Study of Minnelide™ in Patients With Advanced GI Tumors

NCT01927965 | Completed Phase 1

• 1 other identifier: Minnelide™ 001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this study is to determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™ and to establish the dose of Minnelide™ recommended for future phase 2 protocol

Conditions

Advanced Gastrointestinal Tumors

Keywords

gastrointestinal tract; GI tract; advanced gastrointestinal tumors; gastrointestinal tumors; GI tumors; biliary; gallbladder,; colorectal,; gastric,; hepatocellular; esophageal; pancreatic

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of Minnelide™

  The MTD will be determined using a 3 + 3 design and will continue until 2 patients at any dose level experience a DLT. A DLT will be defined as Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or infection;Grade 4 thrombocytopenia (or Grade 3 with bleeding);Grade 3 or 4 treatment-related non-hematological toxicity (Grade 3 nausea, vomiting or diarrhea that last \> 72 hours despite maximal treatment constitutes a DLT, insufficient treatment will not constitute an exception to the DLT criteria, as this would constitute inadequate conduct of the study); Dosing delay greater than 2 weeks due to treatment-emergent AEs or related severe laboratory abnormalities.

  24 months

• To establish the dose of Minnelide™ recommended for future phase 2 protocol

  Once the MTD has been determined this will be the dose going forward in phase 2 studies

  24 months

Secondary Outcomes (3)

• To determine the pharmacokinetics of Minnelide™

  24 months

• To observe patients for any evidence of antitumor activity of Minnelide™ per RECIST criteria

  24 months

• To determine pharmacodynamic effect of Minnelide™ on HSP70 levels. And to explore pharmacodynamics effect of Minnelide™ on PET Scans and using Choi criteria on the CT scans.

  24 months

Study Arms (1)

Minnelide™ 001

EXPERIMENTAL

A Phase 1, Multi-Center, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™ given daily for 21 days followed by 7 days off schedule in patients with Advanced GI Tumors

Drug: Minnelide™ 001

Interventions

Minnelide™ 001 DRUG

Minnelide™ will be given as a single agent intravenously as a 30-minute infusion daily x 21 days followed by a 7-day rest period. One cycle will equal 28 days.

Also known as: Minnelide

Minnelide™ 001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed gastrointestinal (GI) carcinoma, which has progressed on standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy), for which effective therapy is not available or for which patients are not a candidate for or intolerant of such therapies.
• Have one or more metastatic tumors measurable on CT scan or locally advanced measurable disease that has clearly progressed after prior treatment per RECIST criteria.
• Male and female patients at least 18 years of age
• Laboratory data as specified:
• Hematology: ANC \>1500 cells/mm3, platelet count \> 150,000 cells/mm3 and Hemoglobin \> 9 g/dL
• Hepatic: Direct bilirubin ≤1.5 X ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 X ULN. For patients with known liver metastases or liver neoplasms, then ALT or AST ≤ 5.0 X ULN is allowed
• Renal: serum creatinine WNL or calculated creatinine clearance ≥ 50 mL/min/1.73m2 for patients with creatinine levels above institutional normal
• Urinalysis: No clinically significant abnormalities
• Coagulation: INR within normal limits, PTT within normal limits
• Estimated life expectancy of at least 3 months
• Karnofsky Performance ≥ 70%
• A negative serum pregnancy test (if female)
• For men and women of child-producing potential - willingness to employ appropriate contraceptive methods (including abstinence) during the study.
• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments.

You may not qualify if:

• Women who are pregnant or nursing. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
• Baseline QTc exceeding 450 msec (470 msec for females) using the Bazetts formula and/or patients receiving class 1A or class III antiarrythmic agents.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Treatment with radiotherapy, chemotherapy or investigational therapy within 1 month (or 5 half lifes for cytotoxics) prior to study entry (6 weeks for nitrosoureas or Mitomycin C).
• Known HIV, Hepatitis A, B or Hepatitis C infection
• Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
• Participation in concurrent study of an investigational agent or device.
• Unwillingness or inability to comply with procedures required in this protocol.
• Any other condition including but not limited to major co-morbidities, which in the opinion of the investigator would render the patient ineligible.

