CTSU E1305 - "A Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients with Recurrent or Metastatic Head and Neck Cancer"

Treatment Plan    (Supplied Drug:  Bevacizumab)

PHYSICIAN CHOICE OF PLATINUM-DOUBLET REGIMENS (Choose regimen at regist & prior to randomiz)

Regimen 1

Docetaxel:  75mg/m2, IV over 1 hr, Day 1, q 21 days, followed by

Cisplatin:  75mg/m2, IV over 1-2 hrs, Day 1, q 21 days

Prophylactic Ciprofloxacin:  500mg, PO, BID, Days 5-14

Regimen 1 Carbo

Docetaxel:  75mg/m2, IV over 1 hr, Day 1, q 21 days, followed by

Carboplatin:  AUC 6, over 30 mins, Day 1, q 21 days

Prophylactic Ciprofloxacin:  500mg, PO, BID, Days 5-14

Regimen 2

Cisplatin:  100mg/m2, IV over 1-2 hrs, Day 1, q 21 days, followed by

5-FU:  1000mg/m2, QD, CI, x 4 days, q 21 days

Prophylactic Ciprofloxacin:  500mg, PO, BID, Days 5-14

Regimen 2 Carbo

Carboplatin:  AUC 6, over 30 mins, Day 1, q 21 days, followed by

5-FU:  1000mg/m2, QD, CI, x 4 days, q 21 days

Prophylactic Ciprofloxacin:  500mg, PO, BID, Days 5-14

  â

RANDOMIZATION

  â

Arm A

Platinum-doublet (physician's choice):  Q 21 days, until disease progression

Option to D/C chemo after 6 cycles if maximum response.

Arm B

Bevacizumab:  15mg/kg, IV, Day 1

Platinum-doublet (physician's choice):  Q 21 days, until disease progression

Option to D/C chemo after 6 cycles if maximum response.  Bevacizumab will be continued until progression.

Eligibility

• Histol- or cytol-confirmed squamous cell head & neck cancer (SCCHN), from any primary site (including unknown).  No nasopharyngeal cancer of histol types WHO 2 or 3 or squamous cell cancer originating in skin.

• Must be either:  1) recurrent, judged incurable by surgery or RT or 2) metastatic.  Pts refusing radical resection for recur disease are eligible.  2nd prim SCCHN is allowed if eligibility is based on a recur or mets 1st primary SCCHN.

• No prior chemo or biologic/molecular targeted therapy for recur or mets SCCHN.

  • 1 regimen of induction, concomitant chemoradiotherapy, &/or adjuv chemo as part of initial potential curative therapy is allowed if pt did not receive prior chemo for recur or mets disease.

  • >4 mos between last chemo dose or chemoradiotherapy & study tx.  Must be progression-free >4 mos after completion of chemo/chemoradiotherapy or RT + Cetuximab given w/curative intent.  (Cetuximab therapy:  4 mos between last dose of chemo/chemoradiotherapy & study tx if part of concurrent regimen; 8 wks if part of adjuv regimen post-RT.)

  • No pts who progressed after 2 cycles of induction chemo

• No prior Bevacizumab.

• <1 prior RT regimen, curative or palliative, to head & neck is allowed.  If RT is combined w/chemo &/or Cetuximab, 4 mos must elapse between end of RT & study tx.  If RT given alone, >8 wks must elapse between end of RT & regist.  >3 wks between prior RT to other areas & regist. 

• Not receiving any other investigational agent while on study.

• ECOG perf status 0-1.

• Recovered to >Grade 1 from acute effects of prior surgery, chemo, or RT.  Must be >4 wks post-surgery.  Chronic late xerostomia and speech & swallowing abnormalities from prior RT or surgery are allowed if nutritional status is stable.

• Must have meas disease based on RECIST.  Baseline msmts & eval of all sites of disease w/i 4 wks pe-randomiz.  Disease in prior RT sites is measurable if there is unequivocal disease progression or bx-proven residual carcinoma following RT.  Persistent disease after RT must be bx-proven >8 wks after completion of RT (radiographic findings are allowed if clear-cut msmts can be made).

