A Phase 2 Study of Oral MKC-1 in Patients With Ovarian or Endometrial Cancer

• ClinicalTrials.gov Identifier: NCT00607607
• Recruitment Status: Completed
• First Posted: February 6, 2008
• Last Update Posted: January 20, 2012
• Sponsor: CASI Pharmaceuticals, Inc.
• Information provided by: CASI Pharmaceuticals, Inc.

Study Description

Brief Summary:

Patients will be treated with MKC-1, twice daily for 14 consecutive days every four weeks (a cycle of MKC-1 chemotherapy), until disease progression or unacceptable toxicities. Patients will be stratified to Arm A (ovarian cancer) or Arm B (endometrial cancer), and will receive identical treatment regimens.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Endometrial Cancer	Drug: MKC-1	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Oral MKC-1 Administered Twice Daily for 14 Consecutive Days Every 4 Weeks in Patients With Recurrent or Resistant Epithelial Ovarian Cancer or Advanced Endometrial Cancer
• Study Start Date: January 2008
• Actual Primary Completion Date: June 2011
• Actual Study Completion Date: January 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; Ovarian Cancer Patients	Drug: MKC-1; capsules, provided 125 mg/m2 BID x 14 days in 28 day cycles
Experimental: B; Endometrial Cancer Patients	Drug: MKC-1; capsules, provided 125 mg/m2 BID x 14 days in 28 day cycles

Outcome Measures

Primary Outcome Measures :

1. Tumor response rate (based on tumor measurements according to the RECIST criteria) or CA-125 [ Time Frame: Every 4 to 8 weeks ]

Secondary Outcome Measures :

1. Time to progression [ Time Frame: Time of progression ]
2. Adverse events spontaneously declared by the patients or noted during physical examination and laboratory tests. [ Time Frame: As reported ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Provide written informed consent (and HIPAA authorization for release of protected health information, as applicable) prior to any study related assessments.
2. Histologically confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis, fallopian tube cancers, or endometrial cancer.
3. Age > 18 years at the time of consent.

4. Arm A: Ovarian Cancer Patients:

   • Must have failed at least one prior platinum based and one taxane based chemotherapeutic regimen. [Platinum failure is defined as platinum-refractory (progression while receiving a platinum-containing regimen) or platinum-resistant (disease progression within 6 months from completion of platinum containing regimen)].
   • Have measurable disease according to RECIST or CA 125 criteria according to GCIG (CA-125 value of > 2 xULN).
   • Have no more than 3 prior regimens for their disease.

   Arm B: Endometrial Cancer Patients:

   • Have no more than 3 prior regimens for their disease
   • Have measurable disease according to RECIST.
5. ECOG performance status of 0, 1, or 2.

6. The following laboratory results, within 10 days of MKC-1 administration:

   • Hemoglobin greater than or equal to 90 g/L (9 g/dL)
   • Absolute neutrophil count greater than or equal to 1.5 x 109/L
   • Platelet count greater than or equal to 100 x 109/L
   • Serum creatinine less than or equal to 1.5 x ULN (upper limit of normal)
   • AST less than or equal to 2.5 x ULN
   • Serum Albumin greater than or equal to 30 g/L (3.0 g/dL)
   • Total bilirubin less than or equal to ULN

Exclusion Criteria:

1. Administration of cancer specific therapy within the following periods prior to study drug initiation:

   • chemotherapy less than 3 weeks prior;
   • hormonal therapy less than one week prior;
   • radiation therapy less than 2 weeks prior.
2. Requirement for paracentesis > 2 liters/week.
3. Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile, or they must agree to use a physical method of contraception. Female patient with childbearing potential must have a negative pregnancy test within 10 days before the first MKC-1 administration.
4. Known CNS metastases unless treated, clinically stable, and not requiring steroids.
5. Clinical evidence of significant bowel obstruction, active uncontrolled malabsorption syndromes, or a history of total gastrectomy.
6. Uncontrolled hypercalcemia (serum calcium-corrected > 3 mmol/L [12 mg/dL]).
7. Serious cardiac condition (Class III/IV congestive heart failure according to New York Heart Association classification); documented acute myocardial infarction within the previous 6 months.
8. Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient. These include: infection requiring parenteral or oral anti-infective treatment, any altered mental status, or any psychiatric condition that would interfere with the understanding of the informed consent.
9. Patients with previous malignancies unless free of recurrence for at least 5 years except cured basal cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix.
10. Treatment with antiretroviral therapy metabolized through CYP3A4 (including indinavir, nelfinavir, ritonavir and saquinavir).

Contacts and Locations

Locations

Canada, Ontario

Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada, K7L 5P9

London Health Sciences Centre

London, Ontario, Canada, N6A 4L6

Credit Valley Hospital

Mississauga, Ontario, Canada, L5M 2N1

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada, H2L 4M1

Sponsors and Collaborators

CASI Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Amit Oza, MD; Princess Margaret Hospital, Canada

More Information

• Responsible Party: Carolyn Sidor, MD, MBA, EntreMed, Inc.
• ClinicalTrials.gov Identifier: NCT00607607
• Other Study ID Numbers: MKC-103
• First Posted: February 6, 2008
• Last Update Posted: January 20, 2012
• Last Verified: January 2012

Keywords provided by CASI Pharmaceuticals, Inc.:

ovarian cancer; endometrial cancer

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Uterine Neoplasms; Uterine Diseases