A Trial of AMG 386 and Temsirolimus in Advanced Solid Tumors
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Purpose
This is a phase 1 study to find out if investigational drug AMG 386, when given by vein at different doses, in combination with temsirolimus, is safe for patients with advanced cancers.This study will also look for the best possible dose for the combination.
| Condition | Intervention | Phase |
|---|---|---|
|
Malignant Solid Tumour |
Drug: AMG 386 Drug: Temsirolimus |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I Trial of AMG 386 and Temsirolimus in Advanced Solid Tumors With an Expansion Cohort in Uterine Cancer, Renal Cell Carcinoma and Carcinoid Tumors |
- Recommended phase II dose (RP2D) and safety profile of AMG 386 in combination with temsirolimus in patients with advanced solid tumors. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]The recommended phase II dose is defined as <1 out of 6 at highest dose level below the maximally administered dose. The safety profile will include the number of participants who experience an adverse event, description of adverse events, grade of events, relationship to the drugs, and frequency of events.
- Levels of certain biomarkers at different timepoints after AMG386 and Temsirolimus are administered. [ Time Frame: 2 years ] [ Designated as safety issue: No ]Tie2 Expressing Monocytes (TEMs), and circulating angiogenic factors (CAFs) and cytokines, including PlGF, SDF-1alpha, sVCAM-1, angiogenin, endostatin, FGF, PDGF, thrombospondin, VEGF, sVEGFR-1,2, and 3, and sESM1.
- Preliminary anti-tumor activity of both drugs when administered at the recommended phase 2 dose to patients with advanced endometrial cancer, renal cell carcinoma, or carcinoid tumor. [ Time Frame: 2 years ] [ Designated as safety issue: No ]Response Evaluation Criteria in Solid Tumors(RECIST) guideline (version 1.1)
| Estimated Enrollment: | 42 |
| Study Start Date: | March 2012 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: AMG 386 and Temsirolimus |
Drug: AMG 386
AMG 386, IV over 60 minutes before Temsirolimus, on Days 1, 8, 15, 22 of every 28 day cycles.
Drug: Temsirolimus
Temsirolimus, IV over 30-60 minutes after AMG 386, on Days 1, 8, 15, 22 of every 28 day cycles.
Other Name: Torisel
|
Detailed Description:
AMG 386 is an intravenous (given by vein) drug that blocks a protein called angiopoietin. As cancers grow they need to develop their own new blood supply to survive and this development of new blood supply vessels is known as angiogenesis. AMG 386 works by slowing or stopping the growth of these new blood vessels which is expected to interfere with the tumor's ability to grow and spread to other parts of the body.
Temsirolimus is an intravenous (given by vein) drug that is commercially available and approved for treatment of some types of kidney cancer. Temsirolimus interferes with a protein in the cell that is part of one pathway that transmits signals to stimulate cell growth and survival. By inhibiting this protein, called mTOR, cancer cells may stop growing or die.
This study has two parts. The first part, called the dose escalation phase, will include patients with any type of solid tumor (a cancer with a tissue mass) to find out the highest dose of AMG386 and temsirolimus that can be given to patients without causing side effects that are too severe. After this dose is found, another group of patients that take part in the study will receive this dose in the second phase called the dose expansion phase. The dose expansion phase of the study will only include patients that have recurrent (the cancer has come back) or metastatic uterine, renal cell, and carcinoid tumors.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Histologically or cytologically confirmed metastatic or unresectable malignancy
- Measurable disease (RECIST version 1.1.)
Prior therapies
- ALL: No prior PI3K-Akt-mTOR inhibitors
- Dose escalation cohorts: No limits
Dose expansion (up to n=12 each ):
- Uterine: At least 1 prior chemo required. Hormones allowed
- Renal: At least one anti-VEGF/R treatment (Rx) required.
- Carcinoid: Long-acting somatostatin analogue allowed. Prior regional Rx for liver mets allowed. Prior anti-VEGF/R Rx allowed
- Age ≥ 18
- ECOG 0-1
- Life expectancy ≥ 12 weeks
- Well controlled blood pressure (BP): ≤140/90 mmHg (anti-hypertension meds allowed)
Normal organ function
- leukocytes ≥3.0 x 109/L
- absolute neutrophil count ≥1.5 x 109/L
- platelets ≥100 x 109/L
- hemoglobin > 90 g/L (or > 9 g/dL)
- total bilirubin ≤ institutional ULN
- AST(SGOT)/ALT(SGPT)≤2.5 X institutional upper limit of normal if no known liver metastasis or ≤5 X institutional upper limit of normal if known liver metastasis
- PTT or aPTT ≤1.5 X ULN per institutional laboratory range and INR ≤1.5
- creatinine ≤ institutional ULN OR >40 mL/min per 24 h urine collection or calculated according to the Cockcroft-Gault formula
- urinary protein ≤30 mg/dL in urinalysis or ≤1+ on dipstick, unless quantitative protein is <1000 mg in a 24 h urine sample
Exclusion Criteria:
- History of CNS metastases
- History of arterial or venous thromboembolism ≤ 12 months
- Therapeutic anticoagulation (neither with LMWH nor warfarin)
- Clinically significant bleeding ≤ 6 months
- Clinically significant cardiovascular disease
- Major surgery ≤ 28 days
- Current of previous treatment with AMG 386 or other angiopoietins or TIE2 receptor inhibitors
- Minor surgery ≤ 3 days (7 days if prior VEGF inhibitor)
- Prior (≤ 4 weeks) chemo- or radiotherapy
- Prior treatment (≤ 30 days) with immunomodulators
- Patients who have not yet completed prior Rx at least 21 days (30 days prior for mAbs)
- Non-healing wound, ulcer, fracture
- Uncontrolled intercurrent illness
- Pregnant women/subjects not consenting for double-barrier contraception
- Not recovery from prior Grade ≥2 toxicities (NCI CTC v4.0)
- Strong inducers or inhibitors of CYP3A4
- Pre-existing clinically significant pulmonary infiltrates
Contacts and Locations| Contact: Monika Wizemann, BSc. (Hons) | 416-581-8132 | monika.wizemann@uhn.ca |
| Contact: Meghan Perry, BSc. (Hons) | 416-946-4501 ext 3181 | meghan.perry@uhn.ca |
| Canada, Ontario | |
| Princess Margaret Hospital | Not yet recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Principal Investigator: | Philippe Bedard, M.D. | Princess Margaret Hospital, Canada |
More Information
No publications provided
| Responsible Party: | University Health Network, Toronto |
| ClinicalTrials.gov Identifier: | NCT01548482 History of Changes |
| Other Study ID Numbers: | PJC-008 (NCI 9041) |
| Study First Received: | February 24, 2012 |
| Last Updated: | March 13, 2012 |
| Health Authority: | Canada: Ethics Review Committee Canada: Health Canada United States: Food and Drug Administration |
Keywords provided by University Health Network, Toronto:
|
Malignancies Tumor Cancer Temsirolimus Metastatic Unresectable |
Solid Uterine Renal cell Carcinoid AMG 386 |
Additional relevant MeSH terms:
|
Neoplasms Sirolimus Everolimus Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 23, 2013