• <2 wks pre-randomiz:  ANC >1500/mm3; Hgb >8.0g/dL; platelets >100,000/mm3; CrCl >60ml/min (meas or calc by Cockroft-Gault); total bili <INL; SGOT or SGPT & alk phos w/i eligibility range (see protocol table); urine dipstick <0-1+ w/i 14 days of randomiz (if >1+, a UPC ratio is required & must be <1.0 to participate).

• No known brain mets.

• None of following:

  • Tumors invading major vessels as shown unequivocally by imaging studies

  • Central lung mets that are cavitary as shown unequivocally by imaging studies

  • Any prior hx of bleeding related to current head & neck cancer

  • Hx of gross heloptysis (>1/2 teas bright red blood per episode of coughing) <3 mos pre-enrollment

• No prior coagulopathy or hemorrhagic disorders.

• No hx of thrombosis currently requiring therapeutic anticoagulation (prophylactic Warfarin 1mg/day is allowed) & INR <1.5 at regist.

• No chronic daily aspirin >325mg/day or NSAIDs known to inhibit platelet function.  Anti-platelet agents are allowed if pt is not receiving aspirin or NSAIDs known to inhibit platelet function.

• No hypercalcemia related to head & neck cancer.

• No prior non-melanoma skin cancer or in situ cervical cancer unless curatively treated.  Other prior cancers must have been treated w/curative intent & must be disease-free >3 yrs post-dx.

• No current perip neuropathy >Grade 2 at randomiz.

• No co-existing condition to preclude full study compliance.

• No hx of severe hypersensitivity to Docetaxel or other drugs formulated w/polysorbate 80, if physician's choice of chemo is Docetaxel.

• BP <150/90 <2 wks pre-randomiz.  If hx of HTN, it must be <150/90 on a stable regimen of anti-hypertension meds at study entry.

• No major surgery, open bx, or significant traumatic injury w/i 28 days pre-study enrollment.  No anticipated need for major surgery during study course.

• No unstable angina or MI w/i prior 6 mos; no symptomatic CHF (NYHA >Grade II); no hx of aortic dissection or aneurysm >6cm (or at high risk for rupture); no serious cardiac arrhythmia requiring meds (hx of chronic atrial fib/other atrial arrhythmia w/controlled rate on meds is allowed); no clinically significant PVD w/intermittent claudication or need for vascular intervention; no hx of aortic dissection; no hx of CNS cerebrovascular ischemia or stroke w/i past 6 mos; no active serious infection.

• No hx of serious human anti-human antibody reaction.  No known hypersensitivity to Chinese hamster ovary cell products or other recombant human antibodies.

• Age >18.

• No pregnant or nursing women.  Women/Men of reproductive potential must be abstinent or use adequate hormonal/barrier contraception prior to study entry & for duration of study.

• No HIV+ pts receiving combination anti-retroviral therapy.

• No hx of abdominal fistula, GI perforation, or intra-abdominal abscess w/i 6 mos pre-regist.

• PRESTUDY REQUIREMENTS

  <4 wks pre-randomiz:  Scans & xrays used to assess all meas or non-meas sites of disease

  <2 wks pre-randomiz:  CBC/diff/platelets, all chemistries

  • H&P, VS, ht, wt, perf status

  • CBC/diff/platelets

  • Serum creat, K, Na, Cl, CO₂, Ca, Mg

  • Urine dipstick or UPC

  • Total bili, SGOT, SGPT, alk phos

  • CT chest

  • CT or MRI neck

  • EKG

  • PT/PTT (recheck if clinically indicated)

  • Pregnancy test - serum or urine (if applicable; w/i 2 wks pre-randomiz)

  • Tumor msmts (PE, CT, or MRI) - use same method throughout study

  • Correlative/Banking samples (w/pt's consent)*

  *       PE tumor, one 10mL red-top tube serum, two 10mL EDTA purple-top tubes plasma, one 10mL EDTA purple-top tube perip blood, PAXgene DNA tube perip blood, & PAXgene RNA tube perip blood.  Contact KCCOP for kit.

• Signed informed consent.