet count 2100,000/mm3 and white blood cell (WBC) level 23,000/mm3.

8. The patient has serum lactose dehydrogenase (LDH) within normal range and a serum creatinine level <2.0 mg/dL.

9. The patient agrees to use effective contraception if procreative potential exists.

Exclusion Criteria:

1. The patient has stage I11 disease otherwise eligible to receive standard of care melanoma therapy.

2. The patient has a medical condition or use of medication (eg, corticosteroids) that might make it difficult for the patient to complete the full course of treatments or to respond immunologically to them, in the opinion of the investigator.

3. The patient has received irradiation, chemotherapy, or systemic immunotherapy (interferon-alpha, or interleukin-2) within 30 days prior to study entry.

4. The patient is pregnant (confirmed by serum beta human chorionic gonadotropin [PHCG], if applicable) or is breast feeding.

5. The patient has received any investigational agents within 30 days of study entry.

6. The patient has received prior cancer vaccine therapy.

7. The patient has evidence of central nervous system (CNS) metastasis.

8. The patient has evidence of an ocular abnormality, as detected by a slit-lamp ophthalmologic examination, within 4 weeks prior to study entry.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Biological:
• gp75 DNA vaccine
6 patients will be enrolled in each of the 5 vaccination groups. Patients in vaccination groups 1-3 will receive a total of 5(1 mL) vaccinations. Patients assigned to vaccination group 4 will receive a total of 5 (2.0 mL) vaccinations administered as 2 1 mL injections. Patients assigned to vaccination group 5 will receive a total of 5 (4.0 mL or 8.0 mg)vaccinations administered as 4 1 mL injections per vaccination treatment Patients will receive gp75 DNA vaccinations every 3 weeks for 5 vaccinations. Injection sites will be given intramuscularly and rotated for each dose using all 4 limbs with the exception of a site that had the removal of lymph nodes. Progression to next higher dose level will be based on the 5* patient safely completing the 2nd vaccination at the lower dose level.

Locations

Country	Name	City	State
United States	ImClone Investigational Site	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
ImClone LLC	Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (18)

Bakker AB, Schreurs MW, de Boer AJ, Kawakami Y, Rosenberg SA, Adema GJ, Figdor CG. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med. 1994 Mar 1;179(3):1005-9. — View Citation

Bowne WB, Srinivasan R, Wolchok JD, Hawkins WG, Blachere NE, Dyall R, Lewis JJ, Houghton AN. Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med. 1999 Dec 6;190(11):1717-22. — View Citation

Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV. CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med. 1997 Nov 17;186(10):1623-31. — View Citation

Eton O, Legha SS, Balch CM. Cutaneous melanoma. N Engl J Med. 1992 Jan 30;326(5):345-6; author reply 346-7. — View Citation

Hamilton WB, Helling F, Lloyd KO, Livingston PO. Ganglioside expression on human malignant melanoma assessed by quantitative immune thin-layer chromatography. Int J Cancer. 1993 Feb 20;53(4):566-73. — View Citation

Hara I, Nguyen H, Takechi Y, Gansbacher B, Chapman PB, Houghton AN. Rejection of mouse melanoma elicited by local secretion of interleukin-2: implicating macrophages without T cells or natural killer cells in tumor rejection. Int J Cancer. 1995 Apr 10;61(2):253-60. — View Citation

Huygen K, Content J, Denis O, Montgomery DL, Yawman AM, Deck RR, DeWitt CM, Orme IM, Baldwin S, D'Souza C, Drowart A, Lozes E, Vandenbussche P, Van Vooren JP, Liu MA, Ulmer JB. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine. Nat Med. 1996 Aug;2(8):893-8. — View Citation

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9. — View Citation

Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996 Jan;14(1):7-17. — View Citation

Schuchter L, Schultz DJ, Synnestvedt M, Trock BJ, Guerry D, Elder DE, Elenitsas R, Clark WH, Halpern AC. A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group. Ann Intern Med. 1996 Sep 1;125(5):369-75. — View Citation

Sun WH, Burkholder JK, Sun J, Culp J, Turner J, Lu XG, Pugh TD, Ershler WB, Yang NS. In vivo cytokine gene transfer by gene gun reduces tumor growth in mice. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2889-93. — View Citation

Ugen KE, Nyland SB, Boyer JD, Vidal C, Lera L, Rasheid S, Chattergoon M, Bagarazzi ML, Ciccarelli R, Higgins T, Baine Y, Ginsberg R, Macgregor RR, Weiner DB. DNA vaccination with HIV-1 expressing constructs elicits immune responses in humans. Vaccine. 1998 Nov;16(19):1818-21. — View Citation

Vijayasaradhi S, Doskoch PM, Wolchok J, Houghton AN. Melanocyte differentiation marker gp75, the brown locus protein, can be regulated independently of tyrosinase and pigmentation. J Invest Dermatol. 1995 Jul;105(1):113-9. — View Citation

Wang R, Doolan DL, Le TP, Hedstrom RC, Coonan KM, Charoenvit Y, Jones TR, Hobart P, Margalith M, Ng J, Weiss WR, Sedegah M, de Taisne C, Norman JA, Hoffman SL. Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. Science. 1998 Oct 16;282(5388):476-80. — View Citation

Wang RF, Appella E, Kawakami Y, Kang X, Rosenberg SA. Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes. J Exp Med. 1996 Dec 1;184(6):2207-16. — View Citation

Wang RF, Robbins PF, Kawakami Y, Kang XQ, Rosenberg SA. Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31-restricted tumor-infiltrating lymphocytes. J Exp Med. 1995 Feb 1;181(2):799-804. Erratum in: J Exp Med 1995 Mar 1;181(3):1261. — View Citation

Weber LW, Bowne WB, Wolchok JD, Srinivasan R, Qin J, Moroi Y, Clynes R, Song P, Lewis JJ, Houghton AN. Tumor immunity and autoimmunity induced by immunization with homologous DNA. J Clin Invest. 1998 Sep 15;102(6):1258-64. — View Citation

Wolchok JD, Livingston PO, Houghton AN. Vaccines and other adjuvant therapies for melanoma. Hematol Oncol Clin North Am. 1998 Aug;12(4):835-48, vii. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety and feasibility of intramuscular vaccination with gp75 DNA in patients with stage III or IV melanoma.			Yes
Secondary	Observe patients for any evidence of anti-tumor response, which is generated after vaccination.			No
Secondary	Establish the optimal biologically effective dose, defined as the lowest dose that correlates the production of anti-gp75 antibodies.			No