Sponsors & Collaborators

• Minneamrita Therapeutics LLC: lead

Study Sites (2)

Virginia G. Piper Cancer Center at Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

University of Minnesota Masonic Cancer Clinic

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (9)

• Antonoff MB, Chugh R, Borja-Cacho D, Dudeja V, Clawson KA, Skube SJ, Sorenson BS, Saltzman DA, Vickers SM, Saluja AK. Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo. Surgery. 2009 Aug;146(2):282-90. doi: 10.1016/j.surg.2009.04.023.

  PMID: 19628086 BACKGROUND

• Carter BZ, Mak DH, Schober WD, McQueen T, Harris D, Estrov Z, Evans RL, Andreeff M. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood. 2006 Jul 15;108(2):630-7. doi: 10.1182/blood-2005-09-3898. Epub 2006 Mar 23.

  PMID: 16556893 BACKGROUND

• Choi YJ, Kim TG, Kim YH, Lee SH, Kwon YK, Suh SI, Park JW, Kwon TK. Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells. Biochem Pharmacol. 2003 Jul 15;66(2):273-80. doi: 10.1016/s0006-2952(03)00282-x.

  PMID: 12826269 BACKGROUND

• Liu Q, Chen T, Chen H, Zhang M, Li N, Lu Z, Ma P, Cao X. Triptolide (PG-490) induces apoptosis of dendritic cells through sequential p38 MAP kinase phosphorylation and caspase 3 activation. Biochem Biophys Res Commun. 2004 Jul 2;319(3):980-6. doi: 10.1016/j.bbrc.2004.04.201.

  PMID: 15184078 BACKGROUND

• Phillips PA, Dudeja V, McCarroll JA, Borja-Cacho D, Dawra RK, Grizzle WE, Vickers SM, Saluja AK. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 2007 Oct 1;67(19):9407-16. doi: 10.1158/0008-5472.CAN-07-1077.

  PMID: 17909050 BACKGROUND

• Shamon LA, Pezzuto JM, Graves JM, Mehta RR, Wangcharoentrakul S, Sangsuwan R, Chaichana S, Tuchinda P, Cleason P, Reutrakul V. Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 1997 Jan 15;112(1):113-7. doi: 10.1016/S0304-3835(96)04554-5.

  PMID: 9029176 BACKGROUND

• Tengchaisri T, Chawengkirttikul R, Rachaphaew N, Reutrakul V, Sangsuwan R, Sirisinha S. Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters. Cancer Lett. 1998 Nov 27;133(2):169-75. doi: 10.1016/s0304-3835(98)00222-5.

  PMID: 10072166 BACKGROUND

• Wang X, Matta R, Shen G, Nelin LD, Pei D, Liu Y. Mechanism of triptolide-induced apoptosis: Effect on caspase activation and Bid cleavage and essentiality of the hydroxyl group of triptolide. J Mol Med (Berl). 2006 May;84(5):405-15. doi: 10.1007/s00109-005-0022-4. Epub 2005 Dec 30.

  PMID: 16385419 BACKGROUND

• Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, Yang J, Underhill CB, Zhang L. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther. 2003 Jan;2(1):65-72.

  PMID: 12533674 BACKGROUND

Related Links

• Translational Drug Development (TD2)

MeSH Terms

Conditions

Digestive System Neoplasms

Interventions

14-O-phosphonooxymethyltriptolide disodium salt

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases

Study Officials

• Mohana Velagapudi, MD

  Minneamrita Therapeutics LLC

  STUDY DIRECTOR

• Linda Vocila, BSN

  Translational Drug Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 23, 2013
• Study Start: August 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 6, 2017

Record last verified: 2017-03

Locations

US (2)